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Virology: Dating SARS-CoV-2 divergence from bat viruses

Nature Microbiology

July 28, 2020

SARS-CoV-2 is likely to have diverged from the most closely related bat viruses approximately 40–70 years ago, reports a paper in Nature Microbiology. The findings suggest that the lineage giving rise to SARS-CoV-2 may have been circulating in bats for decades.

Understanding the evolutionary history of SARS-CoV-2 has been difficult because coronaviruses are known to recombine (exchange genetic material between different viruses) and small genomic subregions of the virus may have different ancestries. The bat virus RaTG13 has been identified as the most closely related virus to SARS-CoV-2, suggesting that a bat origin for the COVID-19 outbreak is likely. However, research has also identified similar coronaviruses in pangolins (notably, a pangolin virus sampled in Guangdong in 2019; Pangolin-2019) and it has been proposed that they may have been an intermediary host.

Maciej Boni and colleagues analysed the evolutionary history of SARS-CoV-2 using genomic data on sarbecoviruses (the subgenus to which SARS-CoV-2 belongs). They employed three approaches to identify regions in the virus that had not undergone recombination and that could be used to reconstruct its evolution. The approaches all suggest that RaTG13 and SARS-CoV-2 share a single ancestral lineage and estimate that SARS-CoV-2 genetically diverged from related bat sarbecoviruses in 1948, 1969 and 1982, respectively. The authors also examined the receptor-binding domain (RBD) of the virus spike protein, which enables it to use the human ACE2 receptor to enter cells. Although this has been shown to be genetically more similar to pangolin viruses than RaTG13, the authors found that the spike protein did not show evidence of recombination taking place between the lineage leading to SARS-CoV-2 and other known sarbecoviruses. Based on this finding, they propose this protein and its RBD are an ancestral trait of the lineage leading to SARS-CoV-2, RaTG13 and Pangolin-2019. The authors conclude that although SARS-CoV-2 and pangolin viruses share a common ancestor, and although pangolins may have played a role in the transmission to humans, they are unlikely to be an intermediate host for the virus.

The authors argue that the long divergence period of SARS-CoV-2 indicates there may be unsampled virus lineages in bats that may have zoonotic potential due to the ancestral position of human-adapted contact residues on the SARS-CoV-2 RBD, but state that better sampling is needed to assess this. They conclude that existing diversity and the dynamic process of recombination amongst lineages in the bat reservoir demonstrate how difficult it will be to identify viruses with the potential to cause significant human outbreaks before they emerge, underscoring the need for real-time human disease surveillance systems that can rapidly identify and classify pathogens.

doi: 10.1038/s41564-020-0771-4

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