Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Gobeil, SM-C; Janowska, K; McDowell, S; Mansouri, K; Parks, R; Stalls, V; Kopp, MF; Manne, K; Li, D; Wiehe, K; Saunders, KO; Edwards, RJ; Korber, B; Haynes, BF; Henderson, R; Acharya, P
Published Date
- August 6, 2021
Published In
Volume / Issue
- 373 / 6555
PubMed ID
- 34168071
Pubmed Central ID
- PMC8611377
Electronic International Standard Serial Number (EISSN)
- 1095-9203
Digital Object Identifier (DOI)
- 10.1126/science.abi6226
Language
- eng
Conference Location
- United States