Neuropilin-1 is a Host Factor for SARS-CoV-2 Infection

Daly, James L. and Simonetti, Boris and Klein, Katja and Chen, Kai-En and Kavanagh Williamson, Maia and Antón-Plágaro, Carlos and Shoemark, Deborah K. and Simón-Gracia, Lorena and Bauer, Michael and Hollandi, Réka and Greber, Urs F. and Horváth, Péter and Sessions, Richard B. and Helenius, Ari and Hiscox, Julian A. and Teesalu, Tambet and Matthews, David A. and Davidson, Andrew D. and Collins, Brett M. and Cullen, Peter J. and Yamauchi, Yohei (2020) Neuropilin-1 is a Host Factor for SARS-CoV-2 Infection. SCIENCE, 370 (6518). pp. 861-865. ISSN 0036-8075 (print); 1095-9203 (online)

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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.

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