SARS-CoV-2 variants with multiple spike mutations enable increased transmission and antibody resistance. In this article the authors combine 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 ACE2 receptor binding and increased propensity for 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. The authors concluded that their studies revealed allosteric effects of mutations and mechanistic differences that drive either inter-species transmission or escape from antibody neutralization.
Gobeil SM, 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. Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity. Science. 2021 Jun 24:eabi6226. doi: 10.1126/science.abi6226.