Friday, March 13, 2020

Shi Zhengli : Unexpect SARS-like coronavirus cross-species infection will occur in Wuhan

Reporters : Deng Mushen, Yang Ru
Publisher : Caixin.com
Ref : http://science.caixin.com/2020-03-10/101526667.html
Translation, editing : Gan Yung Chyan
                                 / KUCINTA SETIA

Image : A horseshoe bat is probably the natural host of SARS-CoV-2. Picture courtesy of Wikiwand.

It has been more than two months since the outbreak of COVID-19 (covid, in short), and the natural host of the SARS-CoV-2 (covi, in short) is considered to be probably a bat, but who the intermediary host is still a mystery. 

In the evening of 9 March 2020, Shi Zhengli, a researcher at the Wuhan Institute of Virology of the Chinese Academy of Sciences, said in an online popular science lecture entitled" Know Yourself and Know Yourself-Understanding New Coronaviruses "organized by Intellectuals. She said, "In 2018, I judged that cross-species infection of bat-derived SARS-like coronavirus will be a high probability event, but I did not expect it to happen at the end of 2019,  in the city where I live (Wuhan). "



Shi Zhengli is the Director of the Key Laboratory of Emerging and Severe Pathogens and Biosafety of the Chinese Academy of Sciences, Director of the Emerging Infectious Diseases Research Center of the Wuhan Institute of Virology, and the leader of the emergency expert group of the "2019 New Pneumonia Emergency Science and Technology Project" of Hubei Province Science and Technology Department.  After the covid outbreak, Shi Zhengli's team published an article "The discovery of a new coronavirus and its possible bat origin" on the bioprint preprint platform bioRxiv on 23 January 2020. The study showed that the genetic sequence identity of the new coronavirus and the 2003 SARS-CoV virus was 79.5%, and that it was 96% identical to the RaTG13 coronavirus found in Yunnan chrysanthemum horseshoe bats, indicating that its natural host is likely to be bats. On 3 February, this paper was published in the top international academic journal Nature. 

However, at the critical moment of the covid pandemic, Shi Zhengli and the Wuhan Institute of Virology have repeatedly fallen into conspiracy theoretic storms. Zhengli responded below.

"Every new outbreak of an infectious disease is understandable because we do not understand the new virus, we do not understand its pathogenic mechanism, it is easy to cause panic, and it generates all kinds of untrue information."

Shi Zhengli also responded to the question " whether the special site of covi has been artificially inserted". She mentioned that there is a special site PRRA in the gene fragment of the new coronavirus spike protein, which has not been previously found in bat coronavirus. So some people suspect that this site was inserted artificially. However Chinese scientists have recently published a preprinted paper saying that this site was also found in a coronavirus sequence of bats. "This shows that these sites were not artificially inserted, but were originally found in the bat population." (See https://staygate.blogspot.com/2020/03/restriction-site-insertion-event-not.html) 

Cormorant coronaviruses are a class of RNA viruses that are divided into four genera: α, β, γ, and δ. They can infect many mammals such as bats, pigs, cattle, cats, dogs, marten, camels, mice, hedgehogs, and humans. In the lecture that night, Shi Zhengli combined with the phylogenetic tree analysis of the coronavirus full-length S protein gene. Among the subbeams of the coronavirus β genus Sabecovirus to which the coronavirus belongs, the diversity of the virus is very wide, combined with its surface spike protein gene The analysis can be further divided into 4 clusters, among which cluster 1 includes SARS coronavirus and several bat SARS-like coronaviruses; cluster 3 includes pangolin coronavirus, neocoronavirus and bat-derived coronavirus RaTG13. Clusters 2 and 4 are also from bats.

The SARS coronavirus of cluster 1 and the SARS-CoV-2 of cluster 3 have infected species before infecting humans. Shi Zhengli's team wants to know what the more detailed changes of the coronaviruses of cluster 1 and cluster 3 are, so that the virus can be infected across species "So we have to look at some of the finer sequences of their S proteins," she said. The result of the SARS virus research that year was that it can use human ACE2 (angiotensin-converting enzyme 2) as a receptor, and further analyze with ACE2 binds the tightest viral S protein receptor binding motif, and the gene sequence of this region can be divided into two clusters. One cluster includes SARS virus, covi, pangolin coronavirus, RaTG13, and two bats. Coronaviruses are of origin WIV1 and SHC014. Previous studies have found that WIV1 and SHC014 are capable of using ACE2 as a receptor, and it is now known that both SARS virus and covi also use ACE2 as a receptor.

"We speculate that pangolin coronavirus and RaTG13 should also be able to use ACE2 as a receptor," Shi Zhengli said. "So what does the result of this molecular analysis tell us? Even this type of virus may use ACE2 (as a receptor). That said, they all have the potential to infect people across species. "

During the speech, Shi Zhengli mentioned that some of the slides she used were the same as those used in her public speech in 2018. One of the maps of China marked important hotspots in which SARS-like coronavirus may explode and overflow. They are mostly located in some provinces in southern and southwestern China. This is because her team detected SARS-like coronaviruses in bat populations in 11 provinces and cities in China. These viruses are divided into 4 evolutionary branches, and there are 2 evolutionary branches in Guangdong, Guangxi, and Yunnan. In addition, Shi Zhengli also found that in southern and southwestern China, the genetic diversity of bat-borne viruses is very large, and it has a good genetic material for cross-species infection.

