Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection
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Abstract
Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans.
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The spike protein is cleaved by TMPRSS2 and furin at the S1/S2 polybasic cleavage site PRRA, whose arginine residues enable high cleavability.
“The spike protein is cleaved by host type II transmembrane serine proteases (TMPRSS2) and furin at the S1/S2 polybasic cleavage site (PRRA) having arginine residues that empower the high cleavability (S2) [16, 17].”
From Waves and variants of SARS-CoV-2: understanding the causes and effect of the COVID-19 catastrophe (2022) · cites this paper as [16]
The Results section (page unavailable) identifies an arginine-containing RXXR motif at the S1/S2 cleavage site of the MERS, Uganda, and HKU5 spikes, and reports trypsin-dependent spike cleavage. It does not identify a PRRA site, show cleavage by TMPRSS2 or furin, or establish that PRRA's arginines confer high cleavability. (LLM, conf=0.86)
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“The spike protein is cleaved by host type II transmembrane serine proteases (TMPRSS2) and furin at the S1/S2 polybasic cleavage site (PRRA) having arginine residues that empower the high cleavability (S2) [16, 17].”
Background
- Authors
- Menachery, V. D., Dinnon, K. H., Yount, B. L., McAnarney, E. T., Gralinski, L. E., Hale, A., Graham, R. L., Scobey, T., Anthony, S. J., Wang, L., Graham, B., Randell, S. H., Lipkin, W. I., & Baric, R. S.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Columbia University (US)
- National Institute of Allergy and Infectious Diseases (US)
- Corresponding author
- Baric, Ralph S.
- ORCID
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2020-02-14
- Volume
- 94
- Issue
- 5
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC7022341
- OpenAlex
- W2994156659
- Cited by
- 205
- References
- 59
- Citations by year
- 2026: 5 · 2025: 19 · 2024: 15 · 2023: 19 · 2022: 26 · 2021: 52 · 2020: 67 · 2019: 2
- FWCI
- 28.16
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Journal of Virology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Allergy and Infectious Diseases (U19AI109761, AI110700)
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK065988)
- United States Agency for International Development (GHN-A-OO-09-00010-00)
- HHS | NIH | National Institute on Aging (R00AG049092)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Zoonotic diseases and public health
- Keywords
- zoonotic coronaviruses, bat coronaviruses, trypsin, proteolytic cleavage, spike protein, receptor binding, viral entry, coronavirus emergence, gastrointestinal infections, zoonotic transmission
- MeSH terms
- Animals, Chlorocebus aethiops, Chiroptera, Humans, Receptors, Virus, Trypsin, Vero Cells, Zoonoses, Coronavirus Infections, Caco-2 Cells, Spike Glycoprotein, Coronavirus, Middle East Respiratory Syndrome Coronavirus
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