Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites

• DOI: 10.1073/pnas.0809524106
• Publication Date: 2009-03-25T02:29:06Z
• Authors: Sandrine Belouzard; Victor C. Chu; Gary R. Whittaker
• Keywords: Coronavirus; Cleavage (geology); spike protein; 2019-20 coronavirus outbreak

The coronavirus spike protein (S) plays a key role in the early steps of viral infection, with S1 domain responsible for receptor binding and S2 mediating membrane fusion. In some cases, S is proteolytically cleaved at S1-S2 boundary. case severe acute respiratory syndrome (SARS-CoV), it has been shown that virus entry requires endosomal protease cathepsin L; however, was also found infection SARS-CoV could be strongly induced by trypsin treatment. Overall, terms how cleavage might activate fusion, proteolytic processing remains unclear. Here, we identify site within (S2', R797). Mutation R797 specifically inhibited trypsin-dependent fusion both cell-cell pseudovirion assays. We introduced furin S2' 793-KPTKR-797 (S2'), as well junction S2. Introduction position allowed trypsin-independent which increased presence second position. Taken together, these data suggest novel priming mechanism protein, critical event on 797 acting concert to mediate infectivity.