A group from Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, etc. has reported that the 655Y mutation, present in the SARS-CoV-2 gamma and now omicron variants, is a key determinant of SARS-CoV-2 infection and transmission.
In order to evaluate the effect of H655Y mutation, five types of variants (MiA1, MiA2, NY7, NY13, and WA1-655Y) containing H655Y mutant, and two types of variants as controls (WA1 and NY6) not containing H655Y mutation were prepared．
Differences in replication and S processing of this panel of viruses were assessed by comparing growth in both Vero E6 and Vero-TMPRSS2 cells. More than 90% of the total S protein from these 655Y variants corresponded to the S2 cleaved form of the spike. In contrast, NY6 and WA1 controls showed poor cleavage efficiency.
In addition, human pneumocyte-like cells were infected with a representative panel of viruses containing the 655Y (NY7, NY13, WA1-655Y, NY6, and WA1) to assess viral growth and S protein processing. WA1-655Y demonstrated higher replication efficiency in our human airway epithelial system compared to WA1 wild type. Moreover, all isolates encoding the 655Y spike mutation exhibited enhanced spike cleavage. This demonstrates that the S:655Y polymorphism plays a crucial role in SARS-CoV-2 S protein processing and cell entry in human pneumocyte-like cells.
As a reference, it should be also noted that the spike mutations P681H in alpha variant and P681R harbored by kappa and delta variants are known to bring about enhanced Spike cleavage.