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World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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References References are made to web resources, and related images are from web resources and related websites.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
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Kelly Benoit-Bird
Associate Professor, College of Oceanic and Atmospheric Sciences at Oregon State University
Kelly Benoit-Bird applies acoustics to the study of ecosystems in the open ocean. She has helped develop several new optical and acoustical instruments and has made fundamental acoustical measurements of species ranging from zooplankton to fish, squid, and marine mammals. Benoit-Bird has been named a MacArthur Fellow, has received the Presidential Early Career Award for Scientists and Engineers, and has published in Nature, Marine Biology and the Journal of the Acoustical Society of America. Through her research into how predators target their prey, Benoit-Bird is creating a new understanding of key ecological processes in the ocean.
Flaminia Catteruccia
Associate Professor of Immunology and Infectious Diseases, Harvard School of Public Health
Flaminia Catteruccia is a molecular entomologist specializing in the reproductive biology of Anopheles mosquitoes, the only mosquitoes capable of transmitting human malaria. Searching for a more effective way to reduce the incidence of malaria, Catteruccia is exploring how disruptions to the mosquito mating process could cause them not to successfully reproduce. Her work has received funding from the Wellcome Trust and has appeared in the Proceedings of the National Academy of Sciences, Nature Biotechnology and Malaria Journal. Her focus on the reproductive biology of mosquitoes seeks keys to fighting a disease that still affects hundreds of millions of people around the world.
Sriram Kosuri
Postdoctoral Fellow, Wyss Institute and Harvard Medical School
Sriram Kosuri is developing next-generation DNA synthesis technologies for use in bioengineering. Prior to his work at the Wyss Institute, Kosuri was the first employee at Joule Unlimited, a biofuel startup company working to develop fuels from sunlight using engineered microbes; and co-founded OpenWetWare, a website designed to share information in the biological sciences. He has authored several patents and patent applications related to both biofuels and DNA synthesis technologies, and has published in journals such as Nature Biotechnology and Molecular Systems Biology. The potential applications of the engineered biological products Kosuri is working on span realms from medicine to environment to energy and materials.
Thaddeus Pace
Assistant Professor, Psychiatry and Behavioral Sciences, Emory University School of Medicine
Thaddeus Pace explores endocrine and immune system changes in people who suffer from stress-related psychiatric illness or who have had adverse early life experiences. His investigations have highlighted the potential of compassion meditation and other complementary practices to help individuals exposed to trauma, including patients with PTSD and children in state foster care programs. Pace’s work has been funded by the National Institute of Mental Health and the U.S. Department of Veterans Affairs, and has appeared in Neuroscience, The American Journal of Psychiatry and International Immunopharmacology. His research aims to contribute new approaches to the long-term health and well-being of children and adults in challenging circumstances.
David Rand
Assistant Professor, Psychology Department, Yale University
David Rand focuses on the evolution of human behavior, with a particular emphasis on cooperation, generosity and altruism. His approach combines empirical observations from behavioral experiments with predictions generated by evolutionary game theoretic math models and computer simulations. Rand has been named to Wired magazine’s Smart List 2012 of “50 people who will change the world” as well as the AAAS/Science Program for Excellence in Science, and his work has been featured on the front covers of both Nature and Science and reported widely in the media. Rand seeks answers to why people are willing to help others at a cost to themselves, and what can be done to help solve social dilemmas when they arise.
Giuseppe Raviola
Director of Mental Health at Partners In Health, Director of the Program in Mental Health and Social Change at Harvard Medical School, and Medical Director of Patient Safety and Quality at Children's Hospital Boston
Giuseppe “Bepi” Raviola works to more fully integrate mental health services into global health care efforts. Through research, clinical practice and training in places ranging from Haiti to Rwanda, Raviola is building teams and bridging disciplines to address this critical and previously neglected issue. His ideas and findings have appeared in The Lancet, the Harvard Review of Psychiatry and the Journal of Child Psychology and Psychiatry. Raviola’s work on behalf of local mental health team leaders aims to build lasting, community-based systems of mental health care.
John Rinn
Assistant Professor of Stem Cell and Regenerative Biology at Harvard University and Medical School and Senior Associate Member of the Broad Institute
John Rinn takes an unconventional approach to the way biologists think about the human genome. Focusing on large intervening non-coding RNAs (lincRNAs), his work suggests that so-called “junk genes” may actually play a key regulatory role in cell function. Rinn’s finding have been published in Nature, Science and the Proceedings of the National Academy of Sciences, and he has been named to Popular Science’s “Brilliant 10.” By identifying thousands of new RNA genes in the human genome, he is working toward a better understanding of their importance for human health and disease.
Leila Takayama
Research Scientist, Willow Garage
Leila Takayama studies how people perceive, understand, feel about and interact with robots. What can robots do? Better yet, what should they do, and how? Takayama has been collaborating with character animators, sound designers, and product designers to work toward making both the appearance and behaviors of robots more human-readable, approachable, and appealing. Her findings have appeared in the International Journal of Design, Neural Networks and IEEE Pervasive Computing. Through her research, Takayama is leading the way toward robots that serve their purposes more effectively and intuitively.
Tiffani Williams
Associate Professor, Computer Science and Engineering, Texas A&M University
Tiffani Williams explores new ways to use computation in helping to reconstruct the phylogenetic ways that all organisms are connected. A specialist in bioinformatics and high-performance computing, she is working with a multidisciplinary team to build the Open Tree of Life, showing the previously established links among species and providing tools for scientists to update and revise the tree as new data come in. She has been a Radcliffe Institute Fellow, has been funded by the National Science Foundation, and has published in Science, Evolutionary Bioinformatics and the Journal of Computational Biology. By helping identify how species are related to each other, Williams is providing a framework for new understanding in realms such as ecological health, environmental change, and human disease.
Benjamin Zaitchik
Assistant Professor, Department of Earth and Planetary Sciences, Johns Hopkins University
Benjamin Zaitchik’s research is directed at understanding, managing, and coping with climatic and hydrologic variability. He looks for new approaches to controlling human influences on climate and water resources at local, regional and global scales, and explores improved forecast systems and methods of risk assessment. His work has received funding from NASA, the National Institutes of Health and the National Science Foundation, and appeared in the International Journal of Environmental Research and Public Health and Water Resources Research, among others. Zaitchik is interested in helping provide new insights in such crucial areas as transboundary water management, climate-informed disease early warning systems, and adaptation strategies in subsistence agricultural communities.
www.sk.ru/en Boston, USA 18JUN2012
Representatives from the Skolkovo Foundation participated in the 2012 BIO International Convention at the Boston Convention and Exhibition Center June 18-21. The conference, attended by pharmaceutical companies, teaching hospitals, venture capital firms and over 500 biotechnology companies, drew more than 15,000 attendees to the Boston area.
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
* Nouvelle modification de la structure chimique des médicaments contre les coronavirus * Conception et dépistage des médicaments assistés par ordinateur. *"Missile biologique antiviral", "Nouveaux comprimés anti-épidémiques contre le coronavirus", "Liquide oral antiviral composite", "Nouveaux comprimés oraux à action prolongée contre le coronavirus", "Nouveaux inhibiteurs de coronavirus" (injection)
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(leader mondial, scientifique, scientifique médical, biologiste, virologue, pharmacien, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" est un important document de recherche scientifique. Il a maintenant été révisé et réédité par l'auteur original à plusieurs reprises. La compilation est publiée et publiée selon le manuscrit original pour répondre aux besoins des lecteurs et des internautes du monde entier. En même temps, elle est également très bénéfique pour le grand nombre de chercheurs en médicaments cliniques médicaux et de divers experts et universitaires. Nous espérons qu'il sera corrigé dans la réimpression.------Compilé par Jacques Lucy à Genève, août 2021
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Selon les statistiques en temps réel de Worldometer, vers 6h30 le 23 juillet, il y avait un total de 193 323 815 cas confirmés de nouvelle pneumonie coronarienne dans le monde, et un total de 4 150 213 décès. Il y a eu 570 902 nouveaux cas confirmés et 8 766 nouveaux décès dans le monde en une seule journée. Les données montrent que les États-Unis, le Brésil, le Royaume-Uni, l'Inde et l'Indonésie sont les cinq pays avec le plus grand nombre de nouveaux cas confirmés, et l'Indonésie, le Brésil, la Russie, l'Afrique du Sud et l'Inde sont les cinq pays avec le plus grand nombre de nouveaux décès.
Les nouvelles souches de coronavirus et de mutants delta ont été particulièrement graves ces derniers temps. De nombreux pays et lieux ont repris vie et le nombre de cas n'a pas diminué, mais a augmenté.
, Il est digne de vigilance. Bien que de nombreux pays aient renforcé la prévention et le contrôle des vaccins et d'autres mesures de prévention et de contrôle, il existe encore de nombreuses lacunes et carences dans la suppression et la prévention du virus. Le nouveau coronavirus et diverses souches mutantes présentent un certain degré d'antagonisme par rapport aux médicaments traditionnels et à la plupart des vaccins. Bien que la plupart des vaccins aient de grandes propriétés anti-épidémiques et aient des effets et une protection importants et irremplaçables pour la prévention et le traitement, il est impossible d'empêcher complètement la propagation et l'infection des virus. La propagation de la nouvelle pneumonie à virus couronne a été retardée de près de deux ans. Il y a des centaines de millions de personnes infectées dans le monde, des millions de décès, et le temps est long, la propagation est généralisée et des milliards de personnes dans le monde sont parmi Les dommages causés par le virus sont assez terribles, c'est bien connu. Plus urgent
Ce qui est plus grave, c'est que le virus et les souches mutantes n'ont pas complètement reculé, surtout que de nombreuses personnes sont encore infectées et infectées après avoir été injectées avec divers vaccins.L'efficacité du vaccin et la résistance du virus mutant sont dignes des scientifiques médicaux, virologues , les pharmacologues Les zoologistes et autres réfléchissent et analysent sérieusement. La situation épidémique actuelle dans les pays européens et américains, la Chine, le Brésil, l'Inde, les États-Unis, la Russie et d'autres pays s'est considérablement améliorée par rapport à l'année dernière.Cependant, les chiffres pertinents montrent que la situation épidémique mondiale ne s'est pas complètement améliorée, et certains pays et régions sont encore très graves. En particulier, après une utilisation intensive de divers vaccins, des cas surviennent encore, et dans certains endroits ils sont encore très graves, ce qui mérite une grande vigilance. Les mesures de prévention et de contrôle sont très importantes.De plus, les vaccins et divers médicaments antiépidémiques sont les premiers choix nécessaires, et les autres méthodes sont irremplaçables. Il est particulièrement important de développer et de développer des médicaments complets, des médicaments antiviraux, des médicaments immunitaires et des médicaments génétiques. Les expériences de recherche sur les nouveaux coronavirus et virus mutants nécessitent une analyse plus rigoureuse et approfondie des données, des tissus pathogènes pathologiques, des gènes cellulaires, de la chimie moléculaire, de la chimie quantique, etc., ainsi que de la chimie moléculaire des vaccins, de la physique quantique, de la biologie quantique, de l'histologie cytologique, la chimie médicinale et les médicaments Et les symptômes, l'efficacité, la sécurité, l'efficacité à long terme, etc. du vaccin, bien sûr, y compris des dizaines de milliers de cas cliniques et de décès et d'autres informations et preuves de première main. La tâche de l'ARN (acide ribonucléique) dans le corps humain est d'utiliser les informations de notre matériel génétique ADN pour produire des protéines. Il accomplit cette tâche dans le ribosome, la zone productrice de protéines de la cellule. Le ribosome est le lieu où se produit la biosynthèse des protéines.
La médecine en profite : dans la vaccination, l'ARNm produit artificiellement fournit aux ribosomes des instructions pour construire des antigènes pathogènes contre lesquels lutter, par exemple, la protéine de pointe du coronavirus.
Les vaccins vivants traditionnels ou les vaccins inactivés contiennent des antigènes qui provoquent la réaction du système immunitaire. Le vaccin à ARNm est produit dans la cellule
(1) La spécificité des nouveaux coronavirus et virus mutants, etc., virologie et chimie quantique des virus mutants, physique quantique, microbiologie quantique
(2) Nouvelle conception de vaccin couronne, biologie moléculaire et structure chimique, etc.
(3) La généralité et la particularité du développement de nouveaux médicaments contre le coronavirus
(4) Diverses conceptions de médicaments pour la pneumonie à nouveau coronavirus, la chimie médicinale, la pharmacologie, etc., les cellules, les protéines, l'ADN, la chimie des enzymes, la chimie quantique pharmaceutique, la physique quantique pharmaceutique, la biochimie humaine, la biophysique humaine, etc.
(5) Les caractéristiques d'évolution et de mutation du nouveau coronavirus et de divers virus mutants, la nature à long terme, la répétabilité, la résistance aux médicaments et la résistance épidémique du virus, etc.
