2. Academic Validation
  3. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity

Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity

  • Science. 2020 Nov 13;370(6518):856-860. doi: 10.1126/science.abd2985.
Ludovico Cantuti-Castelvetri # 1 2,  Ravi Ojha # 3,  Liliana D Pedro # 1 2,  Minou Djannatian # 1 2,  Jonas Franz # 4 5 6,  Suvi Kuivanen # 7,  Franziska van der Meer 4,  Katri Kallio 3,  Tuğberk Kaya 1 2 8,  Maria Anastasina 3 9,  Teemu Smura 7,  Lev Levanov 7,  Leonora Szirovicza 7,  Allan Tobi 10,  Hannimari Kallio-Kokko 11,  Pamela Österlund 12,  Merja Joensuu 13,  Frédéric A Meunier 13,  Sarah J Butcher 3 9,  Martin Sebastian Winkler 14,  Brit Mollenhauer 15 16,  Ari Helenius 17,  Ozgun Gokce 8,  Tambet Teesalu 3 18 19,  Jussi Hepojoki 5 20,  Olli Vapalahti 7 11 21,  Christine Stadelmann 4,  Giuseppe Balistreri 22 23,  Mikael Simons 24 2 25
Affiliations

Affiliations

  • 1 Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany.
  • 2 German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
  • 3 Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of Helsinki, Helsinki, Finland.
  • 4 Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
  • 5 Campus Institute for Dynamics of Biological Networks, University of Göttingen, Göttingen, Germany.
  • 6 Max Planck Institute for Experimental Medicine, Göttingen, Germany.
  • 7 Department of Virology, Medicum, University of Helsinki, Helsinki, Finland.
  • 8 Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
  • 9 Helsinki Institute of Life Sciences-Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
  • 10 Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
  • 11 Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • 12 Department of Health Security, Finnish Institute for Health and Welfare (THL), Helsinki, Finland.
  • 13 Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
  • 14 Department of Anesthesiology and Intensive Care Medicine, University Medical Center Göttingen, Göttingen, Germany.
  • 15 Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
  • 16 Paracelsus-Elena-Klinik Kassel, Kassel, Germany.
  • 17 Institute of Biochemistry, ETH Zürich, Zürich, Switzerland.
  • 18 Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • 19 Center for Nanomedicine and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.
  • 20 Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
  • 21 Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
  • 22 Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of Helsinki, Helsinki, Finland. [email protected] [email protected].
  • 23 The Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
  • 24 Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany. [email protected] [email protected].
  • 25 Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.
  • # Contributed equally.
PMID: 33082293 DOI: 10.1126/science.abd2985
Abstract

The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered Furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for Antiviral intervention.

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