Structural insights for neutralization of Omicron variants BA.1, BA.2, BA.4, and BA.5 by a broadly neutralizing SARS-CoV-2 antibody

• Published in: Science advances Vol. 8; no. 40; p. eadd2032
• Main Authors: Kumar, Sanjeev, Patel, Anamika, Lai, Lilin, Chakravarthy, Chennareddy, Valanparambil, Rajesh, Reddy, Elluri Seetharami, Gottimukkala, Kamalvishnu, Davis-Gardner, Meredith E., Edara, Venkata Viswanadh, Linderman, Susanne, Nayak, Kaustuv, Dixit, Kritika, Sharma, Pragati, Bajpai, Prashant, Singh, Vanshika, Frank, Filipp, Cheedarla, Narayanaiah, Verkerke, Hans P., Neish, Andrew S., Roback, John D., Mantus, Grace, Goel, Pawan Kumar, Rahi, Manju, Davis, Carl W., Wrammert, Jens, Godbole, Sucheta, Henry, Amy R., Douek, Daniel C., Suthar, Mehul S., Ahmed, Rafi, Ortlund, Eric, Sharma, Amit, Murali-Krishna, Kaja, Chandele, Anmol
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 07.10.2022
• Subjects: Angiotensin-Converting Enzyme 2; Antibodies, Monoclonal - chemistry; Antibodies, Viral; Biomedicine and Life Sciences; Coronavirus; COVID-19; Epitopes; Humans; Neutralization Tests; SARS-CoV-2 - genetics; SciAdv r-articles; Spike Glycoprotein, Coronavirus
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.add2032

In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19–recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)–specific mAb 002-S21F2 that has rare gene usage and potently neutralized live viral isolates of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron sublineages (BA.1, BA.2, BA.2.12.1, BA.4, and BA.5) with IC 50 ranging from 0.02 to 0.13 μg/ml. Structural studies of 002-S21F2 in complex with spike trimers of Omicron and WA.1 showed that it targets a conformationally conserved epitope on the outer face of RBD (class 3 surface) outside the ACE2-binding motif, thereby providing a mechanistic insights for its broad neutralization activity. The discovery of 002-S21F2 and the broadly neutralizing epitope it targets have timely implications for developing a broad range of therapeutic and vaccine interventions against SARS-CoV-2 variants including Omicron sublineages. A rare human monoclonal antibody neutralizes all SARS-CoV-2 Omicron variants by targeting a conserved epitope on the RBD.