Recombination and lineage-specific mutations led to the emergence of SARS-CoV-2

Juan Angel Patino-Galindo; Ioan Filip; Mohammed AlQuraishi; Raul Rabadan

In the three months since the initial reports in mid-December 2019, the recent COVID-19 pandemic has caused close to 10,000 fatalities associated with severe respiratory disease worldwide 1 . The causative agent of COVID-19 was identified as a previously unknown RNA coronavirus (CoV) virus, dubbed SARS-CoV-2, of the betacoronavirus genus 2 , with 80% similarity at nucleotide level to the Severe Acute Respiratory Syndrome (SARS) coronavirus 3 . SARS-CoV and SARS-CoV-2 are the only members of Sarbecovirus subgenus of betacoronavirus that are known to infect humans. Other members of this subgenus are frequently found in bats, hypothesized to be the natural reservoir of many zoonotic coronaviruses 4 . In January 2020, a Rhinolophus affinis bat isolate obtained in 2013 from the Yunnan Province in China (named RaTG13) was reported to have 96% similarity to SARS-CoV-2 5 , suggesting that the ancestors of the outbreak virus were recently circulating in bats. However, the specific molecular and evolutionary determinants that enable a virus like the recent ancestor of SARS-CoV-2 to jump species remain poorly characterized.