Questions concerning the proximal origin of SARS‐CoV‐2

tropism/adaptation, resistance to neutralizing antibodies, or immune evasion. 2 Interestingly, clinical SARS-CoV-2 isolates to date have only a single high-frequency nonsynonymous mutation, D614G, in their S protein.9 Based on currently known mutation rates and patterns in clinical isolates of SARS-CoV-2, the S protein does not appear to be a mutational "hot spot" for SARS-CoV-2, unlike other human CoVs.SARS-CoV-2 is the seventh HCoV, but the first HCoV with pandemic potential.SARS-CoV disappeared without a pandemic, and MERS-CoV is mostly endemic to the Arabian Peninsula with some additional limited traveler infections resulting in outbreaks in South Korea.3,4 These unique features of SARS-CoV-2 raise several questions concerning the proximal origin of the virus that require further discussion.