Chances of Finding COVID-Causing Virus Ancestor ‘Almost Nil,’ Virologists Say

Chances of Finding COVID-Causing Virus Ancestor ‘Almost Nil,’ Virologists Say

The virus that causes COVID-19 probably shared an ancestor with bat coronaviruses more recently than scientists had thought. Researchers say it is unlikely that SARS-CoV-2 was the direct ancestor.

The full genomes of SARS CoV-2 and several closely related bat Coronaviruses suggest that they share a common ancestor many decades ago. The viruses swap RNA chunks with each other in a process called “recombination”. Each section has an evolutionary history. Scientists compared fragments from coronavirus genomes in the latest analysis, which was presented at the 7th World One Health Congress, Singapore, on 8 November. The analysis suggests that some sections of bat coronaviruses and SARS-CoV-2 shared a common ancestor as recently as 2016–just three years before the virus emerged in people in late 2019. The work was not peer reviewed.

Researchers believe that the time period between the ancestor SARS-CoV-2’s origin in bats and the virus’s leap to humans has been reduced. It doesn’t however explain how SARS CoV-2’s closest relative made this leap–a long-standing mystery surrounding the pandemic. Many scientists agree that it was likely an intermediary animal.

Direct ancestor

The study shows how difficult it will prove to be to locate the direct ancestor for SARS-CoV-2 bats due to how often coronaviruses combine and how long it has been. Edward Holmes, an evolutionary virusologist at the University of Sydney, Australia, says that there are very few chances of finding a direct ancestral. “That ship has sailed .”

Joel Wertheim, a molecular epidemiologist from the University of California San Diego, said that

SARS-2’s direct ancestor likely formed from multiple viruses and has been recombining with bats ever since. He says that although it is possible to identify viruses in bats for coronaviruses, it won’t reveal one direct ancestral parent.

Since the pandemic, many researchers in southeast Asia have been sequencing coronaviruses in bats and other mammals. In the hope of identifying the source of the pandemic virus, they have sequenced coronaviruses from older tissue samples kept in freezers. Scientists have not been able to identify a progenitor virus of SARS-CoV-2. This has led to speculation that the pandemic was caused by a virus that accidentally escaped the Wuhan Institute of Virology in the city that the pandemic began. The laboratory has also worked on coronaviruses.

Viral chunks

More than a dozen viruses that are closely related to SARS/CoV-2 have been identified from bats and pangolins. To determine their relationship to SARS-CoV-2, researchers often compare their entire genomes, which are about 30,000 nucleotides long. Using this method, they have found that SARS-CoV-2’s closest known relatives are a bat virus found in Laos called BANAL-52, whose genome is 96.8% identical to that of SARS-CoV-2, and a virus called RaTG13, found in Yunnan, southern China, which is 96.1% identical. The 3-4% difference between their genomes and that of SARS-CoV-2 suggests that there has been about 40-70 years of evolution since these viruses shared a common ancestor.

Researchers claim that comparing whole-genome sequences misses the importance of recombination for virus evolution. Some RNA fragments could be quite different from SARS/CoV-2, which suggests they are more distantly related. However, other fragments that are more similar suggest a closer relationship.

To account for recombination, the researchers compared 18 bat and pangolin viruses closely related to SARS-CoV-2, and spliced them into 27 segments. Spyros Lytras (an evolutionary virologist at Glasgow University, UK) presented the work in Singapore. Each segment, which is between a few hundred and a couple thousand nucleotide sequencings long, has a different evolutionary history. For each segment, the researchers used a larger subset of 167 related viruses to estimate how recently SARS-CoV-2 shared a common ancestor with a bat or animal virus. The work was described in a post on the virological.org discussion forum last month, and the co-authors plan on submitting it to a journal early next year.

Years, not decades

The analysis revealed that some segments had a common ancestor with SARS–CoV-2 only a few years back. Most of the fragments shared a common ancestor around 2007, but one small chunk, some 250 nucleotides long, could have shared a common ancestor in 2016, and another 550-nucleotide-long fragment in 2015–only 3-4 years before SARS-CoV-2 emerged in people. The earliest fragments were found in Yunnan, Laos and bats. Lytras says that the analysis suggests that southeast Asia and southern China are hotspots for SARS-CoV-2 ancestors due to the distance these viruses can travel with bat hosts.

” “It’s an intelligent approach,” Holmes says. “It gives you the purest signal of evolutionary time.” He points out, however, that some fragments were quite short, which makes those estimates less reliable because there are only a limited number of RNA nucleotides

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