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

Science (New York, N.Y.) (2020-10-22)
Ludovico Cantuti-Castelvetri, Ravi Ojha, Liliana D Pedro, Minou Djannatian, Jonas Franz, Suvi Kuivanen, Franziska van der Meer, Katri Kallio, Tuğberk 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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium citrate tribasic hydrate, ReagentPlus®, ≥99%
Sigma-Aldrich
TWEEN® 20, for molecular biology, viscous liquid
Sigma-Aldrich
Silver nitrate, ACS reagent, ≥99.0%
Sigma-Aldrich
Triton X-100, laboratory grade
Supelco
Tris(2-carboxyethyl)phosphine hydrochloride solution, 0.5 M, pH 7.0(aqueous solution; pH was adjusted with ammonium hydroxide)