PT  - JOURNAL ARTICLE
AU  - Guido Papa
AU  - Donna L. Mallery
AU  - Anna Albecka
AU  - Lawrence Welch
AU  - Jérôme Cattin-Ortolá
AU  - Jakub Luptak
AU  - David Paul
AU  - Harvey T. McMahon
AU  - Ian G. Goodfellow
AU  - Andrew Carter
AU  - Sean Munro
AU  - Leo C. James
TI  - Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion
AID  - 10.1101/2020.08.13.243303
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.08.13.243303
4099  - http://biorxiv.org/content/early/2020/08/19/2020.08.13.243303.short
4100  - http://biorxiv.org/content/early/2020/08/19/2020.08.13.243303.full
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.