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A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin
Open accessAbstract
The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health.Communicated by Ramaswamy H. Sarma.
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“Although the proximal origins are unknown, SARS-CoV-2 is thought to derive from a bat SARS-CoV-related coronavirus with a furin cleavage site that enhances the capacity of the virus to infect human cells.48, 49”
From The Lancet Commission on lessons for the future from the COVID-19 pandemic (2022) · cites this paper as [49]
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Tonouchi, K., Sakai, H., Kajihara, R., Shimizu, S., Fukuda, H., Otagiri, H., Matsuzawa, K., & Kurita, H. (2026) · Research Square · doi:10.21203/rs.3.rs-11242603/v1
Metadata
- Authors
- Hasan, A., Paray, B. A., Hussain, A., Qadir, F. A., Attar, F., Aziz, F. M., Sharifi, M., Derakhshankhah, H., Rasti, B., Mehrabi, M., Shahpasand, K., Saboury, A. A., & Falahati, M.
- Affiliations
- Qatar University (QA)
- King Saud University (SA)
- Manipal Academy of Higher Education, Dubai (AE)
- Salahaddin University-Erbil (IQ)
- Standard Research Institute (IR)
- Islamic Azad University, Tehran (IR)
- Kermanshah University of Medical Sciences (IR)
- Islamic Azad University, Lahijan Branch (IR)
- Royan Institute (IR)
- University of Tehran (IR)
- Corresponding author
- Hasan, Anwarul
- Falahati, Mojtaba
- ORCID
- Venue
- Journal of Biomolecular Structure and Dynamics
- Publisher
- Informa UK Limited
- Published
- 2020-04-22
- Volume
- 39
- Issue
- 8
- Pages
- 3025-3033
- ISSN
- 0739-1102 (ISSN-L)
- 1538-0254
- PMC
- PMC7189411
- OpenAlex
- W3015385976
- Cited by
- 293
- References
- 84
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 18 · 2023: 24 · 2022: 40 · 2021: 83 · 2020: 115
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Biomolecular Structure and Dynamics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Qatar University QSpace (Qatar University) (submittedVersion)
- Funders
- Qatar Foundation (GCC-2017-005, NPRP10-120-170-211)
- Fonds National de la Recherche Luxembourg
- Qatar University (GCC-2017-005)
- Qatar National Research Fund (NPRP10, NPRP10-120-170-211, GCC-2017-005)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, spike protein, furin cleavage site, angiotensin-converting enzyme 2, viral entry, host cell receptors, S1/S2 cleavage, small molecule inhibitors, antiviral drug discovery, coronavirus vaccines
- MeSH terms
- Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Angiotensins, Humans, Furin, Spike Glycoprotein, Coronavirus
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