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

Ludovico Cantuti-Castelvetri; Ravi Ojha; Liliana D. Pedro; Minou Djannatian; Jonas Franz; Suvi Kuivanen; Franziska van der Meer; Katri Kallio; Tuǧberk Kaya; Maria Anastasina; Teemu Smura; Lev Levanov; Leonora Szirovicza; Allan Tobi; Hannimari Kallio-Kokko; Pamela Österlund; Merja Joensuu; Frédéric A. Meunier; Sarah J. Butcher; Martin Sebastian Winkler; Brit Mollenhauer; Ari Helenius; Ozgun Gokce; Tambet Teesalu; Jussi Hepojoki; Olli Vapalahti; Christine Stadelmann; Giuseppe Balistreri; Mikael Simons

doi:10.1126/science.abd2985

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

Ludovico Cantuti-Castelvetri
, Ravi Ojha
, Liliana D. Pedro
, Minou Djannatian
, Jonas Franz
, Suvi Kuivanen
, Franziska van der Meer
, Katri Kallio
, Tuǧberk Kaya
, Maria Anastasina
, Teemu Smura
, Lev Levanov
, Leonora Szirovicza
, Allan Tobi
, Hannimari Kallio-Kokko
, Pamela Österlund
, Merja Joensuu
, Frédéric A. Meunier
, Sarah J. Butcher
, Martin Sebastian Winkler

Brit Mollenhauer, Ari Helenius, Ozgun Gokce, Tambet Teesalu, Jussi Hepojoki, Olli Vapalahti, Christine Stadelmann, Giuseppe Balistreri, Mikael Simons

Medicine and Health

Technical University of Munich
German Center for Neurodegenerative Diseases (DZNE)
University of Helsinki
University Medical Center
Georg-August-Universität Göttingen
Max Planck Institute of Experimental Medicine
Ludwig-Maximilians-Universität München
University of Tartu
National Institute for Health and Welfare
University of Queensland
Paracelsus-Elena-Klinik
ETH Zürich
Burnham Institute for Medical Research
University of California, Santa Barbara
University of Zurich
Munich Cluster for Systems Neurology (SyNergy)

Research output: Contribution to journal › Article › peer-review

1541 Scopus citations

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.

Original language	English
Article number	abd2985
Journal	Science
Volume	370
Issue number	6518
DOIs	https://doi.org/10.1126/science.abd2985
State	Published - 13 Nov 2020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1126/science.abd2985

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Cantuti-Castelvetri, L., Ojha, R., Pedro, L. D., Djannatian, M., Franz, J., Kuivanen, S., van der Meer, F., Kallio, K., Kaya, T., Anastasina, M., Smura, T., Levanov, L., Szirovicza, L., Tobi, A., Kallio-Kokko, H., Österlund, P., Joensuu, M., Meunier, F. A., Butcher, S. J., ... Simons, M. (2020). Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science, 370(6518), Article abd2985. https://doi.org/10.1126/science.abd2985

@article{1f329f17640140bb98b117759a442560,

title = "Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity",

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.",

author = "Ludovico Cantuti-Castelvetri and Ravi Ojha and Pedro, \{Liliana D.\} and Minou Djannatian and Jonas Franz and Suvi Kuivanen and \{van der Meer\}, Franziska and Katri Kallio and Tuǧberk Kaya and Maria Anastasina and Teemu Smura and Lev Levanov and Leonora Szirovicza and Allan Tobi and Hannimari Kallio-Kokko and Pamela {\"O}sterlund and Merja Joensuu and Meunier, \{Fr{\'e}d{\'e}ric A.\} and Butcher, \{Sarah J.\} and Winkler, \{Martin Sebastian\} and Brit Mollenhauer and Ari Helenius and Ozgun Gokce and Tambet Teesalu and Jussi Hepojoki and Olli Vapalahti and Christine Stadelmann and Giuseppe Balistreri and Mikael Simons",

year = "2020",

month = nov,

day = "13",

doi = "10.1126/science.abd2985",

language = "English",

volume = "370",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6518",

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Cantuti-Castelvetri, L, Ojha, R, Pedro, LD, Djannatian, M, Franz, J, Kuivanen, S, van der Meer, F, Kallio, K, Kaya, T, Anastasina, M, Smura, T, Levanov, L, Szirovicza, L, Tobi, A, Kallio-Kokko, H, Österlund, P, Joensuu, M, Meunier, FA, Butcher, SJ, Winkler, MS, Mollenhauer, B, Helenius, A, Gokce, O, Teesalu, T, Hepojoki, J, Vapalahti, O, Stadelmann, C, Balistreri, G & Simons, M 2020, 'Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity', Science, vol. 370, no. 6518, abd2985. https://doi.org/10.1126/science.abd2985

TY - JOUR

T1 - Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity

AU - Cantuti-Castelvetri, Ludovico

AU - Ojha, Ravi

AU - Pedro, Liliana D.

AU - Djannatian, Minou

AU - Franz, Jonas

AU - Kuivanen, Suvi

AU - van der Meer, Franziska

AU - Kallio, Katri

AU - Kaya, Tuǧberk

AU - Anastasina, Maria

AU - Smura, Teemu

AU - Levanov, Lev

AU - Szirovicza, Leonora

AU - Tobi, Allan

AU - Kallio-Kokko, Hannimari

AU - Österlund, Pamela

AU - Joensuu, Merja

AU - Meunier, Frédéric A.

AU - Butcher, Sarah J.

AU - Winkler, Martin Sebastian

AU - Mollenhauer, Brit

AU - Helenius, Ari

AU - Gokce, Ozgun

AU - Teesalu, Tambet

AU - Hepojoki, Jussi

AU - Vapalahti, Olli

AU - Stadelmann, Christine

AU - Balistreri, Giuseppe

AU - Simons, Mikael

PY - 2020/11/13

Y1 - 2020/11/13

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85094613777

U2 - 10.1126/science.abd2985

DO - 10.1126/science.abd2985

M3 - Article

C2 - 33082293

AN - SCOPUS:85094613777

SN - 0036-8075

VL - 370

JO - Science

JF - Science

IS - 6518

M1 - abd2985

ER -

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

Abstract

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