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Proteolytic Cleavage of the SARS-CoV-2 Spike Protein and the Role of the Novel S1/S2 Site

11 Pages Posted: 5 May 2020 Publication Status: Review Complete

See all articles by Javier Jaimes

Javier Jaimes

Cornell University - Department of Microbiology and Immunology

Jean Millet

University of Paris-Saclay - Virologie et Immunologie Moléculaires

Gary Whittaker

Cornell University - Department of Microbiology and Immunology

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19) has rapidly spread from an initial outbreak in Wuhan, China in December 2019 to the rest of the world within a few months. On March 11th 2020, the rapidly evolving COVID-19 situation was characterized as a pandemic by the WHO. Much attention has been drawn to the origin of SARS-CoV-2, a virus which is related to the lineage B betacoronavirus SARS-CoV and SARS-related coronaviruses found in bat species. The closest known relative to SARS-CoV-2 is a bat coronavirus named RaTG13 (BatCoV-RaTG13). Early characterizations of the SARS-CoV-2 genome revealed the existence of a distinct 4 amino acid insert (underlined, SPRRAR↓S),  found within the spike (S) protein, at a position termed the S1/S2 site located at the interface between the S1 receptor binding subunit and the S2 fusion subunit. Notably, this S1/S2 insert appears to be distinguishing feature among SARS-related sequences and introduces a potential cleavage site for the protease furin. Here, we investigate the potential role of this novel S1/S2 cleavage site and present direct biochemical evidence for proteolytic processing by a variety of proteases, including furin, trypsin-like proteases and cathepsins. We discuss these findings in the broader context of the origin of SARS-CoV-2, viral stability and transmission.

Funding: Work in the author’s laboratory is supported by the National Institutes of Health (research grant R01AI35270).

Suggested Citation

Jaimes, Javier and Millet, Jean and Whittaker, Gary, Proteolytic Cleavage of the SARS-CoV-2 Spike Protein and the Role of the Novel S1/S2 Site. Available at SSRN: https://ssrn.com/abstract=3581359 or http://dx.doi.org/10.2139/ssrn.3581359
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Javier Jaimes

Cornell University - Department of Microbiology and Immunology

United States

Jean Millet

University of Paris-Saclay - Virologie et Immunologie Moléculaires

France

Gary Whittaker (Contact Author)

Cornell University - Department of Microbiology and Immunology ( email )

United States

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