• James L Daly, Boris Simonetti, Katja Klein, Kai-En Chen, Maia Kavanagh Williamson, Carlos Antón-Plágaro, Deborah K Shoemark, Lorena Simón-Gracia, Michael Bauer, Reka Hollandi, Urs F Greber, Peter Horvath, Richard B Sessions, Ari Helenius, Julian A Hiscox, Tambet Teesalu, David A Matthews, Andrew D Davidson, Brett M Collins, Peter J Cullen, and Yohei Yamauchi.
• School of Biochemistry, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
• Science. 2020 Nov 13; 370 (6518): 861-865.

AbstractSevere 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.Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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