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


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


SARS-CoV-2, the causative agent of 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 C-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) receptors. Here, we used X-ray crystallography and biochemical approaches to show that the S1 CendR motif directly bound NRP1. Blocking this interaction using RNAi 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.





Research Themes:

2. Diagnostic and Host Response