Neuropilin-1 is a host factor for SARS-CoV-2 infection.

Neuropilin-1 is a host factor for SARS-CoV-2 infection.

Science (New York, N.Y.) (2020-10-22)

James L Daly, Boris Simonetti, Katja Klein, Kai-En Chen, Maia Kavanagh Williamson, Carlos Antón-Plágaro, Deborah K Shoemark, Lorena Simón-Gracia, Michael Bauer, Reka Hollandi, Urs F Greber, Peter Horvath, Richard B Sessions, Ari Helenius, Julian A Hiscox, Tambet Teesalu, David A Matthews, Andrew D Davidson, Brett M Collins, Peter J Cullen, Yohei Yamauchi

PMID33082294

ABSTRACT

Severe 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.

MATERIALS

Product Number

Brand

Product Description

SML3408

Sigma-Aldrich

EG00229 trifluoroacetate, ≥98% (HPLC)

BR701330

BRAND^® 96-well microplate, U-bottom, round bottom, non-sterile