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

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.
Mesh Terms:
Amino Acid Motifs, Angiotensin-Converting Enzyme 2, Antibodies, Monoclonal, Betacoronavirus, COVID-19, Caco-2 Cells, Coronavirus Infections, Crystallography, X-Ray, Furin, HeLa Cells, Humans, Mutagenesis, Site-Directed, Neuropilin-1, Pandemics, Peptide Fragments, Peptidyl-Dipeptidase A, Pneumonia, Viral, Protein Binding, Protein Interaction Domains and Motifs, RNA Interference, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Virus Internalization
Science
Date: Dec. 13, 2019
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