7tb4 | pdb_00007tb4
Cryo-EM structure of the spike of SARS-CoV-2 Omicron variant of concern
Structural highlights
Publication Abstract from PubMedThe emergence of highly transmissible SARS-CoV-2 variants of concern (VOC) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identify four receptor-binding domain targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 12 variants including the B.1.1.7 and B.1.351 VOCs. Two of them are ultrapotent, with sub-nanomolar neutralization titers (IC50 <0.0006 to 0.0102 mu g/mL; IC80 < 0.0006 to 0.0251 mu g/mL). We define the structural and functional determinants of binding for all four VOC-targeting antibodies, and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting potential means to mitigate resistance development. These results define the basis of therapeutic cocktails against VOCs and suggest that targeted boosting of existing immunity may increase vaccine breadth against VOCs. Antibodies with potent and broad neutralizing activity against antigenically diverse and highly transmissible SARS-CoV-2 variants.,Wang L, Zhou T, Zhang Y, Yang ES, Schramm CA, Shi W, Pegu A, Oloninyi OK, Ransier A, Darko S, Narpala SR, Hatcher C, Martinez DR, Tsybovsky Y, Phung E, Abiona OM, Cale EM, Chang LA, Corbett KS, DiPiazza AT, Gordon IJ, Leung K, Liu T, Mason RD, Nazzari A, Novik L, Olia AS, Doria-Rose NA, Stephens T, Stringham CD, Talana CA, Teng IT, Wagner D, Widge AT, Zhang B, Roederer M, Ledgerwood JE, Ruckwardt TJ, Gaudinski MR, Baric RS, Graham BS, McDermott AB, Douek DC, Kwong PD, Mascola JR, Sullivan NJ, Misasi J bioRxiv. 2021 Mar 1. doi: 10.1101/2021.02.25.432969. PMID:33655252[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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