(6) Pneumonie à nouveau coronavirus et transmission infectieuse de divers nouveaux coronavirus et leurs particularités
(7) La transmission invisible de la pneumonie à nouveau coronavirus et de divers virus mutants chez l'homme ou l'animal, et la symbiose mutuelle de l'infection croisée de diverses bactéries et virus sont également l'une des causes très graves de dommages graves aux nouveaux coronavirus et virus mutants. La virologie, la pathologie, l'étiologie, le séquençage des gènes, la cartographie des gènes et un grand nombre d'études analytiques ont montré qu'il existe de nombreux cas en Chine, aux États-Unis, en Inde, en Russie, au Brésil et dans d'autres pays.
(8) Pour la prévention et le traitement symptomatiques du nouveau coronavirus, la combinaison de divers vaccins et de di
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World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
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Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
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L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
World leader, international leader, scientist, medical scientist, virologist, philosopher, thinker, cosmologist, sociologist, and Professor Fangruida
World leader, scientist, medical scientist, virologist, pharmacist, Professor Fangruida (F.D Smith) on the world epidemic and the nemesis and prevention of new coronaviruses and mutant viruses (Jacques Lucy) 2021v1.5)
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The Nemesis and Killer of New Coronavirus and Mutated Viruses-Joint Development of Vaccines and Drugs (Fangruida) July 2021
*The particularity of new coronaviruses and mutant viruses*The broad spectrum, high efficiency, redundancy, and safety of the new coronavirus vaccine design and development , Redundancy and safety
*New coronavirus drug chemical structure modification*Computer-aided design and drug screening. *"Antiviral biological missile", "New Coronavirus Anti-epidemic Tablets", "Composite Antiviral Oral Liquid", "New Coronavirus Long-acting Oral Tablets", "New Coronavirus Inhibitors" (injection)
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(World leader, scientist, medical scientist, biologist, virologist, pharmacist, FD Smith) "The Nemesis and Killer of New Coronavirus and Mutated Viruses-The Joint Development of Vaccines and Drugs" is an important scientific research document. Now it has been revised and re-published by the original author several times. The compilation is published and published according to the original manuscript to meet the needs of readers and netizens all over the world. At the same time, it is also of great benefit to the vast number of medical clinical drug researchers and various experts and scholars. We hope that it will be corrected in the reprint.------Compiled by Jacques Lucy in Geneva, August 2021
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According to Worldometer's real-time statistics, as of about 6:30 on July 23, there were a total of 193,323,815 confirmed cases of new coronary pneumonia worldwide, and a total of 4,150,213 deaths. There were 570,902 new confirmed cases and 8,766 new deaths worldwide in a single day. Data shows that the United States, Brazil, the United Kingdom, India, and Indonesia are the five countries with the largest number of new confirmed cases, and Indonesia, Brazil, Russia, South Africa, and India are the five countries with the largest number of new deaths.
The new coronavirus and delta mutant strains have been particularly serious in the recent past. Many countries and places have revived, and the number of cases has not decreased, but has increased.
, It is worthy of vigilance. Although many countries have strengthened vaccine prevention and control and other prevention and control measures, there are still many shortcomings and deficiencies in virus suppression and prevention. The new coronavirus and various mutant strains have a certain degree of antagonism to traditional drugs and most vaccines. Although most vaccines have great anti-epidemic properties and have important and irreplaceable effects and protection for prevention and treatment, it is impossible to completely prevent the spread and infection of viruses. The spread of the new crown virus pneumonia has been delayed for nearly two years. There are hundreds of millions of people infected worldwide, millions of deaths, and the time is long, the spread is widespread, and billions of people around the world are among them. The harm of the virus is quite terrible. This is well known. of. More urgent
What is more serious is that the virus and mutant strains have not completely retreated, especially many people are still infected and infected after being injected with various vaccines. The effectiveness of the vaccine and the resistance of the mutant virus are worthy of medical scientists, virologists, pharmacologists Zoologists and others seriously think and analyze. The current epidemic situation in European and American countries, China, Brazil, India, the United States, Russia and other countries has greatly improved from last year. However, relevant figures show that the global epidemic situation has not completely improved, and some countries and regions are still very serious. In particular, after extensive use of various vaccines, cases still occur, and in some places they are still very serious, which deserves a high degree of vigilance. Prevention and control measures are very important. In addition, vaccines and various anti-epidemic drugs are the first and necessary choices, and other methods are irreplaceable. It is particularly important to develop and develop comprehensive drugs, antiviral drugs, immune drugs, and genetic drugs. Research experiments on new coronaviruses and mutant viruses require more rigorous and in-depth data analysis, pathological pathogenic tissues, cell genes, molecular chemistry, quantum chemistry, etc., as well as vaccine molecular chemistry, quantum physics, quantum biology, cytological histology, medicinal chemistry, and drugs And the vaccine’s symptomatic, effectiveness, safety, long-term effectiveness, etc., of course, including tens of thousands of clinical cases and deaths and other first-hand information and evidence. The task of RNA (ribonucleic acid) in the human body is to use the information of our genetic material DNA to produce protein. It accomplishes this task in the ribosome, the protein-producing area of the cell. The ribosome is the place where protein biosynthesis occurs.
Medicine takes advantage of this: In vaccination, artificially produced mRNA provides ribosomes with instructions for constructing pathogen antigens to fight against—for example, the spike protein of coronavirus.
Traditional live vaccines or inactivated vaccines contain antigens that cause the immune system to react. The mRNA vaccine is produced in the cell
(1) The specificity of new coronaviruses and mutant viruses, etc., virology and quantum chemistry of mutant viruses, quantum physics, quantum microbiology
(2) New crown vaccine design, molecular biology and chemical structure, etc.
(3) The generality and particularity of the development of new coronavirus drugs
(4) Various drug design for new coronavirus pneumonia, medicinal chemistry, pharmacology, etc., cells, proteins, DNA, enzyme chemistry, pharmaceutical quantum chemistry, pharmaceutical quantum physics, human biochemistry, human biophysics, etc.
(5) The evolution and mutation characteristics of the new coronavirus and various mutant viruses, the long-term nature, repeatability, drug resistance, and epidemic resistance of the virus, etc.
(6) New coronavirus pneumonia and the infectious transmission of various new coronaviruses and their particularities
(7) The invisible transmission of new coronavirus pneumonia and various mutant viruses in humans or animals, and the mutual symbiosis of cross infection of various bacteria and viruses are also one of the very serious causes of serious harm to new coronaviruses and mutant viruses. Virology, pathology, etiology, gene sequencing, gene mapping, and a large number of analytical studies have shown that there are many cases in China, the United States, India, Russia, Brazil, and other countries.
(8) For the symptomatic prevention and treatment of the new coronavirus, the combination of various vaccines and various antiviral drugs is critical.
(9) According to the current epidemic situation and research judgments, the epidemic situation may improve in the next period of time and 2021-2022, and we are optimistic about its success. However, completely worry-free, it is still too early to win easily. It is not just relying on vaccination. Wearing masks to close the city and other prevention and control measures and methods can sit back and relax, and you can win a big victory. Because all kinds of research and exploration still require a lot of time and various experimental studies. It is not a day's work. A simple taste is very dangerous and harmful. The power and migratory explosiveness of viruses sometimes far exceed human thinking and perception. In the future, next year, or in the future, whether viruses and various evolutionary mutation viruses will re-attack, we still need to study, analyze, prevent and control, rather than being complacent, thinking that the vaccine can win a big victory is inevitably naive and ridiculous. Vaccine protection is very important, but it must not be taken carelessly. The mutation of the new crown virus is very rampant, and the cross-infection of recessive and virulent bacteria makes epidemic prevention and anti-epidemic very complicated.
(10) New crown virus pneumonia and the virus's stubbornness, strength, migration, susceptibility, multi-infectiousness, and occult. The effectiveness of various vaccines and the particularity of virus mutations The long-term hidden dangers and repeated recurrences of the new coronavirus
(11) The formation mechanism and invisible transmission of invisible viruses, asymptomatic infections and asymptomatic infections, asymptomatic transmission routes, asymptomatic infections, pathological pathogens. The spread and infection of viruses and mutated viruses, the blind spots and blind spots of virus vaccines, viral quantum chemistry and
The chemical and physical corresponding reactions at the meeting points of highly effective vaccine drugs, etc. The variability of mutated viruses is very complicated, and vaccination cannot completely prevent the spread of infection.
(12) New crown virus pneumonia and various respiratory infectious diseases are susceptible to infections in animals and humans, and are frequently recurring. This is one of the frequently-occurring and difficult diseases of common infectious diseases. Even with various vaccines and various antiviral immune drugs, it is difficult to completely prevent the occurrence and spread of viral pneumonia. Therefore, epidemic prevention and anti-epidemic is a major issue facing human society, and no country should take it lightly. The various costs that humans pay on this issue are very expensive, such as Ebola virus, influenza A virus,
Hepatitis virus,
Marburg virus
Sars coronavirus, plague, anthracnose, cholera
and many more. The B.1.1.7 mutant virus that was first discovered in the UK was renamed Alpha mutant virus; the B.1.351 that was first discovered in South Africa was renamed Beta mutant virus; the P.1 that was first discovered in Brazil was renamed Gamma mutant virus; the mutation was first discovered in India There are two branches of the virus. B.1.617.2, which was listed as "mutated virus of concern", was renamed Delta mutant virus, and B.1.617.1 of "mutated virus to be observed" was renamed Kappa mutant virus.
However, experts in many countries believe that the current vaccination is still effective, at least it can prevent severe illness and reduce deaths.
Delta mutant strain
According to the degree of risk, the WHO divides the new crown variant strains into two categories: worrying variant strains (VOC, variant of concern) and noteworthy variant strains (VOI, variant of interest). The former has caused many cases and a wide range of cases worldwide, and data confirms its transmission ability, strong toxicity, high power, complex migration, and high insidious transmission of infection. Resistance to vaccines may lead to the effectiveness of vaccines and clinical treatments. Decrease; the latter has confirmed cases of community transmission worldwide, or has been found in multiple countries, but has not yet formed a large-scale infection. Need to be very vigilant. Various cases and deaths in many countries in the world are related to this. In some countries, the epidemic situation is repeated, and it is also caused by various reasons and viruses, of course, including new cases and so on.
At present, VOC is the mutant strain that has the greatest impact on the epidemic and the greatest threat to the world, including: Alpha, Beta, Gamma and Delta. , Will the change of the spur protein in the VOC affect the immune protection effect of the existing vaccine, or whether it will affect the sensitivity of the VOC to the existing vaccine? For this problem, it is necessary to directly test neutralizing antibodies, such as those that can prevent the protection of infection. Antibodies recognize specific protein sequences on viral particles, especially those spike protein sequences used in mRNA vaccines.
(13) Countries around the world, especially countries and regions with more severe epidemics, have a large number of clinical cases, severe cases, and deaths, especially including many young and middle-aged patients, including those who have been vaccinated. The epidemic is more complicated and serious. Injecting various vaccines, taking strict control measures such as closing the city and wearing masks are very important and the effect is very obvious. However, the new coronavirus and mutant viruses are so repeated, their pathological pathogen research will also be very complicated and difficult. After the large-scale use of the vaccine, many people are still infected. In addition to the lack of prevention and control measures, it is very important that the viability of the new coronavirus and various mutant viruses is very important. It can escape the inactivation of the vaccine. It is very resistant to stubbornness. Therefore, the recurrence of new coronavirus pneumonia is very dangerous. What is more noteworthy is that medical scientists, virologists, pharmacists, biologists, zoologists and clinicians should seriously consider the correspondence between virus specificity and vaccine drugs, and the coupling of commonality and specificity. Only in this way can we find targets. Track and kill viruses. Only in this sense can the new crown virus produce a nemesis, put an end to and eradicate the new crown virus pneumonia. Of course, this is not a temporary battle, but a certain amount of time and process to achieve the goal in the end.
(14) The development and evolution of the natural universe and earth species, as well as life species. With the continuous evolution of human cell genes, microbes and bacterial viruses are constantly mutated and inherited. The new world will inevitably produce a variety of new pathogens.
And viruses. For example, neurological genetic disease, digestive system disease, respiratory system disease, blood system disease, cardiopulmonary system disease, etc., new diseases will continue to emerge as humans develop and evolve. Human migration to space, space diseases, space psychological diseases, space cell diseases, space genetic diseases, etc. Therefore, for the new coronavirus and mutated viruses, we must have sufficient knowledge and response, and do not think that it will be completely wiped out.
, And is not a scientific attitude. Viruses and humans mutually reinforce each other, and viruses and animals and plants mutually reinforce each other. This is the iron law of the natural universe. Human beings can only adapt to natural history, but cannot deliberately modify natural history.
