Genetic study retraces the origins of coronaviruses in bats

Straits Times

13-05-2025

The new study's researchers argue that the Covid-19 pandemic got its start at the Huanan Seafood Market in Wuhan, China. PHOTO: PIXABAY
WASHINGTON - In the early 2000s, a coronavirus infecting bats jumped into raccoon dogs and other wild mammals in south-western China. Some of those animals were sold in markets, where the coronavirus jumped again, into humans.
The result was the severe acute respiratory syndrome (Sars) pandemic, which spread to 33 countries and claimed 774 lives. A few months into it, scientists discovered the coronavirus in mammals known as palm civets sold in a market at the centre of the outbreak.
In a study published last week, a team of researchers compared the evolutionary story of Sars with that of Covid-19 some 17 years later.
The researchers analysed the genomes of the two coronaviruses that caused the pandemics, along with 248 related coronaviruses in bats and other mammals.
Dr Jonathan Pekar, an evolutionary virus expert at the University of Edinburgh in Scotland and an author of the new study, said that the histories of the two coronaviruses followed parallel paths.
'In my mind, they are extraordinarily similar,' he said.
In both cases, Dr Pekar and his colleagues argue, a coronavirus jumped from bats to wild mammals in south-western China. In a short period of time, wildlife traders took the infected animals hundreds of miles to city markets, and the virus wreaked havoc in humans.
'When you sell wildlife in the heart of cities, you're going to have a pandemic every so often,' said Dr Michael Worobey, an evolutionary biologist at the University of Arizona and an author of the new study.
The study lands at a fraught political moment.
In April , the White House created a webpage called Lab Leak: The True Origin of Covid-19, asserting that the pandemic had been caused not by a market spillover but by an accident in a lab in Wuhan, China.
Earlier in May , in its proposed budget, the White House described the lab leak as 'confirmed' and justified an US$18 billion (S$23 billion) cut to the National Institutes of Health in part on what it described as the agency's 'inability to prove that its grants to the Wuhan Institute of Virology were not complicit in such a possible leak'.
The Chinese government responded with a flat denial that the pandemic had been caused by a Wuhan lab leak and raised the possibility that the virus had come instead from a biodefence lab in the United States.
'A thorough and in-depth investigation into the origins of the virus should be conducted in the US,' the statement read.
Dr Sergei Pond, a virus expert at Temple University, said that he did not consider the origin of Covid-19 settled. But he worried that the incendiary language from the two governments would make it difficult for scientists to investigate – and debate – the origin of Covid-19.
'If it wasn't tragic, you'd have to laugh; it's so farcical,' Dr Pond said.
In the first weeks of the Covid-19 pandemic in early 2020, claims circulated that the virus responsible was a biological weapon created by the Chinese army. A group of scientists who analysed the data available at the time rejected that idea.
Although they could not rule out an accidental lab leak, they favoured a natural origin of Covid-19.
As Dr Worobey and other scientists started studying the origin of Covid-19, US intelligence agencies were also assessing it. Their assessments have been mixed.
The FBI favoured an escape from the Wuhan Institute of Virology with moderate confidence; the CIA reached the same assessment, with only low confidence. The Energy Department leans with low confidence to the virus escaping from a different lab in Wuhan. Other agencies lean towards a natural origin.
The agencies have not made their evidence or their analyses public, so scientists cannot evaluate the basis of their conclusions.
However, Dr Worobey and other researchers have published a string of papers in scientific journals. Along the way, Dr Worobey became convinced that the Covid-19 pandemic had started at the Huanan Seafood Market in Wuhan.
'Scientifically, it's as clear as HIV or Spanish flu,' Dr Worobey said, referring to two diseases whose origins he has also studied.
For the new study, Dr Worobey, Dr Pekar and their colleagues compared the genomes of 250 coronaviruses, using their genetic similarities and differences to determine their relationships. They were able to reconstruct the history of the coronaviruses that cause both Sars and Covid-19 – known as Sars-CoV and Sars-CoV-2.
The ancestors of both viruses circulated in bats across much of China and neighbouring countries for hundreds of thousands of years. In the last 50 years or so, their direct ancestors infected bats that lived in south-western China and northern Laos.
As the coronaviruses infected the bats, they sometimes ended up inside a cell with another coronavirus. When the cell made new viruses, it accidentally created hybrids that carried genetic material from both of the original coronaviruses – a process known as recombination.
'These aren't ancient events,' said Dr David Rasmussen , a virus expert at North Carolina State University not involved in the new study. 'These things are happening all the time. These viruses are truly mosaics.'
In 2001, just a year before the Sars pandemic started in the city of Guangzhou, the researchers found, Sars-CoV underwent its last genetic mixing in bats.
Only after that last recombination could the virus have evolved into a human pathogen. And since Guangzhou is several hundred miles from the ancestral region of Sars-CoV, bats would not have been able to bring the virus to the city in so little time.
Instead, researchers generally agree, the ancestors of Sars-CoV infected wild mammals were later sold in markets around Guangzhou. A few months after the start of the Sars pandemic, researchers discovered Sars-CoV in palm civets and other wild mammals for sale in markets.
The researchers found a similar pattern when they turned to Sars-CoV-2, the cause of Covid-19. The last recombination in bats took place between 2012 and 2014, just five to seven years before the Covid-19 pandemic, several hundred miles to the north-east, in Wuhan.
That was also a substantial departure from the region where the virus' ancestors had circulated. But it was comparable to the journey that Sars-CoV took, courtesy of the wildlife trade.
Proponents of lab-leak theories have highlighted the long distance between Wuhan and the locations where the closest relatives of Sars-CoV-2 have been found. If bats could not fly to the region around Wuhan and infect wild mammals there, they maintain, then scientists must have collected the coronavirus from bats in south-west China and tinkered with it in their lab, from which it then escaped.
American scientists have criticised the Wuhan Institute of Virology for lax safeguards in their coronavirus experiments. But no one has offered evidence that the progenitor of Sars-CoV-2 was at the Wuhan Institute of Virology before the pandemic.
The new study by Dr Worobey and his colleagues shows that bat coronaviruses can travel long distances without the help of scientists, through the wildlife trade.
The researchers argue that these findings agree with studies that they published in 2022, which pointed to the Huanan Seafood Market in Wuhan as the place where the Covid-19 pandemic got its start.
Wild mammals were sold there, many early cases of Covid-19 were recorded there, and Chinese researchers collected different strains of Sars-CoV-2 carrying distinct mutations there.
Dr Worobey and his colleagues argued that the virus had twice spilled over from wild mammals at the market.
Dr Marc Eloit, the former director of the Pathogen Discovery Laboratory at Pasteur Institute in Paris, said that the new study was significant for providing a clear picture of where Sars-CoV-2 came from.
But he also observed that the coronavirus was markedly different from its closest known relatives in bats. After it split from those viruses, it must have mutated or undergone recombination to become well adapted for spreading in humans.
'I maintain that the possibility of a recombination event – whether accidental or deliberate – in a laboratory setting remains just as plausible as the hypothesis of emergence via an intermediate host on the market,' Dr Eloit said.
Dr Eloit and other scientists agreed that finding an intermediate form of Sars-CoV-2 in a wild mammal would make a compelling case for a natural spillover. Chinese authorities looked at some animals at the start of the pandemic and did not find the virus in them.
However, wildlife vendors at the Huanan market removed their animals from the stalls before scientists could study them. And once China put a stop to wildlife sales, farmers culled their animals.
'There's a big missing piece, and you really can't dance around it,' Dr Pond said. NYTIMES
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