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CoronaVirus News Review In Brief: Michael Novakhov – SharedNewsLinks℠: Collection : COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv: Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion

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from Disease X-19 Medical Review from Michael_Novakhov (2 sites).

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.

Collection : COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv

Michael Novakhov – SharedNewsLinks℠

CoronaVirus News Review In Brief