Active immune products made from specific bacteria, viruses, rickettsiae, spirochetes, mycoplasma and other microorganisms and parasites are collectively called vaccines. Vaccination of animals can make the animal body have specific immunity. The principle of vaccines is to artificially attenuate, inactivate, and genetically attenuate pathogenic microorganisms (such as bacteria, viruses, rickettsia, etc.) and their metabolites. Purification and preparation methods, made into immune preparations for the prevention of infectious diseases. In terms of ingredients, the vaccine retains the antigenic properties and other characteristics of the pathogen, which can stimulate the body's immune response and produce protective antibodies. But it has no pathogenicity and does not cause harm to the body. When the body is exposed to this pathogen again, the immune system will produce more antibodies according to the previous memory to prevent the pathogen from invading or to fight against the damage to the body. (1) Inactivated vaccines: select pathogenic microorganisms with strong immunogenicity, culture them, inactivate them by physical or chemical methods, and then purify and prepare them. The virus species used in inactivated vaccines are generally virulent strains, but the use of attenuated attenuated strains also has good immunogenicity, such as the inactivated polio vaccine produced by the Sabin attenuated strain. The inactivated vaccine has lost its infectivity to the body, but still maintains its immunogenicity, which can stimulate the body to produce corresponding immunity and resist the infection of wild strains. Inactivated vaccines have a good immune effect. They can generally be stored for more than one year at 2～8°C without the risk of reversion of virulence; however, the inactivated vaccines cannot grow and reproduce after entering the human body. They stimulate the human body for a short time and must be strong and long-lasting. In general, adjuvants are required for immunity, and multiple injections in large doses are required, and the local immune protection of natural infection is lacking. Including bacteria, viruses, rickettsiae and toxoid preparations.
(2) Live attenuated vaccine: It is a vaccine made by using artificial targeted mutation methods or by screening live microorganisms with highly weakened or basically non-toxic virulence from the natural world. After inoculation, the live attenuated vaccine has a certain ability to grow and reproduce in the body, which can cause the body to have a reaction similar to a recessive infection or a mild infection, and it is widely used.
(3) Subunit vaccine: Among the multiple specific antigenic determinants carried by macromolecular antigens, only a small number of antigenic sites play an important role in the protective immune response. Separate natural proteins through chemical decomposition or controlled proteolysis, and extract bacteria and virusesVaccines made from fragments with immunological activity are screened out of the special protein structure of, called subunit vaccines. Subunit vaccines have only a few major surface proteins, so they can eliminate antibodies induced by many unrelated antigens, thereby reducing the side effects of the vaccine and related diseases and other side effects caused by the vaccine. (4) Genetically engineered vaccine: It uses DNA recombination biotechnology to direct the natural or synthetic genetic material in the pathogen coat protein that can induce the body's immune response into bacteria, yeast or mammalian cells to make it fully expressed. A vaccine prepared after purification. The application of genetic engineering technology can produce subunit vaccines that do not contain infectious substances, stable attenuated vaccines with live viruses as carriers, and multivalent vaccines that can prevent multiple diseases. This is the second-generation vaccine following the first-generation traditional vaccine. It has the advantages of safety, effectiveness, long-term immune response, and easy realization of combined immunization. It has certain advantages and effects.
New coronavirus drug development, drug targets and chemical modification.
Ligand-based drug design (or indirect drug design planning) relies on the knowledge of other molecules that bind to the target biological target. These other molecules can be used to derive pharmacophore models and structural modalities, which define the minimum necessary structural features that the molecule must have in order to bind to the target. In other words, a model of a biological target can be established based on the knowledge of the binding target, and the model can be used to design new molecular entities and other parts that interact with the target. Among them, the quantitative structure-activity relationship (QSAR) is included, in which the correlation between the calculated properties of the molecule and its experimentally determined biological activity can be derived. These QSAR relationships can be used to predict the activity of new analogs. The structure-activity relationship is very complicated.
Based on structure
Structure-based drug design relies on knowledge of the three-dimensional structure of biological targets obtained by methods such as X-ray crystallography or NMR spectroscopy and quantum chemistry. If the experimental structure of the target is not available, it is possible to create a homology model of the target and other standard models that can be compared based on the experimental structure of the relevant protein. Using the structure of biological targets, interactive graphics and medical chemists’ intuitive design can be used to predict drug candidates with high affinity and selective binding to the target. Various automatic calculation programs can also be used to suggest new drug candidates.
The current structure-based drug design methods can be roughly divided into three categories. The 3D method is to search a large database of small molecule 3D structures to find new ligands for a given receptor, in order to use a rapid approximate docking procedure to find those suitable for the receptor binding pocket. This method is called virtual screening. The second category is the de novo design of new ligands. In this method, by gradually assembling small fragments, a ligand molecule is established within the constraints of the binding pocket. These fragments can be single atoms or molecular fragments. The main advantage of this method is that it can propose novel structures that are not found in any database. The third method is to optimize the known ligand acquisition by evaluating the proposed analogs in the binding cavity.
Bind site ID
Binding site recognition is a step in structure-based design. If the structure of the target or a sufficiently similar homologue is determined in the presence of the bound ligand, the ligand should be observable in that structure, in which case the location of the binding site is small. However, there may not be an allosteric binding site of interest. In addition, only apo protein structures may be available, and it is not easy to reliably identify unoccupied sites that have the potential to bind ligands with high affinity. In short, the recognition of binding sites usually depends on the recognition of pits. The protein on the protein surface can hold molecules the size of drugs, etc. These molecules also have appropriate "hot spots" that drive ligand binding, hydrophobic surfaces, hydrogen bonding sites, and so on.
Drug design is a creative process of finding new drugs based on the knowledge of biological targets. The most common type of drug is small organic molecules that activate or inhibit the function of biomolecules, thereby producing therapeutic benefits for patients. In the most important sense, drug design involves the design of molecules with complementary shapes and charges that bind to their interacting biomolecular targets, and therefore will bind to them. Drug design often but does not necessarily rely on computer modeling techniques. A more accurate term is ligand design. Although the design technology for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, etc., which must be optimized first before the ligand can become safe and effective. drug. These other features are usually difficult to predict and realize through reasonable design techniques. However, due to the high turnover rate, especially in the clinical stage of drug development, in the early stage of the drug design process, more attention is paid to the selection of drug candidates. The physical and chemical properties of these drug candidates are expected to be reduced during the development process. Complications are therefore more likely to lead to the approval of the marketed drug. In addition, in early drug discovery, in vitro experiments with computational methods are increasingly used to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological characteristics. A more accurate term is ligand design. Although the design technique for predicting binding affinity is quite successful, there are many other characteristics, such as bioavailability, metabolic half-life, side effects, iatrogenic effects, etc., which must be optimized first, and then the ligand To become safe and effective.
For drug targets, two aspects should be considered when selecting drug targets:
1. The effectiveness of the target, that is, the target is indeed related to the disease, and the symptoms of the disease can be effectively improved by regulating the physiological activity of the target.
2. The side effects of the target. If the regulation of the physiological activity of the target inevitably produces serious side effects, it is inappropriate to select it as the target of drug action or lose its important biological activity. The reference frame of the target should be expanded in multiple dimensions to have a big choice.
3. Search for biomolecular clues related to diseases: use genomics, proteomics and biochip technology to obtain biomolecular information related to diseases, and perform bioinformatics analysis to obtain clue information.
4. Perform functional research on related biomolecules to determine the target of candidate drugs. Multiple targets or individual targets.
5. Candidate drug targets, design small molecule compounds, and conduct pharmacological research at the molecular, cellular and overall animal levels.
Covalent bonding type
The covalent bonding type is an irreversible form of bonding, similar to the organic synthesis reaction that occurs. Covalent bonding types mostly occur in the mechanism of action of chemotherapeutic drugs. For example, alkylating agent anti-tumor drugs produce covalent bonding bonds to guanine bases in DNA, resulting in cytotoxic activity.
. Verify the effectiveness of the target.
Based on the targets that interact with drugs, that is, receptors in a broad sense, such as enzymes, receptors, ion channels, membranes, antigens, viruses, nucleic acids, polysaccharides, proteins, enzymes, etc., find and design reasonable drug molecules. Targets of action and drug screening should focus on multiple points. Drug intermediates and chemical modification. Combining the development of new drugs with the chemical structure modification of traditional drugs makes it easier to find breakthroughs and develop new antiviral drugs. For example, careful selection, modification and modification of existing related drugs that can successfully treat and recover a large number of cases, elimination and screening of invalid drugs from severe death cases, etc., are targeted, rather than screening and capturing needles in a haystack, aimless, with half the effort. Vaccine design should also be multi-pronged and focused. The broad-spectrum, long-term, safety, efficiency and redundancy of the vaccine should all be considered. In this way, it will be more powerful to deal with the mutation and evolution of the virus. Of course, series of vaccines, series of drugs, second-generation vaccines, third-generation vaccines, second-generation drugs, third-generation drugs, etc. can also be developed. Vaccines focus on epidemic prevention, and medicines focus on medical treatment. The two are very different; however, the two complement each other and complement each other. Therefore, in response to large-scale epidemics of infectious diseases, vaccines and various drugs are the nemesis and killers of viral diseases. Of course, it also includes other methods and measures, so I won't repeat them here.
Mainly through the comprehensive and accurate understanding of the structure of the drug and the receptor at the molecular level and even the electronic level, structure-based drug design and the understanding of the structure, function, and drug action mode of the target and the mechanism of physiological activity Mechanism-based drug design.
Compared with the traditional extensive pharmacological screening and lead compound optimization, it has obvious advantages.
Viral RNA replicase, also known as RNA-dependent RNA polymerase (RdRp) is responsible for the replication and transcription of RNA virus genome, and plays a very important role in the process of virus self-replication in host cells, and It also has a major impact on the mutation of the virus, it will change and accelerate the replication and recombination. Because RdRp from different viruses has a highly conserved core structure, the virus replicase is an important antiviral drug target and there are other selection sites, rather than a single isolated target target such as the new coronavirus As with various mutant viruses, inhibitors developed for viral replicase are expected to become a broad-spectrum antiviral drug. The currently well-known anti-coronavirus drug remdesivir (remdesivir) is a drug for viral replicase.
New antiviral therapies are gradually emerging. In addition to traditional polymerase and protease inhibitors, nucleic acid drugs, cell entry inhibitors, nucleocapsid inhibitors, and drugs targeting host cells are also increasingly appearing in the research and development of major pharmaceutical companies. The treatment of mutated viruses is becoming increasingly urgent. The development of drugs for the new coronavirus pneumonia is very important. It is not only for the current global new coronavirus epidemic, but more importantly, it is of great significance to face the severe pneumonia-respiratory infectious disease that poses a huge threat to humans.
There are many vaccines and related drugs developed for the new coronavirus pneumonia, and countries are vying for a while, mainly including the following:
Identification test, appearance, difference in loading, moisture, pH value, osmolality, polysaccharide content, free polysaccharide content, potency test, sterility test, pyrogen test, bacterial endotoxin test, abnormal toxicity test.
Among them: such as sterility inspection, pyrogen inspection, bacterial endotoxin, and abnormal toxicity inspection are indicators closely related to safety.
Polysaccharide content, free polysaccharide content, and efficacy test are indicators closely related to vaccine effectiveness.
Usually, a vaccine will go through a long research and development process of at least 8 years or even more than 20 years from research and development to marketing. The outbreak of the new crown epidemic requires no delay, and the design and development of vaccines is speeding up. It is not surprising in this special period. Of course, it is understandable that vaccine design, development and testing can be accelerated, shortened the cycle, and reduced some procedures. However, science needs to be rigorous and rigorous to achieve great results. The safety and effectiveness of vaccines are of the utmost importance. There must not be a single error. Otherwise, it will be counterproductive and need to be continuously improved and perfected.
Pre-clinical research: The screening of strains and cells is the basic guarantee to ensure the safety, effectiveness, and continuous supply of vaccines. Taking virus vaccines as an example, the laboratory stage needs to carry out strain screening, necessary strain attenuation, strain adaptation to the cultured cell matrix and stability studies in the process of passaging, and explore the stability of process quality, establish animal models, etc. . Choose mice, guinea pigs, rabbits or monkeys for animal experiments according to each vaccine situation. Pre-clinical research generally takes 5-10 years or longer on the premise that the process is controllable, the quality is stable, and it is safe and effective. In order to be safe and effective, a certain redundant design is also needed, so that the safety and effectiveness of the vaccine can be importantly guaranteed.
These include the establishment of vaccine strain/cell seed bank, production process research, quality research, stability research, animal safety evaluation and effectiveness evaluation, and clinical trial programs, etc.
The ARS-CoV-2 genome contains at least 10 ORFs. ORF1ab is converted into a polyprotein and processed into 16 non-structural proteins (NSP). These NSPs have a variety of functional biological activities, physical and chemical reactions, such as genome replication, induction of host mRNA cleavage, membrane rearrangement, autophagosome production, NSP polyprotein cleavage, capping, tailing, methylation, RNA double-stranded Uncoiling, etc., and others, play an important role in the virus life cycle. In addition, SARS-CoV-2 contains 4 structural proteins, namely spike (S), nucleocapsid (N), envelope (E) and membrane (M), all of which are encoded by the 3'end of the viral genome. Among the four structural proteins, S protein is a large multifunctional transmembrane protein that plays an important role in the process of virus adsorption, fusion, and injection into host cells, and requires in-depth observation and research.
