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

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.