Significant role of host sialylated glycans in the infection and spread of severe acute respiratory syndrome coronavirus 2

SARS-CoV-2, which has been highly transmissible and rapidly spreading worldwide, has caused approximately 458 million confirmed cases of COVID-19 with more than 6 million deaths by March 2022. Here we found that SARS-CoV-2 infection was significantly inhibited by α2-6-linked sialic acid-containing compounds and by depletion of cell surface sialic acid with only a minor effect on SARS-CoV infection. We identified that SARS-CoV-2 spike S1 subunit directly binds to α2-6-linked sialoglycans for efficient attachment to host cell surface. Our finding indicated that host sialoglycans play a significant role in the efficient infection of SARS-CoV-2, which provides a novel understanding of the molecular basis explaining the rapid spread of SARS-CoV-2 over SARS-CoV.