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

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 neuropi...

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Autores principales: Cantuti-Castelvetri, Ludovico, Ojha, Ravi, Pedro, Liliana D., Djannatian, Minou, Franz, Jonas, Kuivanen, Suvi, van der Meer, Franziska, Kallio, Katri, Kaya, Tuğberk, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857391/
https://www.ncbi.nlm.nih.gov/pubmed/33082293
http://dx.doi.org/10.1126/science.abd2985
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author Cantuti-Castelvetri, Ludovico
Ojha, Ravi
Pedro, Liliana D.
Djannatian, Minou
Franz, Jonas
Kuivanen, Suvi
van der Meer, Franziska
Kallio, Katri
Kaya, Tuğberk
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
author_facet Cantuti-Castelvetri, Ludovico
Ojha, Ravi
Pedro, Liliana D.
Djannatian, Minou
Franz, Jonas
Kuivanen, Suvi
van der Meer, Franziska
Kallio, Katri
Kaya, Tuğberk
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
author_sort Cantuti-Castelvetri, Ludovico
collection PubMed
description 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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spelling pubmed-78573912021-02-05 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, Tuğberk 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 Science Reports 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. American Association for the Advancement of Science 2020-11-13 2020-10-20 /pmc/articles/PMC7857391/ /pubmed/33082293 http://dx.doi.org/10.1126/science.abd2985 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reports
Cantuti-Castelvetri, Ludovico
Ojha, Ravi
Pedro, Liliana D.
Djannatian, Minou
Franz, Jonas
Kuivanen, Suvi
van der Meer, Franziska
Kallio, Katri
Kaya, Tuğberk
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
Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
title Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
title_full Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
title_fullStr Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
title_full_unstemmed Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
title_short Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
title_sort neuropilin-1 facilitates sars-cov-2 cell entry and infectivity
topic Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857391/
https://www.ncbi.nlm.nih.gov/pubmed/33082293
http://dx.doi.org/10.1126/science.abd2985
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