Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-a new coronavirus that has led to a worldwide pandemic¹-has a furin cleavage site (PRRAR) in its spike protein that is absent in other group-2B coronaviruses². To explore whether the furin cleavage site contributes to infection and pathogenesis in this virus, we generated a mutant SARS-CoV-2 that lacks the furin cleavage site (ΔPRRA). Here we report that replicates of ΔPRRA SARS-CoV-2 had faster kinetics, improved fitness in Vero E6 cells and reduced spike protein processing, as compared to parental SARS-CoV-2. However, the ΔPRRA mutant had 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

SUBMITTER: Johnson BA 

PROVIDER: S-EPMC8175039 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature