The team led by researcher Shi Zhengli of the Institute is an authority in the field of bat virus research, and also a team to tackle the source of SARS (severe acute respiratory syndrome) virus in China. However, with the progress of the epidemic, rumors such as laboratory virus leakage and man-made new virus began to envelop Wuhan Virus Research Institute and Shi Zhengli and others.
On the afternoon of February 2, Shi Zhengli responded in the circle of friends: the 2019 new coronavirus is the punishment of nature for the uncivilized living habits of human beings. I, Shi Zhengli, have nothing to do with the laboratory with my life guarantee. In an interview with science, Peter daszak, a former partner of Shi Zhengli and disease ecologist of the American non-profit organization eco Health Alliance, also said that whenever new diseases and viruses appear, there will be conspiracy theories such as laboratory leakage or Bioengineering and manufacturing, which is shameful!
For the current many guesses, a biology scholar interviewed by a surging news reporter said, my view is based on the reasonable speculation and academic research based on the existing data. If there is, if there is, there is no, scientific research cannot be assumed without foundation.. He doesnt think the new coronavirus originated from Shi Zhenglis lab, but he also said, its not a scientific attitude that we cant guarantee my life
Wuhan Virus Research Institute of Chinese Academy of Sciences was founded in 1956. It is a comprehensive research institution specialized in basic virology research and related technological innovation. It has the first Biosafety (Level 4) laboratory put into formal operation in China.
According to the official website, Shi Zhengli is currently the director of new infectious diseases research center of Wuhan Institute of Virology, deputy director of Wuhan National biosafety laboratory (Level 4), director of Biosafety Level 3 laboratory, etc. He has been engaged in the etiology research of new viruses for a long time, and has rich research experience in the etiology, molecular epidemic and infection mechanism of viruses transmitted by wild animals. Shi Zhengli is also the leader of the expert group for the emergency research of 2019 new pneumonia emergency science and technology research project in Hubei Province.
On the same day, nature launched two new coronavirus related papers. In addition to Shi Zhenglis team, another one was completed by Zhang Yongzhen, a researcher of the Institute of infectious disease prevention and control of China CDC and a part-time professor of Shanghai (affiliated to Fudan University) public health clinical center.
New coronavirus 2 years ago? In fact, pigs are infected
Where does the new coronavirus come from? When does it start to infect people? Social media speculation was a step ahead of the scientific conclusion of these issues. A paper published by Shi Zhengli and others in 2018 has become one of the bases for netizens to guess, which is believed to have appeared as early as two years ago.
On April 5, 2018, nature published a study online. In addition to Shi Zhengli, Wuhan, the corresponding authors of the study include Wang Linfa, director of the Institute of emerging infectious diseases, Duke Singapore National University School of medicine, Peter daszak, President of the Ecohealth alliance, Tong Yigang, Institute of microbial epidemiology, Academy of Military Medical Sciences, and Huazhong Agricultural University Ma Jingyun, School of animal science. This achievement was reported in detail by surging journalists. At that time, another new coronavirus was found, but not this time.
The clue of this paper is that since October 28, 2016, a fatal pig epidemic has started in a pig farm in Qingyuan, Guangdong Province. It is only more than 100 kilometers away from Foshan, Guangdong Province, where SARS broke out in 2002.
The team finally cracked the pig epidemic as acute diarrhea syndrome (SADS), the disease causing sads coronavirus or a new type of coronavirus.
The sequence consistency of sads coronavirus gene and hku2 coronavirus collected from the diseased piglets small intestine was 95%. Hku2 was first found in Chinese Rhinolophus in Hong Kong and Guangdong, but the consistency of spike protein gene sequence between them was only 86%.
In an interview with www.thepaper.cn, Zhou Peng, co-author of the paper and researcher of Wuhan Institute of Virology, Chinese Academy of Sciences, said that coronaviruses use spike protein to invade cells, just like key and lock , which rely on the binding of spike protein and receptor on cell surface, and then enter cells and infect cells successfully But if the spike protein is highly variable, it cant use the receptor
Zhou Peng stressed at that time, for this reason, 86% of the data are consistent. We believe that the relationship between sads coronavirus and hku2 coronavirus is not the most direct. We have had SARS experience before, and finally found that the consistency with the spike protein of SARS reached 97% and 98%, so that we can directly use the human receptor to infect successfully.
