Global Diversification and Distribution of Coronaviruses With Furin Cleavage Sites
Open accessAbstract
Knowledge about coronaviruses (CoVs) with furin cleavage sites is extremely limited, although these sites mediate the hydrolysis of glycoproteins in plasma membranes required for MERS-CoV or SARS-CoV-2 to enter cells and infect humans. Thus, we have examined the global epidemiology and evolutionary history of SARS-CoV-2 and 248 other CoVs with 86 diversified furin cleavage sites that have been detected in 24 animal hosts in 28 countries since 1954. Besides MERS-CoV and SARS-CoV-2, two of five other CoVs known to infect humans (HCoV-OC43 and HCoV-HKU1) also have furin cleavage sites. In addition, human enteric coronavirus (HECV-4408) has a furin cleavage site and has been detected in humans (first in Germany in 1988), probably via spillover events from bovine sources. In conclusion, the presence of furin cleavage sites might explain the polytropic nature of SARS-CoV-2- and SARS-CoV-2-like CoVs, which would be helpful for ending the COVID-19 pandemic and preventing outbreaks of novel CoVs.
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Furin cleavage sites occur naturally in almost every coronavirus family, but they have not been observed in other SARS-related coronaviruses.
“Furin cleavage sites are found naturally in almost every family of coronavirus,50, 51 although they have not been observed in other SARS-related coronaviruses (subgenus Sarbecoronavirus).”
From The Lancet Commission on lessons for the future from the COVID-19 pandemic (2022) · cites this paper as [51]
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Hoffmann, M., Kleine-Weber, H., & Pöhlmann, S. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.04.022 · Cited by 1,852 · see citing works
An Infectious cDNA Clone of SARS-CoV-2
Xie, X., Muruato, A., Lokugamage, K. G., Narayanan, K., Zhang, X., Zou, J., Liu, J., Schindewolf, C., Bopp, N. E., Aguilar, P. V., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.04.004 · Cited by 647 · see citing works
Wrobel, A. G., Benton, D. J., Xu, P., Roustan, C., Martin, S. R., Rosenthal, P. B., Skehel, J. J., & Gamblin, S. J. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0468-7 · Cited by 544 · see citing works
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The Lancet Commission on lessons for the future from the COVID-19 pandemic
Sachs, J. D., Karim, S. S. A., Aknin, L., Allen, J., Brosbøl, K., Colombo, F., Barron, G. C., Espinosa, M. F., Gaspar, V., Gaviria, A., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(22)01585-9 · Cited by 842 · see citing works
- Authors
- Liu, X., Wu, Q., & Zhang, Z.
- Affiliations
- Yunnan University (CN)
- Corresponding author
- Zhang, Zhigang
- Venue
- Frontiers in Microbiology
- Publisher
- Frontiers Media SA
- Published
- 2021-10-07
- Volume
- 12
- Pages
- 649314-649314
- ISSN
- 1664-302X (ISSN-L)
- PMC
- PMC8529245
- OpenAlex
- W3207331348
- Cited by
- 32
- References
- 3
- Citations by year
- 2026: 1 · 2025: 13 · 2024: 6 · 2023: 3 · 2022: 8 · 2021: 1
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Microbiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Key Research and Development Program of China (31970571, 2019QZKK0503, 2018YFC2000500))
- 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
- coronavirus, furin cleavage site, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-HKU1, animal hosts, global distribution, viral evolution, zoonotic spillover, COVID-19 pandemic, coronavirus epidemiology
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