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

Abstract

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

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Affiliated Institutions

• Universitätsmedizin Göttingen DE
• LMU Klinikum DE
• Discovery Institute US
• The University of Queensland AU
• Helsinki University Hospital FI
• Sanford Burnham Prebys Medical Discovery Institute US
• University of Zurich CH
• ETH Zurich CH
• University of Göttingen DE
• Finnish Institute for Health and Welfare FI
• University of Helsinki FI
• University of California, Santa Barbara US
• Max Planck Institute of Experimental Medicine DE
• University of Tartu EE
• Park Centre for Mental Health AU
• Ludwig-Maximilians-Universität München DE
• Cancer Research Center US
• German Center for Neurodegenerative Diseases DE
• Munich Cluster for Systems Neurology DE
• Paracelsus Elena Klinik Kassel DE

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