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SARS-CoV-2 Lineage May Go Back 'Decades' in Bats, Phylogenetic Analysis Suggests

NEW YORK – Based on several independent phylogenetic analyses, researchers from the US, Belgium, China, and the UK have traced the evolutionary history of the SARS-CoV and SARS-CoV-2 viruses — members of a sub-genus of coronaviruses dubbed sarbecoviruses — back several decades in bats.

For a paper published in Nature Microbiology on Tuesday, the team attempted to tease out the history of sarbecoviruses such as SARS-CoV-2 with the help of already available whole-genome sequences of dozens of SARS-CoV isolates from humans and animals going back to 2003 and 2004, along with sequences from MERS-CoV and other coronaviruses isolated from humans and animals. Aligning these genomes highlighted rampant recombination across such coronaviruses, though SARS-CoV-2 did not appear to stem from clear recombination events involving other known viruses.

"The existing diversity and dynamic process of recombination amongst lineages in the bat reservoir demonstrate how difficult it will be to identify viruses with potential to cause major human outbreaks before they emerge," co-first authors Maciej Boni, a researcher at Penn State's Center for Infectious Disease Dynamics, and Philippe Lemey, a microbiology, immunology, and transplantation researcher at KU Leuven in Belgium, and their colleagues wrote.

Moreover, they suggested, the study "underscores the need for a global network of real-time human disease surveillance systems … with the capacity to rapidly deploy genomic tools and functional studies for pathogen identification and characterization."

Using independent phylogenetic analyses that took the recombination events into account, the researchers searched for the last shared ancestor between SARS-CoV-2 and a bat coronavirus known as RaTG13, which has roughly 96 percent genome sequence identity with it. From these and other analyses, they estimated that the lineage leading to SARS-CoV-2 split from other sarbecoviruses circulating in bats as far back as 1948 and as recently as 1982.

In contrast, the team saw signs that a lineage containing the SARS-CoV-2 and RaTG13 viruses likely split off from the lineage containing viruses found in pangolins as far back as the 1800s, which argues against a role for pangolins as an intermediate host during the jump into humans.

"It is clear from our analysis that viruses closely related to the SARS-CoV-2 have been circulating in horseshoe bats for many decades," the authors wrote. "The unsampled diversity descended from the SARS-CoV-2/RaTG13 common ancestor forms a clade of bat sarbecoviruses with generalist properties — with respect to their ability to infect a range of mammalian cells — that facilitate its jump to humans and may do so again," they suggested.

Past studies have highlighted genetic similarities between coronaviruses detected in bats or pangolins and the SARS-CoV-2 virus that began causing COVID-19 disease in China's Hubei province in late 2019, the team explained. Even so, gaps remain in the evolutionary history of SARS-CoV-2, and there is more to learn about when and how the virus made the leap from an animal reservoir or intermediate host into humans.

"If stopping an outbreak in its early stages is not possible — as was the case for the COVID-19 epidemic in Hubei — identification of origins and point sources is nevertheless important for containment purposes in other provinces and prevention of future outbreaks," the authors wrote.