Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity

Gobeil, Sophie M.C.; Janowska, Katarzyna; McDowell, Shana; Mansouri, Katayoun; Parks, Robert; Stalls, Victoria; Kopp, Megan F.; Manne, Kartik; Li, Dapeng; Wiehe, Kevin; Saunders, Kevin O.; Edwards, Robert J.; Korber, Bette Tina; Haynes, Barton F.; Henderson, Rory; Acharya, Priyamvada

doi:10.1126/science.abi6226

Title: Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity

Journal Article · 05 August 2021 · Science

DOI: https://doi.org/10.1126/science.abi6226 · OSTI ID:2000923

^[1]; Janowska, Katarzyna ^[1];

^[1]; Mansouri, Katayoun ^[1];

^[1];

^[1]; Kopp, Megan F. ^[1];

^[1]; Li, Dapeng ^[1];

^[2];

^[3];

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Duke University, Durham, NC (United States). Duke Human Vaccine Institute
Duke University, Durham, NC (United States).
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

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.

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Research Organization:: -Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 2000923

Report Number(s):: LA-UR--21-25180

Journal Information:: Science, Journal Name: Science Journal Issue: 6555 Vol. 373; ISSN 0036-8075

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

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