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. [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.