Good news comes from the development of the new crown pneumonia vaccine

Novel coronavirus pneumonia vaccine is coming A novel coronavirus vaccine candidate developed by the National Institute of allergy and infectious diseases (NIAID) and drug manufacturer Moderna has been successfully developed in February 24th The first human trial will be conducted before the end of April, according to the Wall Street journal Meanwhile, novel coronavirus has learned from the Tianjin University that the golden sea team of the school of life sciences has successfully developed a new oral vaccine for coronavirus It is reported that Professor Huang Jinhai has taken 4 times oral dose of new crown vaccine without any side effects Vaccine development is much faster than expected, according to Xu Nan, Vice Minister of science and technology, who previously disclosed that "the fastest vaccine will be declared for clinical trials in late April" However, it should be noted that, like new drug development, vaccine development and marketing is a relatively time-consuming process At present, vaccine research and development are only in the experimental stage, and there is still a long time to the real large-scale production and marketing The novel coronavirus pneumonia vaccine developed in novel coronavirus pneumonia is two flowering According to the Wall Street journal, American Pharmaceutical Company Moderna had predicted that the development of the new crown vaccine may take more than 3 months However, the vaccine was applied to the new crown pneumonia in the first month of the attack and transported to the National Institute of allergy and infectious diseases In fact, the mRNA technology platform created by Moderna helps it become one of the world's leading mRNA companies In the process of developing new coronavirus vaccine, Moderna adopts mRNA technology It should be noted that Moderna can not develop mRNA vaccine without the assistance of Chinese scientists Shortly after the outbreak, Chinese scientists quickly identified the whole genome sequence of the new coronavirus and shared this information with the World Health Organization on January 11 to help global research institutions develop drugs It is reported that Moderna will be tested on 20-25 healthy volunteers before the end of April, and the specific results will be published in July or August In China, the golden sea team is looking for partners, hoping to promote the vaccine to clinical as soon as possible and play a role in epidemic prevention and control According to the novel coronavirus S protein, the vaccine is produced by using food safety Saccharomyces cerevisiae as the carrier The novel coronavirus novel coronavirus S protein (Spike protein, spike protein) can bind to the host's receptor, and is a key protein that determines the susceptibility of the virus to invasive cells It is also a key target for the development of new coronavirus vaccines and drugs for the prevention and treatment Using food grade safety yeast as the host to develop biological control agents, the vaccine is immunized by oral route, which has the advantages of stimulating local mucosal immunity, regulating immune homeostasis, convenient use, good safety and rapid production capacity Golden sea told reporters that its team has developed the oral vaccine and made some samples "At present, it is inferred that the vaccine is effective because similar animal vaccine experiments have been carried out in the early stage, which has proved to be effective In view of the effectiveness of the oral vaccine, we must continue to carry out experiments including human experiments in the future Only after passing the experiments can we prove the effectiveness of the oral vaccine " At present, the team is only completing some technical and manufacturing preliminary work of the vaccine, said Goldsea The follow-up clinical application of the vaccine, including toxicology experiments, and some pharmacodynamic experiments, should be evaluated at all levels of the country Finally, it needs to be approved, hospital cooperation, and effect evaluation, so that it can be widely used at two levels and three levels Novel coronavirus pneumonia vaccine is the most difficult one to develop The statistics of China's vaccine industry association were listed before that As of February 11th, 18 enterprises were developing new crown pneumonia vaccine On February 21, the University of Queensland, Australia, said researchers used molecular tweezers technology to develop the first candidate vaccine in the laboratory, and will enter key pre clinical tests immediately after passing the final validation The novel coronavirus biotech Co., Ltd announced in February 24th that it would launch research and development cooperation with GSK to promote the research and development of its protein based new coronavirus vaccine "COVID-19 S- trimer" Facing the new coronavirus, the world has given the fastest speed in vaccine research and development, but it will take a long time from the successful research and development to the official launch According to Anthony Fauci, director of the National Institute of allergy and infectious diseases, further research and regulatory hurdles will follow a successful trial, which means that the coronavirus vaccine will not be ready for widespread distribution until at least next year Golden sea also pointed out that the vaccine development and marketing is a rigorous and long process At present, the team is actively arranging for animal toxicology, immune efficacy, pilot production and other evaluations It is hoped that qualified enterprises and units will cooperate to complete the follow-up evaluation process of the vaccine, accelerate the clinical verification and promotion of the vaccine, and help prevent and control the epidemic situation According to the data, in 2014, the Ebola epidemic broke out in Africa Although after the outbreak, major scientific research institutions and pharmaceutical companies around the world competed for a breakthrough in vaccine development, the first Ebola vaccine