About: Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion

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About: Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion
Creator	Goodfellow, Ian Papa, Guido Paul, David Albecka, Anna Munro, Sean James, Leo Carter, Andrew Luptak, Jakub Mallery, Donna Cattin-Ortolá, Jérôme Mcmahon, Harvey Welch, Lawrence
source	BioRxiv
abstract	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.
has issue date	2020-08-19(xsd:dateTime)
bibo:doi	10.1101/2020.08.13.243303
has license	biorxiv
sha1sum (hex)	8146b93db595e2d97f983fe27ba1c886adc69b9a
schema:url	https://doi.org/10.1101/2020.08.13.243303
resource representing a document's title	Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion
schema:publication	bioRxiv
resource representing a document's body	covid:8146b93db595e2d97f983fe27ba1c886adc69b9a#body_text
is schema:about of	named entity 'furin' named entity 'fusion' named entity 'completely' named entity 'fusion peptide' named entity 'processes' named entity 'Spike' named entity 'SARS-CoV-2' named entity 'infection' named entity 'CRISPR-CAS9 KNOCKOUT' named entity 'INFECTS' named entity 'ORDER' named entity 'ACCEPTOR' named entity 'FURIN' named entity 'TMPRSS2' named entity 'TMPRSS2' named entity 'virus' named entity 'SARS-CoV-2' named entity 'loss' named entity 'prevent' named entity 'mutants' named entity 'Our' named entity 'furin' named entity 'cells' named entity 'acceptor' named entity 'reveal' named entity 'prevent' named entity 'Here' named entity 'reduces' named entity 'furin' named entity 'TMPRSS2' named entity 'SARS-CoV-2' named entity 'furin' named entity 'fusion peptide' named entity 'virion' named entity 'syncytia' named entity 'furin' named entity 'mutants' named entity 'protein' named entity 'virus' named entity 'cell-cell' named entity 'mutation' named entity 'Furin' named entity 'SARS-CoV-2' named entity 'cell fusion' named entity 'SARS-CoV-2' named entity 'donor' named entity 'PCR amplification' named entity 'PMSF' named entity 'viral replication' named entity 'TMPRSS2' named entity 'syncytia' named entity 'pseudoviruses' named entity 'PBS' named entity 'furin' named entity 'lysosomal' named entity 'furin' named entity 'PCR' named entity 'influenza' named entity 'gRNA' named entity 'Immunoblot' named entity 'TMPRSS2' named entity 'cell fusion' named entity 'PCR' named entity 'cloning' named entity 'recombination' named entity 'protease' named entity 'infectivity' named entity '293T cells' named entity 'Vero' named entity 'fusion peptide' named entity 'codon' named entity 'protein' named entity 'trypsinized'

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