PT  - JOURNAL ARTICLE
AU  - Daly, James L.
AU  - Simonetti, Boris
AU  - Klein, Katja
AU  - Chen, Kai-En
AU  - Williamson, Maia Kavanagh
AU  - Antón-Plágaro, Carlos
AU  - Shoemark, Deborah K.
AU  - Simón-Gracia, Lorena
AU  - Bauer, Michael
AU  - Hollandi, Reka
AU  - Greber, Urs F.
AU  - Horvath, Peter
AU  - Sessions, Richard B.
AU  - Helenius, Ari
AU  - Hiscox, Julian A.
AU  - Teesalu, Tambet
AU  - Matthews, David A.
AU  - Davidson, Andrew D.
AU  - Collins, Brett M.
AU  - Cullen, Peter J.
AU  - Yamauchi, Yohei
TI  - Neuropilin-1 is a host factor for SARS-CoV-2 infection
AID  - 10.1126/science.abd3072
DP  - 2020 Nov 13
TA  - Science
PG  - 861--865
VI  - 370
IP  - 6518
4099  - http://science.sciencemag.org/content/370/6518/861.short
4100  - http://science.sciencemag.org/content/370/6518/861.full
SO  - Science2020 Nov 13; 370
AB  - 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. 765Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), uses the viral spike (S) protein for host cell attachment and entry. The host protease furin cleaves the full-length precursor S glycoprotein into two associated polypeptides: S1 and S2. Cleavage of S generates a polybasic Arg-Arg-Ala-Arg carboxyl-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface neuropilin-1 (NRP1) and NRP2 receptors. We used x-ray crystallography and biochemical approaches to show that the S1 CendR motif directly bound NRP1. Blocking this interaction by RNA interference or selective inhibitors reduced SARS-CoV-2 entry and infectivity in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection and may potentially provide a therapeutic target for COVID-19.