For these reasons, the team continued to look for sources and screened 591 bat anal swabs collected by the team from seven different locations in Guangdong Province from 2013 to 2016. Among them, 58 (9.8%) bat anal swabs were positive, and all of them came from the Chinese Rhinolophus. High throughput sequencing showed that the size (27.2kb) of this coronavirus (sadsr coronavirus for the time being) and sads coronavirus from the Chinese Rhinolophus is similar, and the overall sequence consistency is between 96% and 98%. More importantly, the sequence consistency of spike proteins (162149 and 141388, respectively) was more than 98%.
Zhou Peng said at that time, our current conclusion is that the discovery of sadsr coronavirus in bats may be the ancestor of this new virus found in sick pigs, but the same direct source of hku2 coronavirus and sadsr coronavirus in bats may come from an ancestor.
At that time, the research team also linked sads and SARS in the paper. Both of them originated not far from each other, and both of them originated from Rhinolophus, and in practice, we found that the same Rhinolophus carried SARS like coronavirus and this swine disease virus at the same time. And the coronavirus recombination is very strong, just like building blocks, my modules are put in your place, your modules are put in my place, maybe in the future, what will be composed of again.
However, unlike SARS, the teams newly discovered SARS coronavirus had not been found to cause death by the time of publication.
At that time, it was mentioned in the paper that in order to investigate the possible human animal transmission, the research team used antibody detection method to analyze the serum samples of 35 pig farm workers who were in close contact with the disease, and no one was positive for sads coronavirus.
Shi Zhengli also said at the time, through this work, we would like to remind that whether it is aquaculture or public health, we should prevent the spread of these pathogens from these wild animals to human society in advance. In fact, these pathogens exist for a long time in nature. As long as we isolate, prevent or diagnose these pathogens at an early stage, we can completely avoid such a large-scale outbreak of infectious diseases.
Especially after the outbreak of SARS, there is a consensus in our country, including around the world, that we want to move forward the front of new infectious diseases, she said
In fact, the virologists including Shi Zhengli and other teams, their academic papers over the years, not only reflect that they are constantly responding to new infectious diseases around the world, but also reflect that they are trying to find out more laws about the virus and prepare for the next unknown epidemic. Although such preparations are often seen as having little to gain in actual combat, the cunning nature of the virus has so far left humans in a bad position.
The Indian paper said that the virus is artificially spliced and has HIV fragments, which has been withdrawn by the peer review
If the speculation that new coronavirus has been around for a long time is only for some people who do not have professional knowledge, a paper on biorxiv, the website of biological preprint, launched on January 31, triggered a wave of academic discussion.
Biorxiv is a free online archive and distribution service for unpublished preprints in life sciences, operated by the renowned non-profit research laboratory, Cold Spring Harbor Laboratory (CSHL). Generally speaking, the preprint is the completed draft of the scientific research paper, which is uploaded to the public database by the author. If the paper has been modified subsequently, it can also be uploaded continuously, but the old version will continue to exist, and the paper after the preprint is published can still be submitted to the Journal.
It is worth noting that before biorxiv publishes preprints online, articles are not peer reviewed, edited, or typeset.
This paper is from the research team of Delhi University and Indian Institute of technology. They compared the spike protein sequences of new coronavirus and SARS, and found that the spike protein of new coronavirus has four independent short peptide segments (6-12 amino acids left and right) more than the homologous protein of SARS virus. The authors thus point out that the four extra short peptide segments are unique to the new coronavirus, but not to other coronaviruses.
After the comparison and search in the database, it is concluded that the short peptide segments of these four segments are highly similar to the gp120 and Gag proteins in HIV-1. The authors think that this is not accidental. Through some 3D simulation of the structure, they speculate that these extra short peptide segments may be related to the binding of new coronavirus and its receptor.
In particular, the Indian team pointed out in the abstract of the paper that this is unlikely to happen accidentally in nature, and wrote again in the conclusion part, the unusual similarity between the spike protein of new coronavirus and HIV-1gp120 and Gag protein is unlikely to be accidental.
This paper led some conspiracy theorists to think that the new coronavirus originated from the laboratory.
But this article was quickly criticized by other professional scholars. Trevor Bedford, an associate professor in the Department of medicine and genomics at the University of Washington and an expert in bioinformatics at the Fred Hutchinson Cancer Research Center, tweeted the results of his own repeat alignment. He confirmed that these short insertion sequences do exist in the new coronavirus, but they can match the sequences of many species, most of which are not even viruses. Indian scholars claim that the unique HIV protein is not at the forefront of sequence comparison.
