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Possible Bat Origin of Severe Acute Respiratory Syndrome Coronavirus 2

CDC-Emerging Infection Diseases
Volume 26, Number 7—July 2020 (Preliminary Release)


Although the Wuhan market was initially suspected to be the epicenter of the epidemic, the immediate source remains elusive. The close relatedness among SARS-CoV-2 strains suggested that the Wuhan outbreak probably originated from a point source with subsequent human-to-human transmission, in contrast to the polyphyletic origin of Middle East respiratory syndrome coronavirus (14). If the Wuhan market was the source, a possibility is that bats carrying the parental SARSr-BatCoVs were mixed in the market, enabling virus recombination. However, no animal samples from the market were reported to be positive. Moreover, the first identified case-patient and other early case-patients had not visited the market (15), suggesting the possibility of an alternative source.

Because the RBD is considered a hot spot for construction of recombinant CoVs for receptor and viral replication studies, the evolutionarily distinct SARS-CoV-2 RBD and the unique insertion of S1/S2 cleavage site among Sarbecovirus species have raised the suspicion of an artificial recombinant virus. However, there is currently no evidence showing that SARS-CoV-2 is an artificial recombinant, which theoretically might not carry signature sequences. Further surveillance studies in bats are needed to identify the possible source and evolutionary path of SARS-CoV-2.


(Credit to DUer JCMach1 for originally posting about this article.)




By March, the wild-virus theory was still the most likely explanation of the origin of SARS-CoV-2--but it was starting to look a little ragged around the edges. For one thing, the Wuhan Institute of Virology, not far from the animal markets in downtown Wuhan, houses the world's largest collection of coronaviruses from wild bats, including at least one virus that bears a resemblance to SARS-CoV-2. What's more, Wuhan Institute of Virology scientists have for the past five years been engaged in so-called "gain of function" (GOF) research, which is designed to enhance certain properties of viruses for the purpose of anticipating future pandemics. Gain-of-function techniques have been used to turn viruses into human pathogens capable of causing a global pandemic.

This is no nefarious secret program in an underground military bunker. The Wuhan lab received funding, mostly for virus discovery, in part from a ten-year, $200 million international program called PREDICT, funded by the U.S. Agency for International Development and other countries. Similar work, funded in part by the U.S. National Institutes of Health, has been carried out in dozens of labs throughout the world. Some of this research involves taking deadly viruses and enhancing their ability to spread quickly through a population—research that took place over the objections of hundreds of scientists, who have warned for years of the program's potential to cause a pandemic.


The answer that Fouchier came up with was a technique known as "animal passage," in which he mutated the bird-flu virus by passing it through animals rather than cell cultures. He chose ferrets because they were widely known as a good stand-in for humans—if a virus can jump between ferrets, it is likely also to be able to jump between humans. He would infect one ferret with a bird-flu virus, wait until it got sick, and then remove a sample of the virus that had replicated in the ferret's body with a swab. As the virus multiplies in the body, it mutates slightly, so the virus that came out of the ferret was slightly different from the one that went into it. Fouchier then proceeded to play a version of telephone: he would take the virus from the first ferret and infect a second, then take the mutated virus from the second ferret and infect a third, and so on.


What followed was a fierce debate among scientists over the risks versus benefits of the gain-of-function research. Fouchier's work, wrote Harvard epidemiologist Marc Lipsitch in the journal Nature in 2015, "entails a unique risk that a laboratory accident could spark a pandemic, killing millions."


The NIH eventually came down on the side of Fouchier and the other proponents. It considered gain-of-function research worth the risk it entailed because it enables scientists to prepare anti-viral medications that could be useful if and when a pandemic occurred.


A virus produced with animal passage methods would be much harder to spot. These viruses are not directly manipulated. When the virus passes from one animal to the next, it undergoes something similar to what would happen in the wild during the course of its evolution.

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