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

By Ludovico Cantuti-Castelvetri, Ravi Ojha, Liliana D Pedro, Minou Djannatian, J. Franz, S. Kuivanen, F. van der Meer, Katri Kallio, Tugberk Kaya, Maria Anastasina and 19 more. Science, 2020

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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.

Subfields: Biomedical Engineering, Infectious Diseases, Nutrition and Dietetics

View Paper: https://www.semanticscholar.org/paper/02d578d3b83b69f4f53d6ca292bd8fa27fac0577

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Citations in the corpus

• Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein (2021, neutral): “Virus attachment to cells can differ in diverse cells, likely because of the capacity of SARS-CoV-2 to use multiple attachment factors including heparan sulfates, hACE2, TAM receptors, and possibly other molecules (Cantuti-Castelvetri et al., 2020; Chen et al., 2020; Chiodo et al., 2020; Clausen et ”
• COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas (2021, positive): “We then examined host factors recently reported to be relevant to SARS-CoV-2 entry in our data (Cantuti-Castelvetri et al., 2020; Daly et al., 2020; Singh et al., 2020; Tang et al., 2020) and found that BSG and TFRC demonstrated correlations with the abundance of viral RNA in different cell types (F”