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Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity.
Cantuti-Castelvetri, Ludovico; Ojha, Ravi; Pedro, Liliana D; Djannatian, Minou; Franz, Jonas; Kuivanen, Suvi; van der Meer, Franziska; Kallio, Katri; Kaya, Tugberk; Anastasina, Maria; Smura, Teemu; Levanov, Lev; Szirovicza, Leonora; Tobi, Allan; Kallio-Kokko, Hannimari; Österlund, Pamela; Joensuu, Merja; Meunier, Frédéric A; Butcher, Sarah J; Winkler, Martin Sebastian; Mollenhauer, Brit; Helenius, Ari; Gokce, Ozgun; Teesalu, Tambet; Hepojoki, Jussi; Vapalahti, Olli; Stadelmann, Christine; Balistreri, Giuseppe; Simons, Mikael.
  • Cantuti-Castelvetri L; Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany.
  • Ojha R; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
  • Pedro LD; Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of Helsinki, Helsinki, Finland.
  • Djannatian M; Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany.
  • Franz J; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
  • Kuivanen S; Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany.
  • van der Meer F; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
  • Kallio K; Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
  • Kaya T; Campus Institute for Dynamics of Biological Networks, University of Göttingen, Göttingen, Germany.
  • Anastasina M; Max Planck Institute for Experimental Medicine, Göttingen, Germany.
  • Smura T; Department of Virology, Medicum, University of Helsinki, Helsinki, Finland.
  • Levanov L; Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
  • Szirovicza L; Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of Helsinki, Helsinki, Finland.
  • Tobi A; Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany.
  • Kallio-Kokko H; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
  • Österlund P; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
  • Joensuu M; Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of Helsinki, Helsinki, Finland.
  • Meunier FA; Helsinki Institute of Life Sciences-Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
  • Butcher SJ; Department of Virology, Medicum, University of Helsinki, Helsinki, Finland.
  • Winkler MS; Department of Virology, Medicum, University of Helsinki, Helsinki, Finland.
  • Mollenhauer B; Department of Virology, Medicum, University of Helsinki, Helsinki, Finland.
  • Helenius A; Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
  • Gokce O; Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • Teesalu T; Department of Health Security, Finnish Institute for Health and Welfare (THL), Helsinki, Finland.
  • Hepojoki J; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
  • Vapalahti O; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
  • Stadelmann C; Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences Research Program, University of Helsinki, Helsinki, Finland.
  • Balistreri G; Helsinki Institute of Life Sciences-Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
  • Simons M; Department of Anesthesiology and Intensive Care Medicine, University Medical Center Göttingen, Göttingen, Germany.
Science ; 370(6518): 856-860, 2020 11 13.
Article in English | MEDLINE | ID: covidwho-883299
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Neuropilin-1 / Virus Internalization / Spike Glycoprotein, Coronavirus / Betacoronavirus Language: English Journal: Science Year: 2020 Document Type: Article Affiliation country: Science.abd2985

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Neuropilin-1 / Virus Internalization / Spike Glycoprotein, Coronavirus / Betacoronavirus Language: English Journal: Science Year: 2020 Document Type: Article Affiliation country: Science.abd2985