Another host factor for SARS-CoV-2 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. 765 NRP1 serves as a host factor for SARS-CoV-2 infection and may potentially provide a therapeutic target for COVID-19. 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.
【초록키워드】 COVID-19, coronavirus disease, viruses, SARS-CoV-2, viral infection, ACE2, coronavirus, furin, antibody, SARS-CoV, SARS-COV-2 infection, monoclonal antibody, nasal, protease, angiotensin-converting enzyme 2, Autopsy, Spike protein, furin cleavage site, Cell culture, understanding, target, NRP1, epithelial cells, antiviral therapeutics, cellular entry, mutant, virus receptor, inhibitor, expression, monoclonal, Interaction, Analysis, Olfactory epithelium, therapeutic target, host cells, tissue tropism, cofactor, Science, endothelial, acute respiratory syndrome, Factor, tissues, cleavage site, antiviral intervention, Host, Cell, bind, pathological, highest, blocked, significantly, involved, reduced, determine, the spike protein, abundantly expressed, furin-cleaved substrates, raising, SARS-CoV-2 cell, 【제목키워드】 Neuropilin-1, facilitate, SARS-CoV-2 cell,