SARS-CoV-2, a novel coronavirus (CoV) producing worldwide pandemic 1 , has a furin cleavage site (PRRAR) in its spike protein that is absent in other group 2B CoVs 2 . To explore whether the furin cleavage site contributes to infection and pathogenesis, we generated a mutant SARS-CoV-2 deleting the furin cleavage site (ΔPRRA). SARS-CoV-2 ΔPRRA replicates with faster kinetics, has improved fitness in Vero E6 cells, and has reduced spike protein processing as compared to parental SARS-CoV-2. However, the ΔPRRA mutant has reduced replication in a human respiratory cell line and was attenuated in both hamster and K18-hACE2 transgenic mouse models of SARS-CoV-2 pathogenesis. Despite reduced disease, the ΔPRRA mutant conferred protection against rechallenge with the parental SARS-CoV-2. Importantly, COVID-19 patient sera and receptor-binding domain (RBD) monoclonal antibodies had lower neutralization values against the ΔPRRA mutant versus parental SARS-CoV-2 likely due to increased particle/PFU ratio. Together, these results demonstrate a critical role for the furin cleavage site in SARS-CoV-2 infection and highlight the importance of this site in evaluating antibody neutralization activity.
【저자키워드】 COVID-19, SARS-CoV-2, coronavirus, spike, 2019-nCoV, furin-cleavage,