1S protein is composed of S1 and S2 subunits, and each subunit can be further divided into different functional domains. The S1 subunit has 2 domains: NTD and RBD, and RBD contains conservative RBM. The S2 subunit has 3 structural domains: FP, HR1 and HR2. The S1 subunit is arranged at the top of the S2 subunit to form an immunodominant S protein.
The virus uses the host transmembrane protease Serine 2 (TMPRSS2) and the endosomal cysteine protease CatB/L to enter the cell. TMPRSS2 is responsible for the cleavage of the S protein to expose the FP region of the S2 subunit, which is responsible for initiating endosome-mediated host cell entry into it. It shows that TMPRSS2 is a host factor necessary for virus entry. Therefore, the use of drugs that inhibit this protease can achieve the purpose of treatment.
mRNA-1273
The mRNA encoding the full length of SARS-CoV-2, and the pre-spike protein fusion is encapsulated into lipid nanoparticles to form mRNA-1273 vaccine. It can induce a high level of S protein specific antiviral response. It can also consist of inactivated antigens or subunit antigens. The vaccine was quickly approved by the FDA and has entered phase II clinical trials. The company has announced the antibody data of 8 subjects who received different immunization doses. The 25ug dose group achieved an effect similar to the antibody level during the recovery period. The 100ug dose group exceeded the antibody level during the recovery period. In the 25ug and 100ug dose groups, the vaccine was basically safe and tolerable, while the 250ug dose group had 3 levels of systemic symptoms.
Viral vector vaccines can provide long-term high-level expression of antigen proteins, induce CTLs, and ultimately eliminate viral infections.
1, Ad5-nCov
A vaccine of SARS-CoV-2 recombinant spike protein expressed by recombinant, replication-deficient type 5 adenovirus (Ad5) vector. Load the optimized full-length S protein gene together with the plasminogen activation signal peptide gene into the E1 and E3 deleted Ad5 vectors. The vaccine is constructed by the Admax system derived from Microbix Biosystem. In phase I clinical trials, RBD (S1 subunit receptor binding domain) and S protein neutralizing antibody increased by 4 times 14 days after immunization, reaching a peak on 28 days. CD4+T and CD8+T cells reached a peak 14 days after immunization. The existing Ad5 immune resistance partially limits the response of antibodies and T cells. This study will be further conducted in the 18-60 age group, receiving 1/3 of the study dose, and follow-up for 3-6 months after immunization.
DNA vaccine
The introduction of antigen-encoding DNA and adjuvants as vaccines is the most innovative vaccine method. The transfected cells stably express the transgenic protein, similar to live viruses. The antigen will be endocytosed by immature DC, and finally provide antigen to CD4 + T, CD8 + T cells (by MHC differentiation) To induce humoral and cellular immunity. Some specificities of the virus and the new coronavirus mutant are different from general vaccines and other vaccines. Therefore, it is worth noting the gene expression of the vaccine. Otherwise, the effectiveness and efficiency of the vaccine will be questioned.
Live attenuated vaccine
DelNS1-SARS-CoV2-RBD
Basic influenza vaccine, delete NS1 gene. Express SARS-CoV-2 RBD domain. Cultured in CEF and MDCK (canine kidney cells) cells. It is more immunogenic than wild-type influenza virus and can be administered by nasal spray.
The viral genome is susceptible to mutation, antigen transfer and drift can occur, and spread among the population. Mutations can vary depending on the environmental conditions and population density of the geographic area. After screening and comparing 7,500 samples of infected patients, scientists found 198 mutations, indicating the evolutionary mutation of the virus in the human host. These mutations may form different virus subtypes, which means that even after vaccine immunization, viral infections may occur. A certain amount of increment and strengthening is needed here.
Inactivated vaccines, adenovirus vector vaccines, recombinant protein vaccines, nucleic acid vaccines, attenuated influenza virus vector vaccines, etc. According to relevant information, there are dozens of new coronavirus vaccines in the world, and more varieties are being developed and upgraded. Including the United States, Britain, China, Russia, India and other countries, there are more R&D and production units.
AZ vaccine
Modena vaccine
Lianya Vaccine
High-end vaccine
Pfizer vaccine
Pfizer-BioNTech
A large study found that the vaccine developed by Pfizer and German biotechnology company BioNTech is 95% effective in preventing COVID-19.
The vaccine is divided into two doses, which are injected every three weeks.
This vaccine uses a molecule called mRNA as its basis. mRNA is a molecular cousin of DNA, which contains instructions to build specific proteins; in this case, the mRNA in the vaccine encodes the coronavirus spike protein, which is attached to the surface of the virus and used to infect human cells. Once the vaccine enters the human body, it will instruct the body's cells to make this protein, and the immune system will learn to recognize and attack it.
Moderna
The vaccine developed by the American biotechnology company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) is also based on mRNA and is estimated to be 94.5% effective in preventing COVID-19.
Like Pfizer's vaccine, this vaccine is divided into two doses, but injected every four weeks instead of three weeks. Another difference is that the Moderna vaccine can be stored at minus 20 degrees Celsius instead of deep freezing like Pfizer vaccine. At present, the importance of one of the widely used vaccines is self-evident.
Oxford-AstraZeneca
The vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca is approximately 70% effective in preventing COVID-19-that is, in clinical trials, adjusting the dose seems to improve this effect.
In the population who received two high-dose vaccines (28 days apart), the effectiveness of the vaccine was about 62%; according to early analysis, the effectiveness of the vaccine in those patients who received the half-dose first and then the full-dose Is 90%. However, in clinical trials, participants taking half doses of the drug are wrong, and some scientists question whether these early results are representative.
Sinopharm Group (Beijing Institute of Biological Products, China)
China National Pharmaceutical Group Sinopharm and Beijing Institute of Biological Products have developed a vaccine from inactivated coronavirus (SARS-CoV-2). The inactivated coronavirus is an improved version that cannot be replicated.
Estimates of the effectiveness of vaccines against COVID-19 vary.
Gamaleya Institute
The Gamaleya Institute of the Russian Ministry of Health has developed a coronavirus vaccine candidate called Sputnik V. This vaccine contains two common cold viruses, adenoviruses, which have been modified so that they will not replicate in the human body; the modified virus also contains a gene encoding the coronavirus spike protein.
New crown drugs
There are many small molecule antiviral drug candidates in the clinical research stage around the world. Including traditional drugs in the past and various drugs yet to be developed, antiviral drugs, immune drugs, Gene drugs, compound drugs, etc.
(A) Molnupiravir
Molnupiravir is a prodrug of the nucleoside analog N4-hydroxycytidine (NHC), jointly developed by Merck and Ridgeback Biotherapeutics.
The positive rate of infectious virus isolation and culture in nasopharyngeal swabs was 0% (0/47), while that of patients in the placebo group was 24% (6/25). However, data from the Phase II/III study indicate that the drug has no benefit in preventing death or shortening the length of stay in hospitalized patients.
Therefore, Merck has decided to fully advance the research of 800mg molnupiravir in the treatment of patients with mild to moderate COVID-19.
(B) AT-527
AT-527 is a small molecule inhibitor of viral RNA polymerase, jointly developed by Roche and Atea. Not only can it be used as an oral therapy to treat hospitalized COVID-19 patients, but it also has the potential as a preventive treatment after exposure.
Including 70 high-risk COVID-19 hospitalized patients data, of which 62 patients' data can be used for virological analysis and evaluation. The results of interim virological analysis show that AT-527 can quickly reduce viral load. On day 2, compared with placebo, patients treated with AT-527 had a greater decline in viral load than the baseline level, and the continuous difference in viral load decline was maintained until day 8.
In addition, compared with the control group, the potent antiviral activity of AT-527 was also observed in patients with a baseline median viral load higher than 5.26 log10. When testing by RT-qPCR to assess whether the virus is cleared,
The safety aspect is consistent with previous studies. AT-527 showed good safety and tolerability, and no new safety problems or risks were found. Of course, there is still a considerable distance between experiment and clinical application, and a large amount of experimental data can prove it.
(C) Prokrutamide
Prokalamide is an AR (androgen receptor) antagonist. Activated androgen receptor AR can induce the expression of transmembrane serine protease (TMPRSS2). TMPRSS2 has a shearing effect on the new coronavirus S protein and ACE2, which can promote the binding of viral spike protein (S protein) to ACE, thereby promoting The virus enters the host cell. Therefore, inhibiting the androgen receptor may inhibit the viral infection process, and AR antagonists are expected to become anti-coronavirus drugs.
Positive results were obtained in a randomized, double-blind, placebo-controlled phase III clinical trial. The data shows that Prokalutamide reduces the risk of death in severely ill patients with new coronary disease by 92%, reduces the risk of new ventilator use by 92%, and shortens the length of hospital stay by 9 days. This shows that procrulamide has a certain therapeutic effect for patients with severe new coronary disease, which can significantly reduce the mortality of patients, and at the same time greatly reduce the new mechanical ventilation and shorten the patient's hospital stay.
With the continuous development of COVID-19 on a global scale, in addition to vaccines and prevention and control measures, we need a multi-pronged plan to control this disease. Oral antiviral therapy undoubtedly provides a convenient treatment option.
In addition, there are other drugs under development and experimentation. In dealing with the plague virus, in addition to the strict control of protective measures, it is very important that various efficient and safe vaccines and various drugs (including medical instruments, etc.) are the ultimate nemesis and killer of the virus.
(A) "Antiviral biological missiles" are mainly drugs for new coronaviruses and mutant viruses, which act on respiratory and lung diseases. The drugs use redundant designs to inhibit new coronaviruses and variant viruses.
(B) "New Coronavirus Epidemic Prevention Tablets" mainly use natural purified elements and chemical structure modifications.
(C) "Composite antiviral oral liquid" antiviral intermediate, natural antiviral plant, plus other preparations
(D) "New Coronavirus Long-acting Oral Tablets" Chemical modification of antiviral drugs, multiple targets, etc.
(E) "New Coronavirus Inhibitors" (injections) are mainly made of chemical drug structure modification and other preparations.
The development of these drugs mainly includes: drug target screening, structure-activity relationship, chemical modification, natural purification, etc., which require a lot of work and experimentation.
Humans need to vigorously develop drugs to deal with various viruses. These drugs are very important for the prevention and treatment of viruses and respiratory infectious diseases, influenza, pneumonia, etc.
The history of human development The history of human evolution, like all living species, will always be accompanied by the survival and development of microorganisms. It is not surprising that viruses and infectious diseases are frequent and prone to occur. The key is to prevent and control them before they happen.
This strain was first discovered in India in October 2020 and was initially called a "double mutant" virus by the media. According to the announcement by the Ministry of Health of India at the end of March this year, the "India New Coronavirus Genomics Alliance" composed of 10 laboratories found in samples collected in Maharashtra that this new mutant strain carries E484Q and L452R mutations. , May lead to immune escape and increased infectivity. This mutant strain was named B.1.617 by the WHO and was named with the Greek letter δ (delta) on May 31.
Shahid Jamil, the dean of the Trivedi School of Biological Sciences at Ashoka University in India and a virologist, said in an interview with the Shillong Times of India that this mutant strain called "double mutation" is not accurate enough. B. 1.617 contains a total of 15 mutations, of which 6 occur on the spike protein, of which 3 are more critical: L452R and E484Q mutations occur on the spike protein and the human cell "Angiotensin Converting Enzyme 2 (ACE2)" receptor In the bound region, L452R improves the ability of the virus to invade cells, and E484Q helps to enhance the immune escape of the virus; the third mutation P681R can also make the virus enter the cell more effectively. (Encyclopedia website)
There are currently dozens of antiviral COVID-19 therapies under development. The large drugmakers Merck and Pfizer are the closest to the end, as expected, a pair of oral antiviral COVID-19 therapies are undergoing advanced human clinical trials.
Merck's drug candidate is called monupiravir. It was originally developed as an influenza antiviral drug several years ago. However, preclinical studies have shown that it has a good effect on SARS and MERS coronavirus.
Monupiravir is currently undergoing in-depth large-scale Phase 3 human trials. So far, the data is so promising that the US government recently pre-ordered 1.7 million courses of drugs at a cost of $1.2 billion. If everything goes according to plan, the company hopes that the drug will be authorized by the FDA for emergency use and be on the market before the end of 2021.
Pfizer's large COVID-19 antiviral drug candidate is more unique. Currently known as PF-07321332, this drug is the first oral antiviral drug to enter human clinical trials, specifically targeting SARS-CoV-2.
Variant of Concern WHO Label First Detected in World First Detected in Washington State
B.1.1.7 Alpha United Kingdom, September 2020 January 2021
B.1.351 Beta South Africa, December 2020 February 2021
P.1 Gamma Brazil, April 2020 March 2021
B.1.617.2 Delta India, October 2020 April 2021
Although this particular molecule was developed in 2020 after the emergence of the new coronavirus, a somewhat related drug called PF-00835231 has been in operation for several years, targeting the original SARS virus. However, the new drug candidate PF-07321332 is designed as a simple pill that can be taken under non-hospital conditions in the initial stages of SARS-CoV-2 infection.
