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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agentof coronavirus disease 19 (COVID-19) has rapidly spread to the entire world within a few months. The origin of SARS-CoV-2 has been related to the lineage B Betacoronavirus
SARS-CoV and SARS-related coronaviruses found in bats. Early characterizations of the SARS-CoV-2 genome revealed the existence of a distinct 4 amino acid insert within the spike (S) protein (underlined, SPRRAR↓S), at the S1/S2 site located at the interface between the S1 receptor binding subunit and the S2 fusion subunit...
We provide direct biochemical evidence that the site S1/S2 is recognized and cleaved by furin. However, other proteases such as PC1 another member of the PC family of proteases, trypsin-like proteases, and cathepsins can all efficiently recognize and cleave SARS-CoV-2 S1/S2 cleavage site. These data confirm earlier findings showing the SARS-CoV-2 entry was dependen at least in part, on lysosomal cathepsins and the cell surface-expressed TTSPs such as TMPRSS2.
Overall, the novel S1/S2 insert is likely to enhance spike protein cleavage by multiple proteases beyond that other SARS-like viruses (e.g. containing the sequence SR↓S). The role of the fusion peptide-proximal S2’ site remains to be evaluated, but its sequence (PDPSKPSKR↓SFIEDLLF) is not distinctly different from other SARS-like viruses.
Original Study Published in IScience:
