Abstract
SARS-CoV-2, a novel coronavirus (CoV) producing worldwide pandemic1
, 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