Explained: Probing the origin of SARS-CoV-2 virus

The WHO fact-finding team had initially rejected the possibility of a lab-leak saying it is “extremely unlikely” and that further investigation into it was not required. However, at a press briefing on February 12, the WHO Chief Tedros A Ghebreyesus appeared to backpaddle saying that on discussing with a few team members “all hypotheses [including the lab-leak] remain open and require further analysis and studies”.

After several months of delay, concerns over access and bickering between China and the U.S., a 17-member team from the World Health Organization began the field visit on January 29, 2021 to unearth the origin of SARS-CoV-2 virus that has so far spread to 108 million people and killed nearly 2.4 million people across the globe.

As per WHO, the field visits included the Wuhan Institute of Virology, Huanan market, Wuhan CDC (Center for Disease Control and Prevention) laboratory. According to WHO, the team was “limited by visits organised by Chinese hosts and had no contact with community members, because of health restrictions”, Reuters reported

What are the four scenarios of virus origin that were investigated?  

The WHO team undertook scientific investigations to look at four main scenarios for the origin of the virus. The first possibility is that a single individual had got infected with the virus through direct contact with bats and then spread it to others before the virus made its way to Wuhan. The second scenario is of the virus crossing the species barrier from bats to humans through an intermediary species, which has still not been found. The third possibility is that the virus originated outside China and spread to Wuhan through imported frozen food; and the last scenario is the virus leaked from the Wuhan Institute of Virology, which has been studying coronaviruses.  

When and where did the outbreak begin in China?

Though the first cluster of cases was reported from Wuhan in December, early data suggest that the virus could have been circulating in the Chinese city for several weeks before it was identified. According to the WHO, there have not been any large-scale outbreaks in the Chinese city or outside before December 2019. But the team has not ruled out the possibility of the virus circulating in other regions well before December 2019. 

What role did the Huanan wet market play in the outbreak?

Though the first cluster of cases reported in Wuhan had links to the wet market, it soon became apparent that several infected people did not have any link to it. Though there is not enough evidence to determine how the virus entered the wet market, there are two likely possibilities — either the virus was introduced into the market through one or more infected people or was introduced through frozen food. 

Has the possibility of a lab-leak been ruled out?

The WHO fact-finding team had initially rejected the possibility of a lab-leak saying it is “extremely unlikely” and that further investigation into it was not required. However, at a press briefing on February 12, the WHO Chief Tedros A Ghebreyesus appeared to backpaddle saying that on discussing with a few team members “all hypotheses [including the lab-leak] remain open and require further analysis and studies”.

In a tweet, Dr. Michael Eisen, Professor of genetics, genomics and development at the University of California, Berkeley, says: “There is an at least plausible case for lab accident too, in that the virus first appeared in the rough vicinity of a lab that is studying precisely this kind of virus and doing the kind of experiments that, if something went wrong, would lead to disaster. That said, we have to be extremely careful about interpreting the circumstantial evidence relating to the Wuhan virus lab.”

Did the virus directly jump from bats to humans? 

Investigation by the WHO team strongly suggests that though bats were the reservoirs of the virus, it is unlikely that the virus jumped directly from bats to humans. The virus may have crossed from bats to another animal species and finally to humans. The direct spillover of the virus from bats to humans is unlikely as Wuhan is miles away from any natural bat habitat. The team has not been able to find the intermediary host.  

The role of an intermediary host gains currency as previous coronavirus outbreaks — SARS and MERS —have been through civets and camels, respectively. The SARS-CoV-2 virus with its distinctive spike protein that allows it to bind to human receptors and enter cells would have either evolved in the intermediate host itself making the virus readily spread from one person to another or would have gained the ability for human-to-human transmission in humans after jumping from an intermediate host. In the latter case, the virus would have evolved certain characteristics in the intermediate host and then gained other features within a human host. The virus would have been silently spreading in humans in a limited fashion before gaining the ability to cause a large outbreak and then the pandemic. 

What do the genome sequence data reveal about the virus origin?  

Based on analysis of public genome sequence data from SARS-CoV-2 and related viruses, scientists have not found any evidence that the virus was made in a laboratory or engineered by humans.  

The receptor binding domain (RBD) in SARS-CoV-2 has been found to have a high affinity to the human ACE2 receptor. Though the RBD seen in SARS-CoV-2 virus had not been previously observed in nature, scientists soon found a similar receptor binding domain in coronaviruses isolated from pangolins. This is the reason why some scientists think pangolins could have been an intermediate host. 

Similarly, the cleavage site on SARS-CoV-2, which allows the virus to enter human cells, while being novel among SARS-like coronaviruses, has been found all across the coronavirus family, including the feline coronaviruses. Similar to the SARS-CoV-2 RBD, the polybasic cleavage site is therefore a common feature observed during the evolution of coronaviruses, a letter published in Nature Medicine says.

Dr. David Robertson, Professor, Viral Genomics and Bioinformatics at MRC-University of Glasgow Centre for Virus Research, in an email says based on genome sequence data there are no signatures of the virus being altered or manipulated in a lab. “Although showing differences in sequence similarity, SARS-CoV-2 looks very much like a natural virus transferred from the same horseshoe bat species as the first SARS (severe acute respiratory syndrome) virus, and is now evolving as would be expected in the human population,” Dr. Robertson says. 

According to him, there is resounding proof that the virus has not been engineered in a lab. “First, if one was to engineer a SARS-like virus you would copy SARS-CoV-1 more closely. This new virus is highly divergent to SARS-CoV-1. There are lots of these viruses in bats and evidence that some could use human cells. So the emergence of this new virus isn’t all that surprising,” emphasises Dr. Robertson. He also says genome sequencing would detect any genetic changes made to the virus.  

Dr Koen Van Rompay from the California National Primate Research Center, University of California, in an email says: “Our understanding of how to manipulate certain gene sequences to change in vivo virulence and pathogenesis is still very limited, and would be mostly trial and error. It would be very difficult to predict the outcome especially when introducing multiple mutations that can interact with each other.” Dr. Rompay adds: “When viruses replicate in vivo and transmit, that is the most efficient way to get selection for more replication-competent mutants that can continue to evolve.” 

Published in The Hindu on February 14, 2021

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