"The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in the cell," Pfizer said when explaining the mechanism of its new antiviral drug. "Protease inhibitors have been effective in the treatment of other viral pathogens, such as HIV and hepatitis C virus, whether used alone or in combination with other antiviral drugs. Currently marketed therapeutic drugs for viral proteases are generally not toxic Therefore, such molecules may provide well-tolerated treatments against COVID-19."
Various studies on other types of antiviral drugs are also gaining momentum. For example, the new coronavirus pneumonia "antiviral biological missile", "new coronavirus prevention tablets", "composite antiviral oral liquid", "new coronavirus long-acting oral tablets", "new coronavirus inhibitors" (injections), etc., are worthy of attention. Like all kinds of vaccines, they will play a major role in preventing and fighting epidemics.
In addition, Japanese pharmaceutical company Shionoyoshi Pharmaceutical is currently conducting a phase 1 trial of a protease inhibitor similar to SARS-CoV-2. This is called S-217622, which is another oral antiviral drug, and hopes to provide people with an easy-to-take pill in the early stages of COVID-19. At present, the research and development of vaccines and various new crown drugs is very active and urgent. Time does not wait. With the passage of time, various new crown drugs will appear on the stage one after another, bringing the gospel to the complete victory of mankind.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-CoV-2 strain in the world. Although our vaccine is still maintained, it is clear that we need more tools to combat this new type of coronavirus. Delta will certainly not be the last new SARS-CoV-2 variant we encountered. Therefore, it is necessary for all mankind to persevere and fight the epidemic together.
Overcome illness and meet new challenges. The new crown epidemic and various mutated viruses are very important global epidemic prevention and anti-epidemic top priorities, especially for the current period of time. Vaccine injections, research and development of new drugs, strict prevention and control, wear masks, reduce gatherings, strictly control large gatherings, prevent the spread of various viruses Masks, disinfection and sterilization, lockdown of the city, vaccinations, accounting and testing are very important, but this does not mean that humans can completely overcome the virus. In fact, many spreading and new latently transmitted infections are still unsuccessful. There are detections, such as invisible patients, asymptomatic patients, migratory latent patients, new-onset patients, etc. The struggle between humans and the virus is still very difficult and complicated, and long-term efforts and exploration are still needed, especially for medical research on the new coronavirus. The origin of the disease, the course of the disease, the virus invaded The deep-level path and the reasons for the evolution and mutation of the new coronavirus and the particularity of prevention and treatment, etc.). Therefore, human beings should be highly vigilant and must not be taken lightly. The fierce battle between humans and various viruses must not be slackened. Greater efforts are needed to successfully overcome this pandemic, fully restore the normal life of the whole society, restore the normal production and work order, restore the normal operation of society, economy and culture, and give up food due to choking. Or eager for success, will pay a high price.
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References References are made to web resources, and related images are from web resources and related websites.
Who official website UN .org www.gavi.org/ispe.org
Wikipedia, "The Lancet", "English Journal of Medicine", "Nature", "Science", "Journal of the American Medical Association", etc.
Learning from history: do not flatten the curve of antiviral research!
T Bobrowski, CC Melo-Filho, D Korn, VM Alves...-Drug discovery today, 2020-
A critical overview of computational approaches employed for COVID-19 drug discovery
EN Muratov, R Amaro, CH Andrade, N Brown...-Chemical Society..., 2021-pubs.rsc.org
Global Research Performance on COVID 19 in Dimensions Database
J Balasubramani, M Anbalagan-2021-researchgate.net
Adoption of a contact tracing app for containing COVID-19: a health belief model approach
M Walrave, C Waeterloos...- JMIR public health and..., 2020-publichealth.jmir.org
Prophylactic Treatment Protocol Against the Severity of COVID-19 Using Melatonin
N Charaa, M Chahed, H Ghedira...-Available at SSRN..., 2020-papers.ssrn.com
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, The Lancet
Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany, New England Journal of Medicine
The actions of respiratory therapists facing COVID-19
Zhu Jiacheng-Respiratory Therapy, 2021-pesquisa.bvsalud.org
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, The Lancet
Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China, JAMA, February 7
Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China, JAMA
Delta variant triggers new phase in the pandemic | Science
science.sciencemag.org›
COVID vaccines slash viral spread – but Delta is an unknown
www.nature.com ›articles
Novel coronavirus pneumonia during ophthalmic surgery management strategy and recommendations
YH HUANG, SS LI, X YAO, YR YANG, DH QIN…-jnewmed.com
Delta variant: What is happening with transmission, hospital ...
Risk of long QT syndrome in novel coronavirus COVID-19
VN Oslopov, JV Oslopova, EV Hazova…-Kazan medical…, 2020-kazanmedjournal.ru
Study compares mRNA and adenovirus-based SARS-CoV-2 vaccines ...
First molecular-based detection of SARS-CoV-2 virus in the field-collected houseflies
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Covid 19 DELTA Variant Archives-Online essay writing service
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SARS-CoV-2 Delta variant Likely to become dominant in the ...
Compilation postscript
Once Fang Ruida's research literature on the new crown virus and mutant virus was published, it has been enthusiastically praised by readers and netizens in dozens of countries around the world, and has proposed some amendments and suggestions. Hope to publish a multilingual version of the book as an emergency To meet the needs of many readers around the world, in the face of the new crown epidemic and the prevention and treatment of various mutant viruses, including the general public, college and middle school students, medical workers, medical colleagues and so on. According to the English original manuscript, it will be re-compiled and published. Inconsistencies will be revised separately. Thank you very much.
Jacques Lucy, Geneva, Switzerland, August 2021
*********************************************************************
Leader mondial, scientifique, scientifique médical, virologue, pharmacien et professeur Fangruida (F.D Smith) sur l'épidémie mondiale et l'ennemi juré et la prévention des nouveaux coronavirus et virus mutants (Jacques Lucy 2021v1.5)
_-----------------------------------------
L'ennemi juré et le tueur du nouveau coronavirus et des virus mutés - Développement conjoint de vaccins et de médicaments (Fangruida) Juillet 2021
* La particularité des nouveaux coronavirus et des virus mutants * Le large spectre, la haute efficacité, la redondance et la sécurité de la conception et du développement du nouveau vaccin contre le coronavirus, Redondance et sécurité
I. Targeting Iran’s Nuclear and Missile Proliferation Activities
One set of today’s actions targets Iran’s nuclear and missile proliferation activities by designating entities and individuals that are part of the international procurement and nuclear proliferation operations of Iran’s Ministry of Defense for Armed Forces Logistics (MODAFL); Aerospace Industries Organization (AIO); Iran’s national maritime carrier, Islamic Republic of Iran Shipping Lines (IRISL); and Iran’s Islamic Revolutionary Guard Corps (IRGC) – all of which have been previously designated under Executive Order (E.O.) 13382, “Blocking Property of Weapons of Mass Destruction Proliferators and Their Supporters.” Treasury today is also updating the identifying information for 57 vessels affiliated with IRISL that had been renamed or reflagged since they were originally designated by Treasury, and identifying seven vessels affiliated with IRISL that have not been identified previously. U.S. persons are generally prohibited from engaging in any transactions with individuals or entities designated pursuant to E.O 13382, and any assets the designees may have under U.S. jurisdiction are blocked.
Designations Related to MODAFL and AIO
Iran’s Ministry of Defense for Armed Forces Logistics (MODAFL) oversees Iran’s ballistic missile program. It is designated by the United States pursuant to E.O. 13382 in 2007, and has brokered a number of transactions involving materials and technologies with ballistic missile applications. Aerospace Industries Organization (AIO), a subsidiary of MODAFL, oversees all of Iran’s missile industries and was listed in the Annex to E.O. 13382. Today’s MODAFL- and AIO-related designations under E.O. 13382 include:
Electronic Components Industries Co. (ECI) and Information Systems Iran (ISIRAN)
Electronic Components Industries Co. (ECI) and Information Systems Iran (ISIRAN) are being designated pursuant to E.O. 13382 because they are owned or controlled by Iran Electronics Industries (IEI), which was designated pursuant to E.O. 13382 in 2008 for being owned or controlled by MODAFL. IEI offers a diversified range of military products including electro-optics and lasers, communication equipment, telecommunication security equipment, electronic warfare equipment, new and refurbished radar tubes, and missile launchers. IEI manufactures military tactical communication systems and also electronic field telephones and switchboards.
ECI conducts work on military and civilian projects, to include semi-conductors, multilayer single and double sided printed circuit boards, hybrid circuits, quartz crystals and oscillators, high purity oxygen and nitrogen gases, micromodules and electronic ceramics.
ISIRAN is one of the largest and most experienced information technology companies in Iran with expertise in building mainframes, minicomputers and PC hardware, software and maintenance as well as total solution turn-key projects.
Advanced Information and Communication Technology Center
Advanced Information and Communication Technology Center (AICTC) is being designated pursuant to E.O. 13382 because it has provided technological or other support for, or services in support of ISIRAN. According to information available from computers abandoned by Hamid Reza Rabiee in the United States, AICTC executes work projects on behalf of ISIRAN. AICTC has five research groups in the fields of Enterprise Software Solutions, Multimedia Systems, Mobile Value-Added Services, Wireless and P2P Networks and Bioinformatics. It also does work on GIS/GPS based tracking systems and more.
Hamid Reza Rabiee
Hamid Reza Rabiee, a software engineer, is being designated pursuant to E.O. 13382 for acting or purporting to act for or on behalf of AICTC. According to information available from computers abandoned by Rabiee in the United States, he has coordinated directly with ISIRAN to establish and execute contracts benefitting ISIRAN. Rabiee is the chief architect and founder of AICTC, and is the current director of the organization.
Digital Media Lab (DML) and Value-Added Services Laboratory (VASL)
Digital Media Lab (DML) and Value-Added Services Laboratory (VASL) were designated for being owned or controlled by, or acting or purporting to act for or on behalf of Hamid Reza Rabiee and AICTC. According to publicly available information, Rabiee is the founder and director of DML and VASL.
Ministry of Defense Logistics Export (MODLEX)
MODLEX is being designated pursuant to E.O. 13382 because it is owned or controlled by, or acts or purports to act, for or on behalf of, MODAFL. As MODAFL’s primary exporting entity since 2009, MODLEX was involved in the trade of exportable military products to countries including Sri Lanka, Sudan, Burma, Bangladesh and Nigeria, all in contravention of UNSCR 1747 (2007). UNSCR 1747 prohibits Iran from selling any arms or related material. MODLEX represents Iran at arms trade fairs worldwide advertising Iranian military products for sale. MODLEX also conducts limited procurement activities on behalf of MODAFL elements such as Iran’s Defense Industries Organization (DIO), AIO, and Shahid Bakeri Industrial Group (SBIG). Both DIO and SBIG are sanctioned under UNSCR 1737 for their links to Iran’s missile program through MODAFL and AIO, respectively.
The Annex to UNSCR 1929 (2010) lists MODLEX as an entity involved in Iran’s nuclear or ballistic missile activities and identified MODLEX as being owned or controlled by MODAFL.
Daniel Frosch and International General Resourcing FZE
Daniel Frosch is being designated pursuant to E.O. 13382 for providing or attempting to provide material support for AIO.
Daniel Frosch for several years has shown a steady pattern of providing support to Iran’s missile program, including Shahid Hemmat Industrial Group (SHIG) and SBIG, by supplying it with sensitive material. He started dealing with Iran’s missile industry while in his home country of Austria, under his now defunct company Daniel Frosch Exports. He moved to the United Arab Emirates(UAE) in 2006, where he continued supporting Iran’s weapons programs. Frosch has supplied Iran’s missile industry with a wide range of goods, including electronics, testing equipment, and raw materials such as graphite with potential applications in Iran’s ballistic missile program. Frosch is the owner of International General Resourcing FZE, located in the UAE.
SHIG was identified in the Annex to E.O. 13382 and is tied to Iran’s ballistic missile research, development, and production activities. SHIG was also listed in the Annex to UNSCR 1737.
Malek Ashtar University
Malek Ashtar University is being designated pursuant to E.O. 13382 for being owned or controlled by MODAFL. Malek Ashtar University was established in 1986 by Iran’s Ministry of Higher Education and the Supreme Council of the Cultural Revolution, and it is one of the major research institutes and educational centers contained under the MODAFL umbrella.
Malek Ashtar University was identified in the Annex to UNSCR 1929 because it is a subordinate of the Defense Technology and Science Research Center (DTSRC) within MODAFL. The European Union designated Malek Ashtar University on June 24, 2008, because Malek Ashtar University is linked to MODAFL. The University also created a missile training program in 2003 in close collaboration with AIO.
Actions Related to Islamic Republic of Iran Shipping Line (IRISL)
IRISL, Iran’s national maritime carrier, was designated by Treasury pursuant to E.O. 13382 in September 2008 for its provision of logistical services to MODAFL.
Good Luck Shipping
Good Luck Shipping (GLS), which is located in the UAE, is being designated pursuant to E.O. 13382 because it acts or purports to act for or on behalf of IRISL. GLS was established to replace Great Ocean Shipping Services, which was designated pursuant to E.O. 13382 in June 2011.
