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Cited by 319SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesAnimal Virus Infections Studies

Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design

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Xia, Xuhua·2021·Viruses
DOI 10.3390/v13010109PMC PMC7829931
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Abstract

The spike protein in SARS-CoV-2 (SARS-2-S) interacts with the human ACE2 receptor to gain entry into a cell to initiate infection. Both Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273 vaccine candidates are based on stabilized mRNA encoding prefusion SARS-2-S that can be produced after the mRNA is delivered into the human cell and translated. SARS-2-S is cleaved into S1 and S2 subunits, with S1 serving the function of receptor-binding and S2 serving the function of membrane fusion. Here, I dissect in detail the various domains of SARS-2-S and their functions discovered through a variety of different experimental and theoretical approaches to build a foundation for a comprehensive mechanistic understanding of how SARS-2-S works to achieve its function of mediating cell entry and subsequent cell-to-cell transmission. The integration of structure and function of SARS-2-S in this review should enhance our understanding of the dynamic processes involving receptor binding, multiple cleavage events, membrane fusion, viral entry, as well as the emergence of new viral variants. I highlighted the relevance of structural domains and dynamics to vaccine development, and discussed reasons for the spike protein to be frequently featured in the conspiracy theory claiming that SARS-CoV-2 is artificially created.

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  • S-2P differs from the spike protein in the reference SARS-CoV-2 genome (NC_045512) by two amino acids, i.e., amino acids KV at sites 986 and 987 were replaced by PP.

    “Both mRNA encodes the same S-2P protein [5,6] which differ from the spike protein in the reference SARS-CoV-2 genome (NC_045512) by two amino acids, i.e., amino acids KV at sites 986 and 987 were replaced by PP to stabilize the resulting spike protein in the prefusion state to train the host immune system to recognize the virus before its entry into the host cell [7,8].”

    From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [8]

  • The PP substitution stabilizes the resulting spike protein in the prefusion state to train the host immune system to recognize the virus before its entry into the host cell.

    “Both mRNA encodes the same S-2P protein [5,6] which differ from the spike protein in the reference SARS-CoV-2 genome (NC_045512) by two amino acids, i.e., amino acids KV at sites 986 and 987 were replaced by PP to stabilize the resulting spike protein in the prefusion state to train the host immune system to recognize the virus before its entry into the host cell [7,8].”

    From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [8]

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Cited by

Sorted by citations

Authors
Xia, X.
Affiliations
University of Ottawa (CA)
Corresponding author
Xia, Xuhua
ORCID
Xia, Xuhua
Venue
Viruses
Publisher
MDPI AG
Published
2021-01-14
Volume
13
Issue
1
Pages
109
ISSN
1999-4915 (ISSN-L)
DOI
10.3390/v13010109
PMC
PMC7829931
OpenAlex
W3119453605
Cited by
319
References
8
Citations by year
2026: 21 · 2025: 27 · 2024: 41 · 2023: 71 · 2022: 103 · 2021: 56
FWCI
8.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Viruses (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • uO Research (University of Ottawa) (submittedVersion, public-domain)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • University of Ottawa - Library
Funders
Natural Sciences and Engineering Research Council of Canada (RGPIN/2018-03878)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords
SARS-CoV-2 spike protein, vaccine design, prefusion spike, ACE2 receptor, receptor binding domain, membrane fusion, viral entry, spike protein cleavage, viral variants, BNT162b2, mRNA-1273, conspiracy theories
MeSH terms
Protein Domains, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Humans, Membrane Fusion, Mutation, Protein Binding, Receptors, Virus, Virus Internalization, Protein Stability, Spike Glycoprotein, Coronavirus

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