The origin of SARS-CoV-2

The fact that severe acute respiratory syndrome coronavirus 2 derived from bat coronaviruses highlights inherent issues of the way we interact with the environment. Talha Burki reports.

Researchers examining coronaviruses and bats are used to working with large numbers. A 2017 study of 12 333 bats from Latin America, Africa, and Asia found that almost 9% carried at least one of 91 distinct coronaviruses. The authors estimated that there are at least 3200 coronaviruses that infect bats. Moreover, there are over 1400 species of bat. Figuring out which ones are susceptible to which coronaviruses is no small task. Bats are incredibly varied and successful creatures. In evolutionary terms, fruit-eating bats diverged from insect-eating bats some 50 million years ago.

The picture becomes even more complicated when we start to consider which bat viruses are likely to pose a threat to human beings. “Going after bats will only give you partial information—the viruses you are looking at may or may not get the additional mutations they need to be transmissible among humans”, explains Stanley Perlman, professor of microbiology and immunology at the University of Iowa, IA, USA. “There has almost always been an intermediary involved, and without knowing what that is and what changes the virus would have to undergo, it is very hard to make any kind of predictions.”

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The story of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a case in point. A paper published in July, 2020, traced the origins of SARS-CoV-2. The researchers concluded that it came from a virus with relatively generalist properties circulating in horseshoe bats. “Everything points to a bat sarbecovirus reservoir; we are very confident about this”, said David Robertson, head of bioinformatics at the Medical Research Council–University of Glasgow Centre for Virus Research, Scotland, UK, and co-author of the paper. The evolutionary analysis suggested that the lineage from which SARS-CoV-2 emerged has been present in bats for several decades.

“The generalist property of the virus means an intermediate host is not required for any evolutionary change”, said Robertson. “As the virus has been around for decades it may have emerged in another host and this could be the missing intermediate species but we are inferring that this would only facilitate transmission.” The fact that SARS-CoV-2 was first detected in Wuhan, China, far from where the horseshoe bat is found, hints at the presence of an intermediary.

Some have posited that the pangolin could be this missing link. Pangolins have reportedly fallen sick as a result of coronavirus infection, which would mean they are not a natural reservoir. But that leaves the possibility that the pangolin is facilitating transmission to humans. SARS-CoV-2 can jump to other animals such ferrets and cats. “The virus would not need to evolve in the pangolin, it would just need to be brought into contact with humans”, explains Robertson. And it is still too soon to rule out direct bat–human transmission.

Still, there is one theory that can be dismissed. From the earliest days of the pandemic, there has been speculation that the new virus had escaped, or even been deliberately released, from the Wuhan Institute of Virology. At a White House press conference on May 1, 2020, US President Donald Trump declined to assert that SARS-CoV-2 had occurred naturally. When asked what gave him a “high degree of confidence that this [virus] originated from the Wuhan Institute of Virology”, Trump replied “I can’t tell you that. I’m not allowed to tell you that.”

“If the virus had been human-made, that would show in its genome”, counters Robertson. “Besides, if you were going to create a coronavirus that can be transmitted by humans, you would almost certainly start with the first SARS virus. SARS-CoV-2 is like nothing we have seen before. It really is highly unlikely that someone created it; it is not put together from pieces we know about.” SARS-CoV-2 is closely related to other beta coronaviruses such as RaTG13, a bat virus that the Wuhan Institute of Virology has been working on. But it only shares 96% of its genome sequence with RaTG13, which makes them roughly as similar as human beings and chimpanzees, and points to a common ancestor rather than one springing from the other.

The plethora of bat coronaviruses, coupled with the uncertainty about the role of an intermediary animal, makes it tricky to know how to go about preventing a future spillover. Live animal markets are an obvious risk for the emergence and spread of zoonotic diseases, but they are part of the culture of south east Asia. “Certainly having a society which did not have such an interface with animals would be helpful, but I am not at all convinced that we should be telling chunks of the world that they should not be buying live animals”, said Perlman.

The argument against insisting that indigenous peoples discontinue consuming bush meat is also strong. “There are tens of millions of tribal people around the world who do not farm; they get their animal protein through hunting”, points out James Wood, head of the Department of Veterinary Medicine at the University of Cambridge, UK. “We have to make sure they can continue living the way they always have. Stopping them from eating bush meat would be downright dangerous and unlikely to succeed”. Eliminating markets for live, wild exotic animals is a different matter entirely. That would at least minimise intense contact between different species. Perlman believes the Chinese government will eventually prove amenable to such a measure.

There is evidence that preserving natural habitats reduces the risk of diseases spilling over from wildlife. In early August, a paper published in Nature found that ecosystems that were heavily used by human beings contained a greater abundance and wider variety of wildlife that carried pathogens and parasites capable of infecting people. “We need to look at the parts of the world where spillover is common and think about the effect that environmental degradation may be having”, notes Wood. “It seems that wildlife species that are under environmental stress, often due to land-use change, are more likely to excrete large doses of virus; that raises the risk of both an epidemic in the host population and of spillover.”

“The major thing is to change our behaviour”, adds David Morens, senior advisor to the director at the US National Institute of Allergy and Infectious Diseases. “That means stopping deforestation, perturbing the environment, bat cave tourism, and intensive farming.” Prompt detection of new viruses is also crucial. But the places where new zoonotic diseases tend to emerge do not typically have strong public health surveillance systems. “We have to invest in infrastructure that would allow outbreaks to be detected far earlier than they currently are”, Wood says.

None of these measures can be meaningfully enacted without cross-country collaboration. Morens advocates strengthening international bodies such as WHO and the International Red Cross, as well as incorporating applied research into the international agenda. “There is this entire universe of micro-organisms and viruses out there and we probably know 1–2% of it; we need to find out where these pathogens are and catalogue them and study them”, he explained. “We need scientists from all over the world to work out what the priorities are and how we can fund them.” The sooner all this can happen, the better. If there is one lesson from COVID-19, it is that a pandemic virus is just a few mutations away.

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