Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic

Maciej F Boni; Philippe Lemey; Xiaowei Jiang; Tommy Tsan-Yuk Lam; Blair Perry; Todd Castoe; Andrew Rambaut; David L Robertson

It is clear from our analysis that viruses closely related to SARS-CoV-2 have been circulating in horseshoe bats for many decades. The substantial unsampled diversity on the SARS-CoV-2/RaTG13 lineage suggests that there is a major clade of bat sarbecoviruses with generalist properties -with respect to their ability to infect a range of mammalian cells -that facilitated its jump to humans and may do so again. Although the human ACE2-compatible receptor binding domain was very likely to have been present in a bat sarbecovirus lineage that ultimately lead to SARS-CoV-2, this RBD sequence has thus far only been found in a few pangolin viruses. Furthermore, the other key feature thought to be instrumental to SARS-CoV-2's ability to infect humans -a polybasic cleavage site insertion in the Spike protein -has been seen in another close bat relative of the SARS-CoV-2 virus ; however, the sequence is different and it is likely an independent event.