RT Journal Article SR Electronic T1 Unique protein features of SARS-CoV-2 relative to other Sarbecoviruses JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.04.06.438675 DO 10.1101/2021.04.06.438675 A1 Matthew Cotten A1 David L. Robertson A1 My V.T. Phan YR 2021 UL http://biorxiv.org/content/early/2021/04/06/2021.04.06.438675.abstract AB Defining the unique protein features of SARS-CoV-2, the viral agent causing Coronavirus Disease 2019, may guide efforts to control this pathogen. We examined proteins encoded by the Sarbecoviruses closest to SARS-CoV-2 using profile Hidden Markov Model similarities to identify features unique to SARS-CoV-2. Consistent with previous reports, a small set of bat and pangolin-derived Sarbecoviruses show the greatest similarity to SARS-CoV-2. The analysis provided a measure of total proteome similarity and showed that a small subset of bat Sarbecoviruses are closely related but unlikely to be the direct source of SARS-CoV-2. Spike analysis reveals that the current SARS-CoV-2 variants of concern have sampled only 36% of the possible spikes changes which have occurred historically in Sarbecovirus evolution. It is likely that new SARS-CoV-2 variants with changes in these regions are compatible with virus replication and are to be expected in the coming months, unless global viral replication is severely reduced.Competing Interest StatementThe authors have declared no competing interest.