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 == Publication Abstract from PubMed ==
-New SARS-CoV-2 variants that have accumulated multiple mutations in the spike (S) glycoprotein enable increased transmission and resistance to neutralizing antibodies. Here, we study the antigenic and structural impacts of the S protein mutations from four variants, one that was involved in transmission between minks and humans, and three that rapidly spread in human populations and originated in the United Kingdom, Brazil or South Africa. All variants either retained or improved binding to the ACE2 receptor. The B.1.1.7 (UK) and B.1.1.28 (Brazil) spike variants showed reduced binding to neutralizing NTD and RBD antibodies, respectively, while the B.1.351 (SA) variant showed reduced binding to both NTD- and RBD-directed antibodies. Cryo-EM structural analyses revealed allosteric effects of the mutations on spike conformations and revealed mechanistic differences that either drive inter-species transmission or promotes viral escape from dominant neutralizing epitopes. Highlights: Cryo-EM structures reveal changes in SARS-CoV-2 S protein during inter-species transmission or immune evasion.Adaptation to mink resulted in increased ACE2 binding and spike destabilization.B.1.1.7 S mutations reveal an intricate balance of stabilizing and destabilizing effects that impact receptor and antibody binding.E484K mutation in B.1.351 and B.1.1.28 S proteins drives immune evasion by altering RBD conformation.S protein uses different mechanisms to converge upon similar solutions for altering RBD up/down positioning.
+SARS-CoV-2 variants with multiple spike mutations enable increased transmission and antibody resistance. Here, we 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. Our studies revealed allosteric effects of mutations and mechanistic differences that drive either inter-species transmission or escape from antibody neutralization.
-Effect of natural mutations of SARS-CoV-2 on spike structure, conformation and antigenicity.,Gobeil SM, Janowska K, McDowell S, Mansouri K, Parks R, Stalls V, Kopp MF, Manne K, Saunders K, Edwards RJ, Haynes BF, Henderson RC, Acharya P bioRxiv. 2021 Mar 15. doi: 10.1101/2021.03.11.435037. PMID:33758838<ref>PMID:33758838</ref>
+Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity.,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 Science. 2021 Jun 24. pii: science.abi6226. doi: 10.1126/science.abi6226. PMID:34168071<ref>PMID:34168071</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>