Xue Yu, a professor in the Biomedical Engineering Department of the school of life science and technology of Huazhong University of science and technology, said in an interview with surging journalists that he did not believe that the new coronavirus originated in the laboratory. On the afternoon of February 5, Xue Yu also elaborated his personal views on Science Blog.
Xue Yu believes that in all kinds of articles questioning whether the new coronavirus can come from the laboratory, the highest level is the founder and CEO of the Institute for pure and applied knowledge (IPak). James Lyons Weiler posted two technical posts in English on the Internet.
Xue said, he guessed that it originated from the laboratory, and the main evidence is that he found a 1378 bp insertion fragment that only existed in the new coronavirus, but not in other viruses, that is, ins1378 as he defined it. All his later conjectures are based on this premise.
What I did was to submit the sequence provided by him to the database, and found that ins1378 had similar fragments in many coronaviruses, which indicated that this sequence was not exclusive to the new crown, and all the assumptions made by James based on this fragment were not tenable. Xue Yu said.
Xue Yu also stressed that if the new coronavirus originated from ratg13 leaked in the laboratory, the leakage event should be at least 6.6 years ago, and a large number of virus strains between 2019-ncov and batcovratg13 with higher similarity to 2019-ncov must be found in the field.
Of course, it has also been suggested that laboratory culture conditions may accelerate the rate of virus mutation. Xue Yu once again stressed to the surging news that for the mutation rate of the new crown virus, the more rigorous estimate is about 1 / 3 of the mutation rate I used, so I have overestimated the mutation rate of the new crown as much as possible, that is, to prevent others from doing articles in this place.
He also said: it should be noted that the current analysis shows that the evolution rate of 2019-n cov is relatively low. Some researchers estimate that the mutation rate of 2019-ncov is 2.067 u00d7 10 ^ - 4 bases / site / year (http://viral.org/t/temporal-signal-and-the-evolutionary-rate-of-2019-n-cov-using-47-genes-collected-by-feb-01-2020 / 379). After conversion, it is about 6 genomes per year The mutation rate of the base is much lower than I assumed. In addition, some scholars use different models to estimate that the mutation rate of 2019-ncov is about 0.42x10 ^ - 3 u2013 1.89x10 ^ - 3, which is smaller than what I used. Therefore, we estimate that 2019-ncov mutates about 90 base sites every year, which can be considered as the upper limit.
Xiang Yan, a lifelong professor in the Department of Microbiology and immunology at the San Antonio Medical Center of Texas State University, also pointed out in a review that, combined with the assumed mutation rates of other coronaviruses, ratg13 and ncov-2019 may have a common ancestor 25 to 65 years ago.
It is worth mentioning that the aforementioned Indian team has removed the above-mentioned papers that caused the storm. This is the initial study, one of the authors wrote on the biorxiv platform. We have no intention of providing raw materials for conspiracy theory. Although we respect the criticism and comments of scientific research colleagues in biorxiv and other places, this story has been explained and shared in different ways on social platforms and news media. In order to avoid further misunderstanding and confusion around the world, we decided to withdraw the preprint and submit the revised version after re analysis.
Development of SARS transgenic virus? Shi Zhengli is only the 14th author, and the experiment is conducted in the United States
One of the bases surrounding Shi Zhenglis laboratory as the source of virus also includes another paper published in nature medicine in November 2015.
In this paper, the team selected the bat coronavirus shc014 strain which is the closest to the SARS coronavirus sequence for virus transformation, and then used for a series of studies.
As Zhou Peng said before, whether the main key spike protein of coronavirus infects people can use ACE2 receptor depends on whether it has evolved to infect people. Similarly, although shc014 is highly homologous with SARS coronavirus, the sequence of shc014 spike protein is different from that of SARS, so it is inferred that shc014 spike protein cannot infect human cells.
The team used a reverse genetics system for SARS coronavirus to generate and identify chimeric viruses that express shc014 spike protein in the skeleton of SARS coronavirus, except for a mouse adapted SARS coronavirus. Reverse genetics is a genetic research method to determine the function of a gene by studying its phenotype through site mutation.
The results showed that group 2B, which encodes shc014 spike protein in the skeleton of SARS coronavirus, could effectively utilize multiple homologues of ACE2 receptor of SARS and proliferate in primary human respiratory cells.
