Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity PMID: 33082293

Target-related Cytokines

2026-09-23

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

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.

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.