2. Academic Validation
  3. Neuropilin-1 is a host factor for SARS-CoV-2 infection

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

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. [email protected] [email protected] [email protected].
  • 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. [email protected] [email protected] [email protected].
  • 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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