Great Ocean Shipping Services (Great Ocean), along with Oasis Freight Agency LLC (Oasis) and Pearl Ship Management LLC (Pearl), are being removed from the SDN List because they were liquidated and struck from the Dubai, UAE commercial register. Great Ocean was designated in June 2011 for acting for or on behalf of IRISL affiliate Oasis and/or IRISL. Oasis was designated pursuant to E.O. 13382 in September 2008 for being owned or controlled by, or acting or purporting to act for or on behalf of, directly or indirectly, IRISL. Pearl was also designated in June 2011 for acting for or on behalf of Oasis and/or IRISL.
Identification of Renamed, Reflagged Vessels and Additional IRISL Vessels
Today, Treasury updated its List of Specially Designated Nationals and Blocked Persons (SDN List) entries for 57 vessels affiliated with IRISL that, since their original identification, have been renamed and/or reflagged by IRISL and its affiliates. OFAC is also identifying 7 additional vessels as blocked property in which IRISL has an interest. Including today’s additions, Treasury has identified 155 ships as blocked property in which IRISL or designated IRISL affiliates have an interest.
Designation of IRGC Officer
The IRGC was designated pursuant to E.O. 13382 in 2007 for having engaged, or attempting to engage, in proliferation-related activities. The IRGC continues to be a primary focus of U.S. and international sanctions against Iran because of the central role it plays in Iran’s ballistic missile and nuclear programs and its involvement in serious human rights abuses.
Ali Fadavi
Islamic Revolutionary Guard Corps (IRGC) Navy Commander Ali Fadavi is being designated under E.O. 13382 for acting or purporting to act for or on behalf of, directly or indirectly, the IRGC. Fadavi was appointed by the Supreme Leader Khamenei as the new IRGC Navy Commander on May 3, 2010. On September 21, 2010, the Defense Ministry of Iran announced that it had delivered the third generation of the domestically designed and manufactured Fateh-110 high-precision ballistic missiles to the IRGC. Fadavi was present at the ceremony where the missiles were delivered. In November 2010 under Fadavi’s leadership, the IRGCNavy organized and trained around 60,000 Basij students who received instruction in techniques aimed to confront enemies of Iran. Fadavi claimed that around 100,000 students had become members of the Shahid Fahmideh Rahrovan camp of Basij forces in Bandar Abbas after the launch of the education project.
The European Union designated Fadavi on July 26, 2010, pursuant to European Union Council authorities, for his role as an IRGC Navy Commander.
Designation of Nuclear Procurement Entities
Pentane Chemistry Industries
Pentane Chemistry Industries (PCI) is being designated for engaging or attempting to engage in activities that have materially contributed to, or posed a risk of contributing to, the development of Iran’s Weapons of Mass Destruction (WMD) programs.
PCI is an Iranian entity involved in building distillation columns for the production of heavy water for use in Iran’s IR-40 heavy water reactor, under construction in Arak, Iran. Since late 2009 PCI has been in charge of the distillation column project at this reactor. PCI has also attempted to procure phosphor bronze mesh as recently as July 2011. Phosphor bronze mesh can be used in distillation columns for final enrichment of heavy water. PCI began manufacturing phosphor bronze mesh screens for the distillation columns in March 2012. Chemically-treated phosphor bronze, when knitted into mesh screens, will be used as packing in the IR-40 distillation columns.
Hossein Tanideh
Hossein Tanideh was a procurement agent for Iran’s nuclear program through late 2011. He was the Vice President of Iran’s Pentane Chemistry Industries Board of Directors as well as Managing Director of the Sherkate Sakhtemani Rahtes Sahami Company (also known as the Rahtes Company). Tanideh in 2010 and 2011 attempted to procure items for probable use in distillation columns for Iran’s 40-megawatt heavy water research reactor.
Center for Innovation and Technology Cooperation
The Center for Innovation and Technology Cooperation (CITC) is in a position to support a range of Iran’s weapons of mass destruction (WMD) and military procurement objectives. It has been assessed that CITC facilitates procurement and technology transfer from the science community to the military services.
II. Preventing the Circumvention of International Sanctions
To prevent the circumvention of international sanctions on Iran, including sanctions on oil trade with Iran, Treasury is publicly exposing numerous entities that are part of the Government of Iran. Treasury is identifying these Government of Iran entities pursuant to E.O. 13599, which blocks all property and interests in property within U.S. jurisdiction of the Government of Iran and of Iranian financial institutions, and prohibits U.S. persons or those within U.S. jurisdiction from having dealings with them. These identifications are being issued to assist U.S. persons in complying with E.O. 13599, but are not required for E.O. 13599 to apply. Every entity that meets the definition of Government of Iran or an Iranian financial institution under E.O. 13599 is blocked, regardless of whether it has been identified and added to the SDN List. Today’s actions include:
Exposing front companies involved in Iran’s oil trade
Aiming to undercut Iran’s attempts to obscure Iran’s petroleum trade in the face of increasing international sanctions, Treasury is identifying Petro Suisse Intertrade Company SA (Petro Suisse), an entity incorporated in Switzerland; Hong Kong Intertrade Company, a Hong Kong-based entity; Noor Energy (Malaysia) Ltd, an entity incorporated in Malaysia; and Petro Energy Intertrade Company, an entity operating out of Dubai, as blocked pursuant to E.O. 13599 because they are owned or controlled by, or acting for or on behalf of, the Government of Iran. Each of these entities are front companies for the National Iranian Oil Company (NIOC), Naftiran Intertrade Company Ltd. (NICO), or Naftiran Intertrade Co. (NICO) Sarl (NICO Sarl).
Prior to the issuance of E.O. 13599, Iran’s NIOC, NICO, and NICO Sarl, a Swiss subsidiary of NICO, were identified in 2008, by OFAC as entities that are owned or controlled by the Government of Iran within the meaning of the Iranian Transactions Regulations. U.S. persons are generally prohibited from engaging in any transactions with NIOC, NICO, and NICO Sarl, without authorization from OFAC.
Identification of additional Iranian financial institutions
The 20 Iranian financial institutions identified in today’s action constitute new additions to the SDN List that were blocked pursuant to E.O. 13599 on February 5, 2012. Three of the entities identified today have previously been designated by Treasury’s Office of Foreign Assets Control (OFAC) under other authorities, and their entries on the SDN List have been updated to reflect their status as Iranian financial institutions.
These identifications, which include the publication of the names and aliases of the Iranian financial institutions, are intended to aid the public in meeting its obligations under E.O. 13599.
To receive a list of these 20 Iranian financial institutions please contact Treasury Public Affairs
Identification of NITC Vessels
Treasury is identifying 58 National Iranian Tanker Company (NITC) vessels, as well as NITC and 27 of its affiliated entities, as blocked or “frozen” pursuant to E.O. 13599. The NITC entities have been identified as Government of Iran entities, and the NITC vessels have been identified as property of the Government of Iran. These identifications will aid companies and individuals in complying with sanctions against the Government of Iran and undermine Iran’s attempts to use NITC front companies or renamed vessels to evade sanctions.
****
Fact Sheet
Office of the Spokesperson
Washington, DC
July 12, 2012
bit.ly/upvOoIBiology is a very wide field of study with numerous specialized areas like marine biology, environmental studies, biochemistry, microbiology, and many others. Generally speaking, biologists study living organisms. While there are entry-level jobs available for those with only a bachelor's degree in Biology, usually a master's degree or doctorate, or some type of specialized training is needed in order to qualify for most positions in the biological sciences. Here are some of the most common career possibilities for students who have at least a bachelor's degree in Biology. Researchers with a biology degree dedicate themselves to understanding how living systems work. Their goals are to increase our scientific knowledge and find practical solutions to biological problems that may involve animals, plants, the environment, health care, agriculture, and many other topics in the biological sciences. While many research biologists work in laboratories, some also do fieldwork to gather data and conduct their studies. Biologists who specialize in health care can work to control the spread of diseases by developing or administering vaccines and treatments. These biologists may also be involved in organizing public health campaigns to help people understand how to protect themselves against illness and what to do if they get sick. Environmental management and conservation biologists are dedicated to preserving nature and resolving environmental issues. These biologists often work with the public and special interest groups (like landowners, local governments, and businesses) to develop and implement effective plans and programs to preserve the natural world. Types of environmental management biologists include park rangers, who protect state and national parks, and zoo biologists who organize endangered species recovery programs. Biology educators work in classrooms, research labs, museums, or out in the field to teach others more about the biological sciences. Depending on their interests and qualifications, these biologists may teach at every academic level from elementary school through postgraduate studies. And biological educators may teach, lead tours and nature hikes, and design exhibits and educational programs for science museums, zoos, aquariums, parks, and nature centers. Biotechnology biologists focus on the use of living organisms and bioprocesses to develop and improve products and tools in the areas of health care (medical), crop production (agricultural), non food uses of crops and other natural products such as biodegradable plastics and biofuels (industrial), and environmental concerns. The concept of biotechnology includes a wide range of procedures to modify living organisms to better serve human needs, including selective breeding, hybridization, and now even cloning. Forensic biologists often work in a laboratory, studying evidence, writing reports and testifying in court as expert witnesses. While forensic scientists may also visit crime or other incident scenes to help reconstruct the crime or collect or preserve evidence, usually this work is done by specially trained crime scene examiners. Forensic scientists usually work for government agencies, forensic laboratories, police departments, hospitals, and universities. Graduates with a biology degree can also serve as science advisors who work with lawmakers to create new legislation on biological issues such as biomedical research, environmental protection, and genetically-modified organisms. Their specialized knowledge can help educate lawmakers and the general public and help ensure that policy decisions are made which are backed by proven scientific evidence and research. Business and industry biologists work with pharmaceutical companies and scientific supply companies to research and test new products. They may also use their specialized biological knowledge in sales, marketing, and public relations positions to help educate their fellow biologists and the general public about new products that are being developed. Economic biologists work with larger entities like governments, businesses, and Native American tribes to study and address the economic impacts of widespread biological issues including species extinctions, acid rain, renewable forests, brownfields, and environmental pollution. Mathematical biologists work in fields like bioinformatics and computational biology where they can apply mathematical techniques like modeling ecosystem processes and gene sequencing to solve biological problems. Biological journalists and writers with a science background and a biology degree use their communications skills to keep the general public informed about important biological issues on a wide range of medical, environmental, industrial and agricultural topics. These biologists form an important link that translates specialized, highly technical scientific research into concepts that non-scientists can easily understand. Finally, biological artists use their biological knowledge to provide accurate and detailed illustrations and drawings for science textbooks, as well as newspaper, magazine and online science articles.
www.ebi.ac.uk/training/schools/decode/ (unfortunately this EBI link is now dead)
or
www.ebi.ac.uk/cgi-bin/decode/decode.cgi
Duncan's personalised decode results
name = *DXNCAN*
Why has decode put some 'X's in my name?
There are only 20 amino acids encoded by DNA, so there might be some
letters in your name that do not stand for any amino acids (O or Z, for
example). Decode replaces these letters with an X, which means 'any
amino acid'.
Duncan's name in DNA:
GACNNNAACTGCGCCAAC
This DNA sequence is similar to the protein called Q9VDN2|MT3_DROME.
This protein is found in the species Drosophila melanogaster, more commonly known as Fruit fly.
>Q9VDN2|MT3_DROME Metallothionein-3 (MT-3) (Metallothionein C) - Drosophila melanogaster (Fruit fly)
sequence:
MVCKGCGTNCKCQDTKCGDNCACNQDCKCVCKNGPKDQCCKSK
The HASP Server was designed as a scientific tool for researchers to visualize their phylogenetic, biochemical, and immunological hemagglutinin (HA) data in the three-dimensional context of the HA structure, in the hopes that the context may help researchers better interpret their data and generate new hypotheses. Credit: NIAID
www.niaid.nih.gov/LabsAndResources/resources/bioinformati...
Mingle Media TV and Red Carpet Report host Paige Sullivan were invited to come back and cover the 2nd Annual Rebels with a Cause Gala at Paramount Studios honoring Larry Ellison with Jimmy Kimmel hosting and special guest performances by Barry Manilow and Pharrell Williams. This event supports the lifesaving research of David B. Agus, M.D. at USC’s Center for Applied Molecular Medicine.
Get the Story from the Red Carpet Report Team, follow us on Twitter and Facebook at:
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www.youtube.com/MingleMediaTVNetwork
ABOUT THE USC CENTER FOR APPLIED MOLECULAR MEDICINE
The principal goal of the USC Center for Applied Molecular Medicine is the development of novel treatment strategies for cancer. The Center was implemented to enable a convergence of multiple disciplines to work on treatment and the care of patients with cancer. The program includes the clinical care of patients with cancer at the USC Westside Cancer Center in Beverly Hills and has team members with expertise spanning cancer biology, biochemistry, molecular biology, bioinformatics, computer science, electrical engineering, bioorganic chemistry, physics and applied mathematics. For information, visit camm.usc.edu/.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
www.facebook.com/minglemediatvnetwork
www.flickr.com/MingleMediaTVNetwork
Follow our host Paige Sullivan on Twitter at twitter.com/PaigeSull
From: www.connectedaction.net
Connections among the Twitter users who recently tweeted the words bioinformatics
when queried on April 27, 2011, scaled by numbers of followers (with outliers thresholded).
