Identification of a common deletion in the spike protein of SARS-CoV-2

Two notable features have been identified in the SARS-CoV-2 genome: (1) the receptor binding domain of SARS-CoV-2; (2) a unique insertion of twelve nucleotide or four amino acids (PRRA) at the S1 and S2 boundary. For the first feature, the similar RBD identified in SARs-like viruses from pangolin suggests that the RBD in SARS-CoV-2 may already exist in animal host(s) before it transmitted into humans. The remaining puzzle is the history and function of the insertion at S1/S2 boundary, which is uniquely identified in SARS-CoV-2.

In this study, we identified two variants from the first Guangdong SARS-CoV-2 cell strain, with deletion mutations at the polybasic cleavage site (PRRAR) and its flank sites. More extensive screening indicates the deletion at the flank sites of PRRAR could be detected in 3 of 68 clinical samples and half of 22 in vitro-isolated viral strains.

These data indicate (1) the deletion of QTQTN, at the flank of the polybasic cleavage site, is likely to benefit SARS-CoV-2 replication or infection in vitro, but is under strong purification selection in vivo since it is rarely identified in clinical samples; (2) there could be a very efficient mechanism for deleting this region from the viral genome as the variants losing 23585-23599 are commonly detected after two rounds of cell passage. The mechanistic explanation for this in vitro adaptation and in vivo purification processes (or reverse) that led to such genomic changes in SARS-CoV-2 requires further work to determine. Nonetheless, this study has provided valuable clues to aid further investigation of spike protein function and virus evolution. The deletion mutation identified by in vitro isolation should also be noted for current vaccine development.