Neuropilin-1 is a host factor for SARS-CoV-2 infection

Science. 2020 Nov 13;370(6518):861-865. doi: 10.1126/science.abd3072.

James L Daly ^# ¹, Boris Simonetti ^# ², Katja Klein ^# ³, Kai-En Chen ^# ⁴, Maia Kavanagh Williamson ^# ³, Carlos Antón-Plágaro ^# ¹, Deborah K Shoemark ⁵, Lorena Simón-Gracia ⁶, Michael Bauer ⁷, Reka Hollandi ⁸, Urs F Greber ⁷, Peter Horvath ⁸ ⁹, Richard B Sessions ¹, Ari Helenius ¹⁰, Julian A Hiscox ¹¹ ¹², Tambet Teesalu ⁶, David A Matthews ³, Andrew D Davidson ³, Brett M Collins ⁴, Peter J Cullen ², Yohei Yamauchi ¹³ ¹⁴

Affiliations

1 School of Biochemistry, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
2 School of Biochemistry, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK. bs13866@bristol.ac.uk pete.cullen@bristol.ac.uk yohei.yamauchi@bristol.ac.uk.
3 School of Cellular and Molecular Medicine, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
4 Institute for Molecular Bioscience, the University of Queensland, St. Lucia, QLD 4072, Australia.
5 School of Biochemistry and BrisSynBio Centre, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
6 Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
7 Department of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
8 Synthetic and Systems Biology Unit, Biological Research Centre (BRC), Szeged, Hungary.
9 Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
10 Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.
11 Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
12 Singapore Immunology Network, Agency for Science, Technology, and Research, 138648, Singapore.
13 School of Cellular and Molecular Medicine, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK. bs13866@bristol.ac.uk pete.cullen@bristol.ac.uk yohei.yamauchi@bristol.ac.uk.
14 Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
# Contributed equally.

PMID: 33082294 DOI: 10.1126/science.abd3072

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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