declared by MSD was approved for use in the United States and the European Union by the end of 2019, and the development and approval of Ebola vaccine took up to five years It can be seen that it will take longer for a vaccine to be put on the market According to the information obtained by China Science Daily, the Ministry of science and technology has approved and supported the research and development of five vaccines, including inactivated vaccine, attenuated vaccine, nucleic acid vaccine, vector vaccine and recombinant protein vaccine The research and development of these vaccines are in full swing Yan Jinghua told China Science Daily that the above five vaccine strategies have their own characteristics and advantages and disadvantages, but the ultimate goal is to develop new crown vaccine products that meet the requirements of effectiveness and safety as soon as possible Yan Jinghua said that the specific vaccine developed first and which vaccine has better safety and effectiveness can only be known after the final evaluation, "which is one of the reasons why the five vaccines of the Ministry of science and technology have support." However, it can be determined that vaccine research and development is a systematic project From laboratory samples to market, it has to go through many links, such as vaccine sample preparation, animal experiment, pre clinical production process research and development, clinical experiment, effectiveness and safety evaluation It usually takes several years in normal times, and at least several months in unusual times to prepare and repeatedly verify, "and It's not done overnight In addition, Qu Qiang (Ph.D in clinical pharmacology, Department of pharmacy, Xiangya Hospital, Central South University), Wang ruoguang (M.D., postdoctoral in biology, Changsha ruoguang Medical Research Center) also mentioned that in the scheme of entecavir, entecavir can be taken for several years or even more than 10 years And pregnant women can use it, which shows good safety So far, all novel coronavirus pneumonia (COVID19) drugs are either beyond label or clinical trial, mainly with support and symptomatic treatment There is no medicine available for suspected cases and high-risk groups, and there are various medicines purchased by themselves Entecavir is an antiviral drug of hepatitis B virus (HBV) It is a guanine nucleoside analogue It has an inhibitory effect on HBV polymerase Through phosphorylation to active triphosphate, entecavir triphosphate can inhibit all three activities of viral polymerase (reverse transcriptase) by competing with deoxyguanosine triphosphate, a natural substrate of HBV polymerase: ① activation of HBV polymerase; ② formation of reverse transcriptional negative chain of pre genomic mRNA; ③ synthesis of positive chain of HBV DNA Entecavir is a virus specific polymerase The RNA replication process required for RNA virus replication and the reverse transcription process required for retrovirus replication will not occur in human cells Therefore, if the virus wants to replicate, it must use its own polymerase, such as RNA replicase (RdRp) of RNA virus and reverse transcriptase (RT) of retrovirus Nucleosides and nucleotides are the components of viral nucleic acids Whether human DNA polymerases, RNA polymerases, or RdRp and RT of viruses, the principle of their nucleic acid synthesis is the same They are all synthesized along the 5 'end to 3' end of nucleic acids The nucleoside (acid) analogues prevent virus replication by selectively inhibiting the virus's polymerase In our preliminary analysis of antiviral effect of entecavir, since there is no RdRp structure of 2019 ncov, 3D modeling is conducted after homology analysis of RdRp structure of SARS virus and RdRp protein sequence of 2019 ncov After molecular docking with entecavir triphosphate, it is found that it is well bound to the active pocket of RdRp (Figure 1) Figure 1: molecular docking diagram of entecavir triphosphate and RdRp From these known molecular pharmacological mechanisms, entecavir may have broad-spectrum antiviral effect, not only for HBV We often use entecavir in clinical treatment of viral respiratory infection, the effect is significant At present, among more than 500 cases of covid19 patients in Hubei Province, only one patient took entecavir, the prescription time was at the beginning of January, and then stopped taking it However, the medical staff, some grassroots doctors, or high-risk groups who support Hubei Province, currently use entecavir to prevent covid19, there is no case of infection No one was diagnosed as covid19 in the suspected population More clinical experiments are needed to confirm the clinical effect of entecavir, and relevant work is under way The ultimate goal is to be safe and effective in five kinds of vaccines, inactivated vaccines and attenuated vaccines are more common, recombinant protein vaccines and nucleic acid vaccines are relatively new forms, especially nucleic acid vaccines represented by DNA vaccines and mRNA vaccines, because they do not need in vitro expression and other steps in the early stage of research and development, they are promoted rapidly However, Yan Jinghua said that at present, there is no nucleic acid vaccine for infectious disease prevention and control in the world, and the formulation of relevant production process and quality control standards may "take a long time" in the later stage of vaccine preparation Compared with inactivated vaccine and attenuated vaccine, one of the advantages of recombinant protein vaccine is that it expresses the most important antigen part of the virus as protein component, which is safer in use and production process; however, it also has limitations - most recombinant protein vaccines need the help of adjuvants (compatibility) to play the immunogenicity "No vaccine can be said to be absolutely good or bad It needs to be customized." Yan Jinghua said that the choice should be based on the characteristics of different viruses "The ultimate goal is to be safe and effective, no matter what path to choose.".