Evolutionary dynamics of heparan sulfate utilization by SARS-CoV-2.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants have acquired enhanced infectivity compared to earlier variants. To elucidate the underlying molecular mechanisms, we conducted CRISPR library screening to identify cell surface molecules that interact with the Omicron spike protein. Our findings revealed a significantly higher affinity between the Omicron spike and cell surface heparan sulfate compared to the wild-type spike. This increased binding affinity enables Omicron variants to infect cells expressing low levels of ACE2, which are minimally infected by the wild-type virus. Mutational analysis of heparan sulfate binding sites on the Omicron spike protein, coupled with electrostatic potential mapping, suggested that the accumulation of positively charged mu

SUBMITTER: Higuchi S 

PROVIDER: S-EPMC12345153 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature