Structure, Function, and Evolution of Coronavirus Spike Proteins
Open accessAbstract
The coronavirus spike protein is a multifunctional molecular machine that mediates coronavirus entry into host cells. It first binds to a receptor on the host cell surface through its S1 subunit and then fuses viral and host membranes through its S2 subunit. Two domains in S1 from different coronaviruses recognize a variety of host receptors, leading to viral attachment. The spike protein exists in two structurally distinct conformations, prefusion and postfusion. The transition from prefusion to postfusion conformation of the spike protein must be triggered, leading to membrane fusion. This article reviews current knowledge about the structures and functions of coronavirus spike proteins, illustrating how the two S1 domains recognize different receptors and how the spike proteins are regulated to undergo conformational transitions. I further discuss the evolution of these two critical functions of coronavirus spike proteins, receptor recognition and membrane fusion, in the context of the corresponding functions from other viruses and host cells.
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Before host cell contact, spike is in a metastable pre-fusion trimer that rearranges substantially during virus-cell fusion.
“Prior to contact with the host cell, the S protein is in a metastable pre-fusion conformation and the trimer undergoes substantial rearrangement at the time of virus–cell fusion150,151.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [150]
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- Authors
- Li, F.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Li, Fang
- ORCID
- Li, Fang
- Venue
- Annual Review of Virology
- Publisher
- Annual Reviews
- Published
- 2016-09-29
- Volume
- 3
- Issue
- 1
- Pages
- 237-261
- ISSN
- 2327-056X (ISSN-L)
- 2327-0578
- PMC
- PMC5457962
- OpenAlex
- W2513547424
- Cited by
- 2,740
- References
- 151
- Citations by year
- 2026: 76 · 2025: 137 · 2024: 183 · 2023: 251 · 2022: 441 · 2021: 733 · 2020: 860 · 2019: 26 · 2018: 19 · 2017: 8 · 2016: 3 · 2012: 1
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Virology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI110700, R01AI089728)
- 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 › Epidemiology › Virology and Viral Diseases
- Keywords
- coronavirus spike protein, viral entry, receptor recognition, host cell receptors, viral evolution, spike protein structure, membrane fusion
- MeSH terms
- Humans, Membrane Fusion, Membrane Glycoproteins, Receptors, Virus, Viral Envelope Proteins, Coronavirus, Coronavirus Infections, Virus Attachment, Virus Internalization, Spike Glycoprotein, Coronavirus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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