Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape
Open accessAbstract
Antibody cocktails represent a promising approach to prevent SARS-CoV-2 escape. The determinants for selecting antibody combinations and the mechanism that antibody cocktails prevent viral escape remain unclear. We compared the critical residues in the receptor-binding domain (RBD) used by multiple neutralizing antibodies and cocktails and identified a combination of two antibodies CoV2-06 and CoV2-14 for preventing viral escape. The two antibodies simultaneously bind to non-overlapping epitopes and independently compete for receptor binding. SARS-CoV-2 rapidly escapes from individual antibodies by generating resistant mutations in vitro, but it doesn’t escape from the cocktail due to stronger mutational constraints on RBD-ACE2 interaction and RBD protein folding requirements. We also identified a conserved neutralizing epitope shared between SARS-CoV-2 and SARS-CoV for antibody CoV2-12. Treatments with CoV2-06 and CoV2-14 individually and in combination confer protection in mice. These findings provide insights for rational selection and mechanistic understanding of antibody cocktails as candidates for treating COVID-19.
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The E484K substitution alone confers resistance to several monoclonal antibodies.
“The E484K substitution alone confers resistance to several monoclonal antibodies 9,10 .”
From Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera (2021) · cites this paper as [9]
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References 42 · Cited by 160
- Authors
- Ku, Z., Xie, X., Davidson, E., Ye, X., Su, H., Menachery, V. D., Li, Y., Yuan, Z., Zhang, X., Muruato, A. E., i Escuer, A. G., Tyrell, B., Doolan, K., Doranz, B. J., Wrapp, D., Bates, P. F., McLellan, J. S., Weiss, S. R., Zhang, N., Shi, P.-Y., & An, Z.
- Affiliations
- Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
- The University of Texas Medical Branch at Galveston (US)
- Integral Molecular (United States) (US)
- University of Pennsylvania (US)
- The University of Texas at Austin (US)
- Corresponding author
- Zhang, Ningyan
- Shi, Pei-Yong
- An, Zhiqiang
- ORCID
- Venue
- Nature Communications
- Published
- 2021-01-20
- Volume
- 12
- Issue
- 1
- Pages
- 469-469
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7817669
- OpenAlex
- W3123733204
- Cited by
- 160
- References
- 42
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 9 · 2023: 17 · 2022: 63 · 2021: 59
- FWCI
- 11.68
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-07-01)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Welch Foundation (AU-0042-20030616)
- 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, antibody cocktail, viral immune evasion, receptor binding domain, neutralizing antibodies, epitope overlap, mutational constraint, protein folding, SARS-CoV, COVID-19 treatment, antibody selection
- MeSH terms
- Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Animals, Antibodies, Monoclonal, Antibodies, Viral, Chlorocebus aethiops, Disease Models, Animal, Female, Humans, Immunoglobulin G, Immunoglobulin Fragments, Mice, Inbred BALB C, Models, Molecular, Mutation, Protein Binding, Vero Cells, Mice, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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