National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering (NIH/NIBIB)
3U54EB027690-04S
United States
Citation
Journal: Sci Adv / Year: 2022 Title: Structural insights for neutralization of Omicron variants BA.1, BA.2, BA.4, and BA.5 by a broadly neutralizing SARS-CoV-2 antibody. Authors: Sanjeev Kumar / Anamika Patel / Lilin Lai / Chennareddy Chakravarthy / Rajesh Valanparambil / Elluri Seetharami Reddy / Kamalvishnu Gottimukkala / Meredith E Davis-Gardner / Venkata ...Authors: Sanjeev Kumar / Anamika Patel / Lilin Lai / Chennareddy Chakravarthy / Rajesh Valanparambil / Elluri Seetharami Reddy / Kamalvishnu Gottimukkala / Meredith E Davis-Gardner / Venkata Viswanadh Edara / Susanne Linderman / Kaustuv Nayak / Kritika Dixit / Pragati Sharma / 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 / Sucheta Godbole / Amy R Henry / Daniel C Douek / Mehul S Suthar / Rafi Ahmed / Eric Ortlund / Amit Sharma / Kaja Murali-Krishna / Anmol Chandele / Abstract: 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) ...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 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.
Model: C-flat-1.2/1.3 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Pretreatment - Atmosphere: AIR
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 297 K / Instrument: FEI VITROBOT MARK IV / Details: Wait time 20 seconds and blot time 3 seconds.
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Electron microscopy
Microscope
FEI TALOS ARCTICA
Image recording
Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 2 / Number real images: 4553 / Average electron dose: 51.0 e/Å2
Electron beam
Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
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