| Autor: |
Sanjeev Kumar, Anamika Patel, Lilin Lai, Chennareddy Chakravarthy, Rajesh Valanparambil, Meredith E. Davis-Gardner, Venkata Viswanadh Edara, Susanne Linderman, Elluri Seetharami Reddy, Kamalvishnu Gottimukkala, Kaustuv Nayak, Prashant Bajpai, Vanshika Singh, Filipp Frank, Narayanaiah Cheedarla, Hans P. Verkerke, Andrew S. Neish, John D. Roback, Grace Mantus, Pawan Kumar Goel, Manju Rahi, Carl W. Davis, Jens Wrammert, Mehul S. Suthar, Rafi Ahmed, Eric Ortlund, Amit Sharma, Kaja Murali-Krishna, Anmol Chandele |
| Rok vydání: |
2022 |
| Popis: |
The SARS-CoV-2 BA.1 and BA.2 (Omicron) variants contain more than 30 mutations within the spike protein and evade therapeutic monoclonal antibodies (mAbs). Here, we report a receptor-binding domain (RBD) targeting human antibody (002-S21F2) that effectively neutralizes live viral isolates of SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron (BA.1 and BA.2) with IC50 ranging from 0.02 – 0.05 μg/ml. This near germline antibody 002-S21F2 has unique genetic features that are distinct from any reported SARS-CoV-2 mAbs. Structural studies of the full-length IgG in complex with spike trimers (Omicron and WA.1) reveal that 002-S21F2 recognizes an epitope on the outer face of RBD (class-3 surface), outside the ACE2 binding motif and its unique molecular features enable it to overcome mutations found in the Omicron variants. The discovery and comprehensive structural analysis of 002-S21F2 provide valuable insight for broad and potent neutralization of SARS-CoV-2 Omicron variants BA.1 and BA.2. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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