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Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity.
Science. 2021 08 06; 373(6555)Sci

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike mutations enable increased transmission and antibody resistance. We combined cryo-electron microscopy (cryo-EM), binding, and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans, and others that originated and spread in human populations. All variants showed increased angiotensin-converting enzyme 2 (ACE2) receptor binding and increased propensity for receptor binding domain (RBD)-up states. While adaptation to mink resulted in spike destabilization, the B.1.1.7 (UK) spike balanced stabilizing and destabilizing mutations. A local destabilizing effect of the RBD E484K mutation was implicated in resistance of the B.1.1.28/P.1 (Brazil) and B.1.351 (South Africa) variants to neutralizing antibodies. Our studies revealed allosteric effects of mutations and mechanistic differences that drive either interspecies transmission or escape from antibody neutralization.

Authors+Show Affiliations

Duke Human Vaccine Institute, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA. Department of Medicine, Duke University, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA. Department of Surgery, Duke University, Durham, NC 27710, USA. Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA. Department of Immunology, Duke University, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA. Department of Medicine, Duke University, Durham, NC 27710, USA.Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA. Department of Medicine, Duke University, Durham, NC 27710, USA. Department of Immunology, Duke University, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA. rory.henderson@duke.edu priyamvada.acharya@duke.edu. Department of Medicine, Duke University, Durham, NC 27710, USA.Duke Human Vaccine Institute, Durham, NC 27710, USA. rory.henderson@duke.edu priyamvada.acharya@duke.edu. Department of Surgery, Duke University, Durham, NC 27710, USA. Department of Biochemistry, Duke University, Durham, NC 27710, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34168071

Citation

Gobeil, Sophie M-C, et al. "Effect of Natural Mutations of SARS-CoV-2 On Spike Structure, Conformation, and Antigenicity." Science (New York, N.Y.), vol. 373, no. 6555, 2021.
Gobeil SM, Janowska K, McDowell S, et al. Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity. Science. 2021;373(6555).
Gobeil, S. M., Janowska, K., McDowell, S., Mansouri, K., Parks, R., Stalls, V., Kopp, M. F., Manne, K., Li, D., Wiehe, K., Saunders, K. O., Edwards, R. J., Korber, B., Haynes, B. F., Henderson, R., & Acharya, P. (2021). Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity. Science (New York, N.Y.), 373(6555). https://doi.org/10.1126/science.abi6226
Gobeil SM, et al. Effect of Natural Mutations of SARS-CoV-2 On Spike Structure, Conformation, and Antigenicity. Science. 2021 08 6;373(6555) PubMed PMID: 34168071.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity. AU - Gobeil,Sophie M-C, AU - Janowska,Katarzyna, AU - McDowell,Shana, AU - Mansouri,Katayoun, AU - Parks,Robert, AU - Stalls,Victoria, AU - Kopp,Megan F, AU - Manne,Kartik, AU - Li,Dapeng, AU - Wiehe,Kevin, AU - Saunders,Kevin O, AU - Edwards,Robert J, AU - Korber,Bette, AU - Haynes,Barton F, AU - Henderson,Rory, AU - Acharya,Priyamvada, Y1 - 2021/06/24/ PY - 2021/03/20/received PY - 2021/06/16/accepted PY - 2021/6/26/pubmed PY - 2021/8/14/medline PY - 2021/6/25/entrez JF - Science (New York, N.Y.) JO - Science VL - 373 IS - 6555 N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike mutations enable increased transmission and antibody resistance. We combined cryo-electron microscopy (cryo-EM), binding, and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans, and others that originated and spread in human populations. All variants showed increased angiotensin-converting enzyme 2 (ACE2) receptor binding and increased propensity for receptor binding domain (RBD)-up states. While adaptation to mink resulted in spike destabilization, the B.1.1.7 (UK) spike balanced stabilizing and destabilizing mutations. A local destabilizing effect of the RBD E484K mutation was implicated in resistance of the B.1.1.28/P.1 (Brazil) and B.1.351 (South Africa) variants to neutralizing antibodies. Our studies revealed allosteric effects of mutations and mechanistic differences that drive either interspecies transmission or escape from antibody neutralization. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/34168071/Effect_of_natural_mutations_of_SARS-CoV-2_on_spike_structure,_conformation,_and_antigenicity. DB - PRIME DP - Unbound Medicine ER -