SARS-CoV-2 Quasispecies Mediates Rapid Virus Evolution and Adaptation

We deep sequenced serially passaged SARS-CoV-2 to explore the potential and dynamics of the virus evolution. Alternate frequency and SNP data was used to mathematically model the mutation rate of SARS-CoV-2 under selective pressure of different cells lines. We demonstrate the presence of SARS-CoV-2 quasispecies that exhibits remarkable overall genome stability. However, the quasispecies nature of the virus population ensured rapid adaptation and mutation of the RRAR motif in spike proteins upon virus culture in Vero cells. Virus replication in TMPRSS2 competent cells led to a considerably higher reverse mutation rate, in addition to the emergence of novel envelope mutations.