Layout using the "Group Layout" composed of tiled bounded regions. Clusters calculated by the Clauset-Newman-Moore algorithm are also encoded by color.
A larger version of the network map is here: www.flickr.com/photos/marc_smith/5663118647/sizes/o/
A detailed list of top most between users is here: www.flickr.com/photos/marc_smith/5663118545/
Top most between users:
@bioinfo
@kshameer
@biomol_info
@genegeek
@32nm
@yokofakun
@marina_manrique
@pathogenomenick
@hannahjwaters
@kristiholmes
Graph Metric: Value
Graph Type: Directed
Vertices: 258
Unique Edges: 419
Edges With Duplicates: 50
Total Edges: 469
Self-Loops: 0
Connected Components: 174
Single-Vertex Connected Components: 163
Maximum Vertices in a Connected Component: 74
Maximum Edges in a Connected Component: 450
Maximum Geodesic Distance (Diameter): 6
Average Geodesic Distance: 2.465133
Graph Density: 0.006696227
NodeXL Version: 1.0.1.166
NodeXL is free and open and available from www.codeplex.com/nodexl
NodeXL is developed by the Social Media Research Foundation (www.smrfoundation.org) - which is dedicated to open tools, open data, and open scholarship.
The book, Analyzing social media networks with NodeXL: Insights from a connected world, is available from Morgan Kaufmann and from Amazon.
Marc Smith on Twitter.
Mingle Media TV and Red Carpet Report host Paige Sullivan were invited to come back and cover the 2nd Annual Rebels with a Cause Gala at Paramount Studios honoring Larry Ellison with Jimmy Kimmel hosting and special guest performances by Barry Manilow and Pharrell Williams. This event supports the lifesaving research of David B. Agus, M.D. at USC’s Center for Applied Molecular Medicine.
Get the Story from the Red Carpet Report Team, follow us on Twitter and Facebook at:
www.facebook.com/RedCarpetReportTV
www.youtube.com/MingleMediaTVNetwork
ABOUT THE USC CENTER FOR APPLIED MOLECULAR MEDICINE
The principal goal of the USC Center for Applied Molecular Medicine is the development of novel treatment strategies for cancer. The Center was implemented to enable a convergence of multiple disciplines to work on treatment and the care of patients with cancer. The program includes the clinical care of patients with cancer at the USC Westside Cancer Center in Beverly Hills and has team members with expertise spanning cancer biology, biochemistry, molecular biology, bioinformatics, computer science, electrical engineering, bioorganic chemistry, physics and applied mathematics. For information, visit camm.usc.edu/.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
www.facebook.com/minglemediatvnetwork
www.flickr.com/MingleMediaTVNetwork
Follow our host Paige Sullivan on Twitter at twitter.com/PaigeSull
www.sk.ru/en Boston, USA 18JUN2012
Representatives from the Skolkovo Foundation participated in the 2012 BIO International Convention at the Boston Convention and Exhibition Center June 18-21. The conference, attended by pharmaceutical companies, teaching hospitals, venture capital firms and over 500 biotechnology companies, drew more than 15,000 attendees to the Boston area.
Sharad Pawar, the Union Minister for Agriculture and Food Processing Industries of India, addresses the audience at the official launch of the Borlaug Institute for South Asia (BISA), held in New Delhi, India on 5 October 2011. His speech highlighted the concerns of population growth both globally and especially in South Asia, in addition to rising food prices and unrest caused by food insecurity. He stated that “it would not be an overstatement to say that Norman Borlaug is a household name in India.” On a personal level, he also recalled his interaction with Dr. Borlaug in India in the 1960s
BISA will be a new, state-of-the-art, international agricultural research and development center, based in India and managed by CIMMYT. It will boost agricultural productivity by adapting wheat and maize varieties able to thrive despite the challenges of climate change, natural resource scarcity, diverse ecosystems, and increasing market demand. It will deliver elite wheat and maize germplasm that is high-yielding and robust—able to withstand drought, heat, diseases—and meets requirements for diversified cropping rotations and grain quality, and make it accessible to small seed companies so that they can offer quality, affordable seed to smallholder farmers. It will provide support in the use of modern biotechnology and bioinformatics tools and supply effective and profitable technologies and crop varieties for conservation and precision agriculture. BISA will have centers in three states, Punjab, Bihar, and Madhya Pradesh, each of which contains varied agro-ecological zones allowing for testing of a variety of maize and wheat cultivars suited to the equally varied environments of South Asia.
S. Ayyappan, Secretary of the Department of Agricultural Research and Education (DARE) of the Ministry of Agriculture of India and Director General of the Indian Council of Agricultural Research (ICAR), opened the launch ceremony with a welcome address. This was followed by speeches from Ramkrishna Kusmaria, Agriculture Minister of Madhya Pradesh, S. Sucha Singh Langah, Agriculture Minister of Punjab, and Minister Pawar. Thomas Lumpkin, CIMMYT Director General, delivered the closing remarks, saying “CIMMYT has been in India for 50 years. It’s time we laid down some roots.”
In addition to CIMMYT-India staff, the CIMMYT management committee, and its Board of Trustees, the ceremony was attended by representatives from CIMMYT’s sister institutions ILRI, IRRI, and Bioversity, as well as from the Allan Mustard Institute of the US Department of Agriculture and the private sector. The event was closed by a dinner and a speech by the Board of Trustees Chair, Sara Boettiger.
Photo credit: CIMMYT.
For more information about the launch, see CIMMYT's website at: www.cimmyt.org/en/front-page-tems/news2011/1166-new-borla....
For an overview of BISA, see: www.cimmyt.org/ru/about-us/partnerships/countries/doc_vie....
All G5s. 33 nodes, plus a couple others used as servers, backups, podcasting, testing and such. At ITC-ACHS at the University of Virginia.
Teacher Brian Gabert of Kent-Meridian High School at NWABR's 2011 Summer Bioinformatics Workshop. Click here for more about our Bio-ITEST program.
www.sk.ru/en Boston, USA 18JUN2012
Representatives from the Skolkovo Foundation participated in the 2012 BIO International Convention at the Boston Convention and Exhibition Center June 18-21. The conference, attended by pharmaceutical companies, teaching hospitals, venture capital firms and over 500 biotechnology companies, drew more than 15,000 attendees to the Boston area.
Mingle Media TV and Red Carpet Report host Paige Sullivan were invited to come back and cover the 2nd Annual Rebels with a Cause Gala at Paramount Studios honoring Larry Ellison with Jimmy Kimmel hosting and special guest performances by Barry Manilow and Pharrell Williams. This event supports the lifesaving research of David B. Agus, M.D. at USC’s Center for Applied Molecular Medicine.
Get the Story from the Red Carpet Report Team, follow us on Twitter and Facebook at:
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ABOUT THE USC CENTER FOR APPLIED MOLECULAR MEDICINE
The principal goal of the USC Center for Applied Molecular Medicine is the development of novel treatment strategies for cancer. The Center was implemented to enable a convergence of multiple disciplines to work on treatment and the care of patients with cancer. The program includes the clinical care of patients with cancer at the USC Westside Cancer Center in Beverly Hills and has team members with expertise spanning cancer biology, biochemistry, molecular biology, bioinformatics, computer science, electrical engineering, bioorganic chemistry, physics and applied mathematics. For information, visit camm.usc.edu/.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
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Follow our host Paige Sullivan on Twitter at twitter.com/PaigeSull
Gordon Moore was in a merry mood last night at a charity dinner. We swapped childhood stories about rockets and explosives. He used to mix his own nitroglycerin and dynamite.
We also spoke about the myriad industries that have been disrupted by the steady march of Moore's Law, from Tesla cars to synthetic genomics.
The non-linear exponentiation of technological capabilities is a fundamental and perpetual source of disruption that creates opportunities for entrepreneurship and new products. Apple could predict exactly when the price of hard drives and then flash memory would enable the iPod to disrupt the Sony Walkman business.
Moore’s Law drives electronics, communications and computers and has become a primary driver in drug discovery and bioinformatics, medical imaging and diagnostics.
More than a niche subject of interest only to chip designers, the continued march of Moore’s Law will affect all of the sciences, as they migrate from lab to simulation. Accurate simulation demands computational power, and once a sufficient threshold has been crossed, simulation acts as an innovation accelerant over physical experimentation. Many more questions can be answered per day.
NASA Ames recently shut down their wind tunnels. As Moore’s Law provided enough computational power to model turbulence and airflow, there was no longer a need to test iterative physical design variations of aircraft in the wind tunnels, and the pace of innovative design exploration dramatically accelerated.
Recent accuracy thresholds have been crossed in diverse areas, such as modeling the weather (predicting a thunderstorm six hours in advance) and automobile collisions (a relief for the crash test dummies), and the thresholds have yet to be crossed for many areas, such as protein folding dynamics.
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Mingle Media TV and Red Carpet Report host Paige Sullivan were invited to come back and cover the 2nd Annual Rebels with a Cause Gala at Paramount Studios honoring Larry Ellison with Jimmy Kimmel hosting and special guest performances by Barry Manilow and Pharrell Williams. This event supports the lifesaving research of David B. Agus, M.D. at USC’s Center for Applied Molecular Medicine.
Get the Story from the Red Carpet Report Team, follow us on Twitter and Facebook at:
www.facebook.com/RedCarpetReportTV
www.youtube.com/MingleMediaTVNetwork
ABOUT THE USC CENTER FOR APPLIED MOLECULAR MEDICINE
The principal goal of the USC Center for Applied Molecular Medicine is the development of novel treatment strategies for cancer. The Center was implemented to enable a convergence of multiple disciplines to work on treatment and the care of patients with cancer. The program includes the clinical care of patients with cancer at the USC Westside Cancer Center in Beverly Hills and has team members with expertise spanning cancer biology, biochemistry, molecular biology, bioinformatics, computer science, electrical engineering, bioorganic chemistry, physics and applied mathematics. For information, visit camm.usc.edu/.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
www.facebook.com/minglemediatvnetwork
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Follow our host Paige Sullivan on Twitter at twitter.com/PaigeSull
It has been a busy term for the 49Women in Science Committee, which was formed five years ago after identifying the need for supports and guidance for young women pursuing a career in STEM. Our fall 2022 student event was held on-campus on October 13. Students had the privilege of listening to guest speaker Dr. Fiona Brinkman, SFU professor in Bioinformatics and head of the Brinkman Lab. She shared her educational and career journey, inspiring those in attendance with what is possible.
Mingle Media TV and Red Carpet Report host Paige Sullivan were invited to come back and cover the 2nd Annual Rebels with a Cause Gala at Paramount Studios honoring Larry Ellison with Jimmy Kimmel hosting and special guest performances by Barry Manilow and Pharrell Williams. This event supports the lifesaving research of David B. Agus, M.D. at USC’s Center for Applied Molecular Medicine.
Get the Story from the Red Carpet Report Team, follow us on Twitter and Facebook at:
www.facebook.com/RedCarpetReportTV
www.youtube.com/MingleMediaTVNetwork
ABOUT THE USC CENTER FOR APPLIED MOLECULAR MEDICINE
The principal goal of the USC Center for Applied Molecular Medicine is the development of novel treatment strategies for cancer. The Center was implemented to enable a convergence of multiple disciplines to work on treatment and the care of patients with cancer. The program includes the clinical care of patients with cancer at the USC Westside Cancer Center in Beverly Hills and has team members with expertise spanning cancer biology, biochemistry, molecular biology, bioinformatics, computer science, electrical engineering, bioorganic chemistry, physics and applied mathematics. For information, visit camm.usc.edu/.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
www.facebook.com/minglemediatvnetwork
www.flickr.com/MingleMediaTVNetwork
Follow our host Paige Sullivan on Twitter at twitter.com/PaigeSull
Mingle Media TV and Red Carpet Report host Paige Sullivan were invited to come back and cover the 2nd Annual Rebels with a Cause Gala at Paramount Studios honoring Larry Ellison with Jimmy Kimmel hosting and special guest performances by Barry Manilow and Pharrell Williams. This event supports the lifesaving research of David B. Agus, M.D. at USC’s Center for Applied Molecular Medicine.
Get the Story from the Red Carpet Report Team, follow us on Twitter and Facebook at:
www.facebook.com/RedCarpetReportTV
www.youtube.com/MingleMediaTVNetwork
ABOUT THE USC CENTER FOR APPLIED MOLECULAR MEDICINE
The principal goal of the USC Center for Applied Molecular Medicine is the development of novel treatment strategies for cancer. The Center was implemented to enable a convergence of multiple disciplines to work on treatment and the care of patients with cancer. The program includes the clinical care of patients with cancer at the USC Westside Cancer Center in Beverly Hills and has team members with expertise spanning cancer biology, biochemistry, molecular biology, bioinformatics, computer science, electrical engineering, bioorganic chemistry, physics and applied mathematics. For information, visit camm.usc.edu/.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
www.facebook.com/minglemediatvnetwork
www.flickr.com/MingleMediaTVNetwork
Follow our host Paige Sullivan on Twitter at twitter.com/PaigeSull
Mingle Media TV and Red Carpet Report host Paige Sullivan were invited to come back and cover the 2nd Annual Rebels with a Cause Gala at Paramount Studios honoring Larry Ellison with Jimmy Kimmel hosting and special guest performances by Barry Manilow and Pharrell Williams. This event supports the lifesaving research of David B. Agus, M.D. at USC’s Center for Applied Molecular Medicine.
