Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody

Wang, X.; Lv, Z.; Deng, Y.-Q.; Ye, Q.; Cao, L.; Sun, C.-Y.; Fan, C.; Huang, W.; Sun, S.; Sun, Y.; Zhu, L.; Chen, Q.; Wang, N.; Nie, J.; Cui, Z.; Zhu, D.; Shaw, N.; Li, X.-F.; Li, Q.; Xie, L.; Wang, Y.; Rao, Z.; Qin, C.-F.

doi:10.1101/2020.06.02.129098

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bioRxiv · 10.1101/2020.06.02.129098

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody

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Abstract

The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in open conformation. Biochemical, cellular, virological and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19. One sentence summaryA potent neutralizing antibody conferred protection against SARS-CoV-2 in an hACE2 humanized mouse model by sterically blocking the interaction of the virus with its receptor.

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Wang, X., Lv, Z., Deng, Y.-Q., Ye, Q., Cao, L., Sun, C.-Y., Fan, C., Huang, W., Sun, S., Sun, Y., Zhu, L., Chen, Q., Wang, N., Nie, J., Cui, Z., Zhu, D., Shaw, N., Li, X.-F., Li, Q., Xie, L., Wang, Y., Rao, Z., Qin, C.-F.. 2020-06-02. Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody. https://doi.org/10.1101/2020.06.02.129098

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