Cell entry mechanisms of SARS-CoV-2
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Significance: A key to curbing SARS-CoV-2 is to understand how it enters cells. SARS-CoV-2 and SARS-CoV both use human ACE2 as entry receptor and human proteases as entry activators. Using biochemical and pseudovirus entry assays and SARS-CoV as a comparison, we have identified key cell entry mechanisms of SARS-CoV-2 that potentially contribute to the immune evasion, cell infectivity, and wide spread of the virus. This study also clarifies conflicting reports from recent studies on cell entry of SARS-CoV-2. Finally, by highlighting the potency and the evasiveness of SARS-CoV-2, the study provides insight into intervention strategies that target its cell entry mechanisms.
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The SARS-CoV-2 spike protein binds to its receptor angiotensin-converting enzyme 2 (ACE2) on the host cell surface.
“The spike protein binds to its receptor on the host cell surface, angiotensin-converting enzyme 2 (ref.118).”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [118]
The attached SARS-CoV-2 spike protein is cut by transmembrane serine protease 2, inducing a conformational change that exposes the fusion peptide and facilitates fusion with the cell or endosomal membrane.
“The attached spike protein is then cut open by the cell’s transmembrane serine protease 2, which induces a conformational change that exposes the spike protein’s fusion peptide and facilitates fusion with the cell or endosomal membrane118.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [118]
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- Authors
- Shang, J., Wan, Y., Luo, C., Ye, G., Geng, Q., Auerbach, A., & Li, F.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Li, Fang
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-05-06
- Volume
- 117
- Issue
- 21
- Pages
- 11727-11734
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC7260975
- OpenAlex
- W3022435472
- Cited by
- 3,142
- References
- 48
- Citations by year
- 2026: 78 · 2025: 171 · 2024: 257 · 2023: 444 · 2022: 746 · 2021: 993 · 2020: 450 · 2019: 1
- FWCI
- 87.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R01AI089728, R01AI110700)
- 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, COVID-19 pandemic, viral entry, spike protein, receptor binding domain, ACE2 receptor, furin protease, proteolytic activation, SARS-CoV, receptor binding affinity, immune evasion, pseudovirus entry
- MeSH terms
- Protein Domains, Receptors, Coronavirus, Angiotensin-Converting Enzyme 2, Cell Line, Humans, Peptidyl-Dipeptidase A, Receptors, Virus, Virus Activation, Severe acute respiratory syndrome-related coronavirus, Virus Internalization, Immune Evasion, Spike Glycoprotein, Coronavirus
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