"The bat-derived SARS-like coronavirus has popped out of both animals (referring to civet-SARS and camel-MERS), so will there be the next cross-infected coronavirus? My (then) guess Yes, this is a high probability event. But when, where, and which kind of coronavirus comes back, we don't know. At that time, my view was that we want to prevent the next SARS-like coronavirus cross-species infection. "She said "But I didn't expect it to happen at the end of 2019, just in the city where I live."

The covid outbreak has developed into a pandemic. The natural host of the new crown virus is considered to be probably a bat, but the intermediate host is still a mystery. Shi Zhengli said that the natural host of the virus has long been carrying viruses that are related to human viruses, and can be described as virus repositories. Several important natural hosts include bats, rodents, and wild birds. These natural hosts that carry the virus do not have the disease itself, and can hardly transmit the virus directly to humans, so they have to pass through intermediate hosts. During the traceability of SARS virus, they found that people who had close contact with the bats in the cave also showed signs of infection, but did not produce any clinical symptoms, but only detected antibodies to SARS-like coronavirus in humans. "This shows that there are opportunities for this bat to directly infect humans, but they are very rare and can be cleared by the human body." She said that there is still an intermediate host between the bat and the human, but no intermediate host has been found for covi.

Shi Zhengli introduced that the intermediary host must first have an ecological intersection with wild animals. It was accidentally infected with a virus carried by wild animals and caused a population epidemic. Then the virus can continue to spread and mutate in domestic animals. Then these intermediary hosts  must have close contact with people before the virus can transmit to other people. The genetic sequence identity of covi and the Yunnan chrysanthemum horseshoe bat coronavirus RaTG13 is as high as 96%, and the identity of the two coronavirus strains isolated from pangolins is 85% and 92%. "If a virus with 99% genetic homology and identity with covi is detected in a certain type of animal, we can determine that this host is an intermediate host for covi. Unfortunately, neither pangolin coronavirus nor bat coronavirus can infect humans across species within a short period of time, and then evolve to the extent of covi. So there must be an intermediary host. "

Finding intermediary hosts depends on molecular evidence. Shi Zhengli admits, "This time we haven't found any animals that have been eaten that are close to the virus (covi). We only found similar (bats) in the source wildlife, but only 96% of the nucleosides. Is it possible that pangolin is not an intermediate host, but a natural host? Which is the intermediary host? We have many speculations, but only molecular evidence can give a firm answer. Source tracing is for a long-term work. We must give scientists a certain amount of time and patience and let them look for intermediate hosts. "

A listener asked Shi Zhengli that the closure of the Wuhan Huanan Seafood Market, which is widely believed to be the source of the pandemic, has made it difficult to trace the source of the virus. Zhengli admits that the problem exists. When the SARS virus was traced back that year, Hong Kong scientists collected animal samples from the Guangdong market before the market closed, and soon found a virus with 99.7% homology to the SARS virus. This was the first time to find an intermediate host. The natural host was found by her team after 8 years. "The time it is impossible to collect samples of wild animals or wild animals in the market." She said that when this link was lost, there are two other ways of tracing the source of the virus. One is through the patient. "Patients engaged in wildlife trading. After the market is closed, where did the animals they traded go from? Where did their animals originally come from? We want to "Know the ins and outs"; the second is where the natural host exists, "For example, if we found a coronavirus closest to this virus in Yunnan, can we go to Yunnan and some neighboring countries to find it from bats and domesticated wildlife for clues?"

In Shi Zhengli's opinion, cross-species infection is not impossible to prevent. She introduced that coronavirus cross-species infections in humans need to cross two major barriers: the first barrier exists between wildlife and domestic animals; the second is between domestic animals and humans. If some barriers can be set up in these two links, it can be effectively prevented. "We now advocate 'One World One Health', and human health is actually based on the health of wild and domestic animals." She said that the current prevention measures focus on two aspects, The first is to prevent at the source of wild animals, eliminate wildlife consumption, and reduce damage to wild animals. It is best not to build various breeding farms in the habitats of wild animals and reduce the contact between domestic animals and wild animals. On the other hand, it is necessary to detect pathogens and perform a similar physical examination on viruses that exist in nature.

"We can pay a little price to proactively find the pathogen, assess the risk, give early warning, and move the barrier of prevention forward." Shi Zhengli said, "Humans have the ability to kill new infectious diseases transmitted by wildlife in the cradle.  The matter is not whether we can do it, but whether we do it or not. "

See also :

https://www.youtube.com/watch?v=_m_KCEBQv3s&t=147s

How China's "Bat Woman" Hunted Down Viruses from SARS to the New Coronavirus, Jane Qiu, The Scientific American,
https://www.scientificamerican.com/article/how-chinas-bat-woman-hunted-down-viruses-from-sars-to-the-new-coronavirus1/, 11 March 2020

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 Picture, copyright by : Gan Yung Chyan, KUCINTA SETIA