The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution
Open accessPublished version of a preprint
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme 2 (ACE2) receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single–amino acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently Asn 501 →Tyr (N501Y), cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change—for example, enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.
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Cited by
Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4 and BA.5
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Imprinted antibody responses against SARS-CoV-2 Omicron sublineages
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“S10a), especially Y501, which has epi-static shifts and enhances hACE2 binding 35 , however, these mutations donotaffecttheneutralizingactivityofTH281andTH132.”
InfluentialSarbecovirus RBD indels and specific residues dictating multi-species ACE2 adaptiveness
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Ketaren, N. E., Mast, F. D., Fridy, P. C., Olivier, J. P., Sanyal, T., Sali, A., Chait, B. T., Rout, M. P., & Aitchison, J. D. (2023) · doi:10.1101/2023.07.14.549041 · Cited by 1
Metadata
- Authors
- Starr, T. N., Greaney, A. J., Hannon, W. W., Loes, A. N., Hauser, K., Dillen, J. R., Ferri, E., Farrell, A. G., Dadonaite, B., McCallum, M., Matreyek, K. A., Corti, D., Veesler, D., Snell, G., & Bloom, J. D.
- Venue
- Science
- Published
- 2022-07-22
- Volume
- 377
- Issue
- 6604
- Pages
- 420-424
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4283646162
- Cited by
- 303
- References
- 62
- FWCI
- 30.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Starr, T. N., Greaney, A. J., Hannon, W. W., Loes, A. N., Hauser, K., Dillen, J. R., Ferri, E., Farrell, A. G., Dadonaite, B., McCallum, M., Matreyek, K. A., Corti, D., Veesler, D., Snell, G., & Bloom, J. D. (2022). Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution. Science. https://doi.org/10.1126/science.abo7896
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