Through the animal experiment of infecting mouse model, the research team found that there was a significant difference between SARS virus and modified chimeric virus. SARS virus soon caused mice to lose weight and died four days after infection. Under the same virus titer (104pfu), shc014-ma15 could cause weight loss, but it was not fatal. Compared with SARS virus, the infection of chimeric virus to respiratory tract is much weaker. This shows that the virulence of the modified SARS virus has decreased a lot.
In addition, for mice with ACE2 deficiency, the modified SARS virus can not induce any symptoms, which shows that ACE2 is necessary for the infection of SARS virus.
After the content of the paper is clear, what work does researcher Shi Zhengli of Wuhan virus institute take charge of? In fact, there are 15 authors in the paper, Shi Zhengli is the 14th and not the corresponding author.
In the last part of the paper, the authors contribution defined the division of labor. Shi Zhengli only provided the sequence of shc014 spike protein, and did not participate in the experiment or write the paper.
In addition to Shi Zhengli, Ge Xingyi, another researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences, was responsible for the pseudo experiment (a pre experiment).
The first author of this paper is vineetd, Professor of Microbiology and immunology, University of Texas Medical School. Menachery was responsible for the design, coordination and execution of the experiment, as well as the analysis and writing of the manuscript. The design and implementation of the experiment were also carried out in the laboratory of the University of North Carolina, Chapel Hill.
The teams study has raised questions about whether the new virus will leak from the lab? A report written in 2015 by Declan Butler, a senior reporter of nature, was also intercepted to support similar queries. For example, Simon Wain Hobson, a virologist at the Pasteur Institute in Paris, France, points out that if the virus escapes, no one can predict its path of transmission.
It is worth noting that Richard ebright, a molecular biologist at Rutgers University and director of the laboratory of Waxman Institute of Microbiology, explicitly opposed the rumor that the virus has been artificially designed and transformed. The genome of the virus has been sequenced and there is no reliable evidence that the virus was designed artificially.
However, he said that the possibility of the outbreak entering the population through laboratory accidents could not be ruled out at present.
As for the human leakage, Xiang Yan also pointed out in the previous comments that ratg13 was detected by Shi Zhengli in bats in Yunnan Province a few years ago, but they did not have the live virus and full sequence of ratg13 before. He believes that 2019 ncov is a new virus that has never been seen before. At present, there is no bat coronavirus ratg13 that is closest to 2019 ncov in the laboratory. It is groundless to say that 2019 ncov is leaked from the laboratory.
In response to caixin.com, Shi Zhengli said, conspiracy theorists dont believe in science. I hope the national professional department will investigate and give us a clean slate.
In fact, the aforementioned virologist Hobson is considered to be in the critical camp of virus functional acquisition research (GoF). The so-called functional acquisition research of virus refers to the increase of virulence, transmissibility or host range of pathogens in the laboratory to study the characteristics of virus and evaluate emerging infectious diseases. This research method has different opinions among American scientists.
Ebright holds a similar view, saying that the United States and China have spent millions of dollars on bat coronavirus monitoring and bat coronavirus function acquisition research. If these research funds are used to develop coronavirus vaccines and antiviral drugs, rather than being used mistakenly to monitor coronavirus and function acquisition research, there may be vaccines or antiviral drugs now Things to deal with the current epidemic.
However, in the last part of the paper, published in nature medicine, it is also pointed out that attention must be paid to the background of the research: the U.S. government has imposed a moratorium on functional access research, but the production of chimeric viruses such as shc014-ma15 is not expected to increase the pathogenicity. In October 2013, the National Institutes of Health (NIH) suspended funding for all such studies, but before the ban, NIH also believed that the risk of the experiment did not reach the level of suspension, allowing it to continue during the agencys review, and finally to be published.
For the purpose of this paper, the abstract part explicitly mentioned that the emergence of severe acute respiratory syndrome coronavirus (SARS CoV) and Middle East respiratory syndrome (mers COV) highlighted the threat of virus cross species transmission events, and even led to the outbreak in human society. The researchers studied the potential of SARS like virus shc014-cov, which is currently prevalent in Rhinolophus sinensis, to become a human disease.
Is the outbreak a laboratory virus leak? Researcher: I guarantee my life
Before that, there were various versions of rumors on the Internet, which more or less associated the outbreak with the leakage of laboratory virus samples from domestic scientific research institutions.