SARS-CoV-2 originated from SARS-CoV-1-related Bat-CoVs through Pan-CoVs rather than from SARS-CoV-2-related Bat-CoVs

Abstract

The emergence of the novel SARS-CoV-2 in 2019 sparked a dispute concerning its origin. Here, we report that the SARS-CoV-2 originated through pangolin-coronavirus (Pan-CoVs) from the SARS-CoV-related-bat-coronaviruses (SARS-CoV-1-rB-CoVs) rather than from SARS-CoV-2-related-bat-coronaviruses (SARS-CoV-2-rB-CoVs), in contrast to the previous thought. Further, our analyses strongly suggest that the Pan-CoVs evolved from the SARS-CoV-1-rB-CoVs without recombination. Further, our results suggest that the SARS-CoV-1-rB-CoVs' perhaps jumped into the pangolin, which forced the viruses to mutate and adapt to the new host, and resulted in the origin of Pan-CoVs. Surprisingly, the Pan-CoVs formed an evolutionary intermediate between SARS-CoV-2 and SARS-CoV-2-rB-CoVs at the spike gene. Our findings also suggest that the Pan-CoV/GX and Pan-CoV/Guangdong lineages recombined to form the SARS-CoV-2 spike gene. We also found evidence that the SARS-CoV-2-rB-CoVs spike gene evolved via recombination between Pan-CoV/Guangdong and SARS-CoV-1-rB-CoVs. Overall, our findings suggest that the SARS-CoV-2 emerged from SARS-CoV-1-rB-CoVs through host jumping.