tetano
Editor, Senior Moderator
Science
. 2020 Oct 20;eabd2985.
doi: 10.1126/science.abd2985. Online ahead of print.
Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
Ludovico Cantuti-Castelvetri[SUP] #[/SUP][SUP] 1 2 [/SUP], Ravi Ojha[SUP] #[/SUP][SUP] 3 [/SUP], Liliana D Pedro[SUP] #[/SUP][SUP] 1 2 [/SUP], Minou Djannatian[SUP] #[/SUP][SUP] 1 2 [/SUP], Jonas Franz[SUP] #[/SUP][SUP] 4 [/SUP], Suvi Kuivanen[SUP] #[/SUP][SUP] 5 [/SUP], Franziska van der Meer[SUP] 4 [/SUP], Katri Kallio[SUP] 3 [/SUP], Tuğberk Kaya[SUP] 1 2 6 [/SUP], Maria Anastasina[SUP] 3 7 [/SUP], Teemu Smura[SUP] 5 [/SUP], Lev Levanov[SUP] 5 [/SUP], Leonora Szirovicza[SUP] 5 [/SUP], Allan Tobi[SUP] 8 [/SUP], Hannimari Kallio-Kokko[SUP] 9 [/SUP], Pamela ?sterlund[SUP] 10 [/SUP], Merja Joensuu[SUP] 11 [/SUP], Fr?d?ric A Meunier[SUP] 11 [/SUP], Sarah J Butcher[SUP] 3 7 [/SUP], Martin Sebastian Winkler[SUP] 12 [/SUP], Brit Mollenhauer[SUP] 13 [/SUP], Ari Helenius[SUP] 14 [/SUP], Ozgun Gokce[SUP] 6 15 [/SUP], Tambet Teesalu[SUP] 3 16 17 [/SUP], Jussi Hepojoki[SUP] 5 18 [/SUP], Olli Vapalahti[SUP] 5 9 19 [/SUP], Christine Stadelmann[SUP] 4 [/SUP], Giuseppe Balistreri[SUP] 20 15 [/SUP], Mikael Simons[SUP] 21 2 22 [/SUP]
Affiliations
Abstract
The causative agent of coronavirus induced 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. Here, 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 human COVID-19 autopsies revealed SARS-CoV-2 infected cells including olfactory neuronal cells facing the nasal cavity positive for NRP1. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.
. 2020 Oct 20;eabd2985.
doi: 10.1126/science.abd2985. Online ahead of print.
Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
Ludovico Cantuti-Castelvetri[SUP] #[/SUP][SUP] 1 2 [/SUP], Ravi Ojha[SUP] #[/SUP][SUP] 3 [/SUP], Liliana D Pedro[SUP] #[/SUP][SUP] 1 2 [/SUP], Minou Djannatian[SUP] #[/SUP][SUP] 1 2 [/SUP], Jonas Franz[SUP] #[/SUP][SUP] 4 [/SUP], Suvi Kuivanen[SUP] #[/SUP][SUP] 5 [/SUP], Franziska van der Meer[SUP] 4 [/SUP], Katri Kallio[SUP] 3 [/SUP], Tuğberk Kaya[SUP] 1 2 6 [/SUP], Maria Anastasina[SUP] 3 7 [/SUP], Teemu Smura[SUP] 5 [/SUP], Lev Levanov[SUP] 5 [/SUP], Leonora Szirovicza[SUP] 5 [/SUP], Allan Tobi[SUP] 8 [/SUP], Hannimari Kallio-Kokko[SUP] 9 [/SUP], Pamela ?sterlund[SUP] 10 [/SUP], Merja Joensuu[SUP] 11 [/SUP], Fr?d?ric A Meunier[SUP] 11 [/SUP], Sarah J Butcher[SUP] 3 7 [/SUP], Martin Sebastian Winkler[SUP] 12 [/SUP], Brit Mollenhauer[SUP] 13 [/SUP], Ari Helenius[SUP] 14 [/SUP], Ozgun Gokce[SUP] 6 15 [/SUP], Tambet Teesalu[SUP] 3 16 17 [/SUP], Jussi Hepojoki[SUP] 5 18 [/SUP], Olli Vapalahti[SUP] 5 9 19 [/SUP], Christine Stadelmann[SUP] 4 [/SUP], Giuseppe Balistreri[SUP] 20 15 [/SUP], Mikael Simons[SUP] 21 2 22 [/SUP]
Affiliations
- PMID: 33082293
- DOI: 10.1126/science.abd2985
Abstract
The causative agent of coronavirus induced 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. Here, 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 human COVID-19 autopsies revealed SARS-CoV-2 infected cells including olfactory neuronal cells facing the nasal cavity positive for NRP1. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.