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, Tuğberk Kaya, Maria Anastasina, Teemu Smura, Lev Levanov, Leonóra Szirovicza, Allan Tobi, Hannimari Kallio‐Kokko, Pamela Österlund, Merja Joensuu, Frédéric A. Meunier, Sarah J. Butcher, Martin Sebastian Winkler, Brit Mollenhauer, Ari Helenius, Özgün Gökçe, Tambet Teesalu, Jussi Hepojoki, Olli Vapalahti, Christine Stadelmann, Giuseppe Balistreri, Mikael Simons
Abstract
Another host factor for SARS-CoV-2 Virus-host interactions determine cellular entry and spreading in tissues. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the earlier SARS-CoV use angiotensin-converting enzyme 2 (ACE2) as a receptor; however, their tissue tropism differs, raising the possibility that additional host factors are involved. The spike protein of SARS-CoV-2 contains a cleavage site for the protease furin that is absent from SARS-CoV (see the Perspective by Kielian). Cantuti-Castelvetri et al. now show that neuropilin-1 (NRP1), which is known to bind furin-cleaved substrates, potentiates SARS-CoV-2 infectivity. NRP1 is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial and epithelial cells. Daly et al. found that the furin-cleaved S1 fragment of the spike protein binds directly to cell surface NRP1 and blocking this interaction with a small-molecule inhibitor or monoclonal antibodies reduced viral infection in cell culture. Understanding the role of NRP1 in SARS-CoV-2 infection may suggest potential targets for future antiviral therapeutics. Science , this issue p. 856 , p. 861 ; see also p. 765