| Literature DB >> 33082294 |
James L Daly1, Boris Simonetti2, Katja Klein3, Kai-En Chen4, Maia Kavanagh Williamson3, Carlos Antón-Plágaro1, Deborah K Shoemark5, Lorena Simón-Gracia6, Michael Bauer7, Reka Hollandi8, Urs F Greber7, Peter Horvath8,9, Richard B Sessions1, Ari Helenius10, Julian A Hiscox11,12, Tambet Teesalu6, David A Matthews3, Andrew D Davidson3, Brett M Collins4, Peter J Cullen2, Yohei Yamauchi13,14.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), uses the viral spike (S) protein for host cell attachment and entry. The host protease furin cleaves the full-length precursor S glycoprotein into two associated polypeptides: S1 and S2. Cleavage of S generates a polybasic Arg-Arg-Ala-Arg carboxyl-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface neuropilin-1 (NRP1) and NRP2 receptors. We used x-ray crystallography and biochemical approaches to show that the S1 CendR motif directly bound NRP1. Blocking this interaction by RNA interference or selective inhibitors reduced SARS-CoV-2 entry and infectivity in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection and may potentially provide a therapeutic target for COVID-19.Entities:
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Year: 2020 PMID： 33082294 PMCID： PMC7612957 DOI： 10.1126/science.abd3072
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714