Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity

TLDR

SARS‑CoV‑2 causes COVID‑19, and viral tissue tropism depends on host cell receptors and entry cofactors. Our data provide insight into SARS‑CoV‑2 cell infectivity and define a potential target for antiviral intervention. NRP1 markedly enhances SARS‑CoV‑2 infectivity, an effect blocked by an anti‑NRP1 antibody, while a furin‑cleavage‑site mutant is NRP1‑independent, and infected NRP1‑positive cells were found in human olfactory epithelium.

Abstract

The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.