RT Journal Article
SR Electronic
T1 Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.13.243303
DO 10.1101/2020.08.13.243303
A1 Guido Papa
A1 Donna L. Mallery
A1 Anna Albecka
A1 Lawrence Welch
A1 Jérôme Cattin-Ortolá
A1 Jakub Luptak
A1 David Paul
A1 Harvey T. McMahon
A1 Ian G. Goodfellow
A1 Andrew Carter
A1 Sean Munro
A1 Leo C. James
YR 2020
UL http://biorxiv.org/content/early/2020/08/19/2020.08.13.243303.abstract
AB Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells by binding to the host cell receptor Ace2 and undergoing virus-host membrane fusion. Fusion is triggered by the protease TMPRSS2, which processes the viral Spike (S) protein to reveal the fusion peptide. SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin in order to prime S protein for TMPRSS2 processing. Here we show that CRISPR-Cas9 knockout of furin reduces, but does not prevent, the production of infectious SARS-CoV-2 virus. Comparing S processing in furin knockout cells to multibasic site mutants reveals that while loss of furin substantially reduces S1-S2 cleavage it does not prevent it. SARS-CoV-2 S protein also mediates cell-cell fusion, potentially allowing virus to spread virion-independently. We show that loss of furin in either donor or acceptor cells reduces, but does not prevent, TMPRSS2-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation. Our results show that while furin promotes both SARS-CoV-2 infectivity and cell-cell spread it is not essential, suggesting furin inhibitors will not prevent viral spread.Competing Interest StatementThe authors have declared no competing interest.