Get the Story from the Red Carpet Report Team, follow us on Twitter and Facebook at:
www.facebook.com/RedCarpetReportTV
www.youtube.com/MingleMediaTVNetwork
ABOUT THE USC CENTER FOR APPLIED MOLECULAR MEDICINE
The principal goal of the USC Center for Applied Molecular Medicine is the development of novel treatment strategies for cancer. The Center was implemented to enable a convergence of multiple disciplines to work on treatment and the care of patients with cancer. The program includes the clinical care of patients with cancer at the USC Westside Cancer Center in Beverly Hills and has team members with expertise spanning cancer biology, biochemistry, molecular biology, bioinformatics, computer science, electrical engineering, bioorganic chemistry, physics and applied mathematics. For information, visit camm.usc.edu/.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
www.facebook.com/minglemediatvnetwork
www.flickr.com/MingleMediaTVNetwork
Follow our host Paige Sullivan on Twitter at twitter.com/PaigeSull
Mingle Media TV and Red Carpet Report host Paige Sullivan were invited to come back and cover the 2nd Annual Rebels with a Cause Gala at Paramount Studios honoring Larry Ellison with Jimmy Kimmel hosting and special guest performances by Barry Manilow and Pharrell Williams. This event supports the lifesaving research of David B. Agus, M.D. at USC’s Center for Applied Molecular Medicine.
Get the Story from the Red Carpet Report Team, follow us on Twitter and Facebook at:
www.facebook.com/RedCarpetReportTV
www.youtube.com/MingleMediaTVNetwork
ABOUT THE USC CENTER FOR APPLIED MOLECULAR MEDICINE
The principal goal of the USC Center for Applied Molecular Medicine is the development of novel treatment strategies for cancer. The Center was implemented to enable a convergence of multiple disciplines to work on treatment and the care of patients with cancer. The program includes the clinical care of patients with cancer at the USC Westside Cancer Center in Beverly Hills and has team members with expertise spanning cancer biology, biochemistry, molecular biology, bioinformatics, computer science, electrical engineering, bioorganic chemistry, physics and applied mathematics. For information, visit camm.usc.edu/.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
www.facebook.com/minglemediatvnetwork
www.flickr.com/MingleMediaTVNetwork
Follow our host Paige Sullivan on Twitter at twitter.com/PaigeSull
Thomas Lumpkin (left), CIMMYT Director General, and S. Ayyappan, Secretary of the Department of Agricultural Research and Education (DARE) of the Ministry of Agriculture of India and Director General of the Indian Council of Agricultural Research (ICAR), shake hands after signing documents sealing the official launch of the Borlaug Institute for South Asia (BISA), held in New Delhi, India on 5 October 2011.
BISA will be a new, state-of-the-art, international agricultural research and development center, based in India and managed by CIMMYT. It will boost agricultural productivity by adapting wheat and maize varieties able to thrive despite the challenges of climate change, natural resource scarcity, diverse ecosystems, and increasing market demand. It will deliver elite wheat and maize germplasm that is high-yielding and robust—able to withstand drought, heat, diseases—and meets requirements for diversified cropping rotations and grain quality, and make it accessible to small seed companies so that they can offer quality, affordable seed to smallholder farmers. It will provide support in the use of modern biotechnology and bioinformatics tools and supply effective and profitable technologies and crop varieties for conservation and precision agriculture. BISA will have centers in three states, Punjab, Bihar, and Madhya Pradesh, each of which contains varied agro-ecological zones allowing for testing of a variety of maize and wheat cultivars suited to the equally varied environments of South Asia.
Ayyappan opened the launch ceremony with a welcome address that was followed by speeches from Ramkrishna Kusmaria, Agriculture Minister of Madhya Pradesh, S. Sucha Singh Langah, Agriculture Minister of Punjab, and Sharad Pawar, the Union Minister for Agriculture and Food Processing Industries of India. Lumpkin delivered the closing remarks, saying “CIMMYT has been in India for 50 years. It’s time we laid down some roots.”
In addition to CIMMYT-India staff, the CIMMYT management committee, and its Board of Trustees, the ceremony was attended by representatives from CIMMYT’s sister institutions ILRI, IRRI, and Bioversity, as well as from the Allan Mustard Institute of the US Department of Agriculture and the private sector. The event was closed by a dinner and a speech by the Board of Trustees Chair, Sara Boettiger.
Photo credit: CIMMYT.
For more information about the launch, see CIMMYT's website at: www.cimmyt.org/en/front-page-tems/news2011/1166-new-borla....
For an overview of BISA, see: www.cimmyt.org/ru/about-us/partnerships/countries/doc_vie....
Second major version of this. Removed two OpenArrays, added a screenshot from a Roche/454 sequencer (bottom right), added some QC bar graphs from the Illumina Genome Analyzer,cleaned up some layer overlaps, faded the Sanger sequence at the bottom, and added an instrument at the top left (as suggested by ADT image!nation in the comments to the previous version).
Whew! Sounds like a lot of effort, but it wasn't really. Good old Photoshop.
EDIT - the final version (subtly different to this one) has been chosen as part of the institutional art exhibition, and will be blown up to poster size for the show in June.
Mingle Media TV and Red Carpet Report host Paige Sullivan were invited to come back and cover the 2nd Annual Rebels with a Cause Gala at Paramount Studios honoring Larry Ellison with Jimmy Kimmel hosting and special guest performances by Barry Manilow and Pharrell Williams. This event supports the lifesaving research of David B. Agus, M.D. at USC’s Center for Applied Molecular Medicine.
Get the Story from the Red Carpet Report Team, follow us on Twitter and Facebook at:
www.facebook.com/RedCarpetReportTV
www.youtube.com/MingleMediaTVNetwork
ABOUT THE USC CENTER FOR APPLIED MOLECULAR MEDICINE
The principal goal of the USC Center for Applied Molecular Medicine is the development of novel treatment strategies for cancer. The Center was implemented to enable a convergence of multiple disciplines to work on treatment and the care of patients with cancer. The program includes the clinical care of patients with cancer at the USC Westside Cancer Center in Beverly Hills and has team members with expertise spanning cancer biology, biochemistry, molecular biology, bioinformatics, computer science, electrical engineering, bioorganic chemistry, physics and applied mathematics. For information, visit camm.usc.edu/.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
www.facebook.com/minglemediatvnetwork
www.flickr.com/MingleMediaTVNetwork
Follow our host Paige Sullivan on Twitter at twitter.com/PaigeSull
www.sk.ru/en Boston, USA 18JUN2012
Representatives from the Skolkovo Foundation participated in the 2012 BIO International Convention at the Boston Convention and Exhibition Center June 18-21. The conference, attended by pharmaceutical companies, teaching hospitals, venture capital firms and over 500 biotechnology companies, drew more than 15,000 attendees to the Boston area.
via ~jtl/PHOTOS
www.cs.manchester.ac.uk/assessment/prizes/
1984 - David Newton
1986 - Jean Alain Ah-Kee PhD 1989
1987 - Kevin Glynn
1988 - David Banks, Master Technologist, Hewlett Packard
1994 - Colin May
1995 - Mark Everingham, PhD, Lecturer, University of Leeds
1996 - Andrew Bardsley
1997 - Andrew Broad
2000 - Mark Kendrick
2001 - Alexander Brown
2002 - David Mackintosh
2003 - Sanne Abeln, PhD, Assistant Professor of Bioinformatics www.few.vu.nl/~abeln/
2004 - Matthew Winrow
2004 - Shahzad Younas
2006 - Fiona Goddard
2008 - Benjamin London, currently at UBS www.benlondon.co.uk/
2010 - Sergejs Aleksejevs
2012 - Jonathan Heathcote, jhnet.co.uk/
A major challenge of the Human Genome Project was "annotation", or making descriptive sense, of the raw DNA sequence. Output from an automated capillary sequencer, with each of the four DNA bases labeled a different colour, forms the raw data. These data are then processed with various annotation "pipelines", including assembly of the raw reads into larger "contigs" and ultimately a finished genome sequence.
Represented here is the transition from primary sequence data (left) through the "brain filtering" and computer processing of bioinformatics (right). The image has been treated with a simulation of the "bleach bypass" developing technique used on photographic film in the pre-digital, genome project era.
[The preceding pompous description goes with this piece of "art", submitted for consideration as part of a gallery exhibit for an institutional fundraiser. I can call it pompous with impunity, because I wrote it.]
Licensed to the U.S. National Institute of Dental and Craniofacial Research (NIDCR) for use in this article:
www.nidcr.nih.gov/ScienceSpotlight/InterviewsbyTopic/Head...
Some screenshots from a tool that I am building to visualize flue genomic data.
For more information, read this blog post:
blog.blprnt.com/blog/blprnt/open-science-h1n1-processing-...
Mingle Media TV and Red Carpet Report host Paige Sullivan were invited to come back and cover the 2nd Annual Rebels with a Cause Gala at Paramount Studios honoring Larry Ellison with Jimmy Kimmel hosting and special guest performances by Barry Manilow and Pharrell Williams. This event supports the lifesaving research of David B. Agus, M.D. at USC’s Center for Applied Molecular Medicine.
Get the Story from the Red Carpet Report Team, follow us on Twitter and Facebook at:
www.facebook.com/RedCarpetReportTV
www.youtube.com/MingleMediaTVNetwork
ABOUT THE USC CENTER FOR APPLIED MOLECULAR MEDICINE
The principal goal of the USC Center for Applied Molecular Medicine is the development of novel treatment strategies for cancer. The Center was implemented to enable a convergence of multiple disciplines to work on treatment and the care of patients with cancer. The program includes the clinical care of patients with cancer at the USC Westside Cancer Center in Beverly Hills and has team members with expertise spanning cancer biology, biochemistry, molecular biology, bioinformatics, computer science, electrical engineering, bioorganic chemistry, physics and applied mathematics. For information, visit camm.usc.edu/.
For more of Mingle Media TV’s Red Carpet Report coverage, please visit our website and follow us on Twitter and Facebook here:
www.facebook.com/minglemediatvnetwork
www.flickr.com/MingleMediaTVNetwork
Follow our host Paige Sullivan on Twitter at twitter.com/PaigeSull
Classical Indian dancing marks the official launch of the Borlaug Institute for South Asia (BISA), held in New Delhi, India on 5 October 2011.
BISA will be a new, state-of-the-art, international agricultural research and development center, based in India and managed by CIMMYT. It will boost agricultural productivity by adapting wheat and maize varieties able to thrive despite the challenges of climate change, natural resource scarcity, diverse ecosystems, and increasing market demand. It will deliver elite wheat and maize germplasm that is high-yielding and robust—able to withstand drought, heat, diseases—and meets requirements for diversified cropping rotations and grain quality, and make it accessible to small seed companies so that they can offer quality, affordable seed to smallholder farmers. It will provide support in the use of modern biotechnology and bioinformatics tools and supply effective and profitable technologies and crop varieties for conservation and precision agriculture. BISA will have centers in three states, Punjab, Bihar, and Madhya Pradesh, each of which contains varied agro-ecological zones allowing for testing of a variety of maize and wheat cultivars suited to the equally varied environments of South Asia.
Ayyappan opened the launch ceremony with a welcome address that was followed by speeches from Ramkrishna Kusmaria, Agriculture Minister of Madhya Pradesh, S. Sucha Singh Langah, Agriculture Minister of Punjab, and Sharad Pawar, the Union Minister for Agriculture and Food Processing Industries of India. Thomas Lumpkin, CIMMYT Director General, delivered the closing remarks, saying “CIMMYT has been in India for 50 years. It’s time we laid down some roots.”
In addition to CIMMYT-India staff, the CIMMYT management committee, and its Board of Trustees, the ceremony was attended by representatives from CIMMYT’s sister institutions ILRI, IRRI, and Bioversity, as well as from the Allan Mustard Institute of the US Department of Agriculture and the private sector. The event was closed by a dinner and a speech by the Board of Trustees Chair, Sara Boettiger.
Photo credit: CIMMYT.
For more information about the launch, see CIMMYT's website at: www.cimmyt.org/en/front-page-tems/news2011/1166-new-borla....
For an overview of BISA, see: www.cimmyt.org/ru/about-us/partnerships/countries/doc_vie....
The Northwest Association for Biomedical Research was excited to share with teachers our bioinformatics program, New Frontiers in Bioinformatics and Computational Biology funded by the National Science Foundation. The two-day workshop began in the Seattle research center of Novo Nordisk A/S and ended at Shoreline Community College, which features a Biotechnology Lab Specialist Program.