A human monoclonal antibody potently pan-neutralizes SARS-CoV-2 VOCs by targeting RBD invariant sites

Wang, X.; Hu, A.; Chen, X.; Zhang, Y.; Yu, F.; Yue, S.; Li, A.; Zhang, J.; Pan, Z.; Yang, Y.; Lin, Y.; Gao, L.; Zhou, J.; Zhao, J.; Li, F.; Shi, Y.; Huang, F.; Yang, X.; Peng, Y.; Tu, L.; Zhang, H.; Zheng, H.; He, J.; Xu, L.; Huang, Q.; Zhu, Y.; Deng, K.; Ye, L.

doi:10.1101/2021.11.29.470356

bioRxiv · 10.1101/2021.11.29.470356

A human monoclonal antibody potently pan-neutralizes SARS-CoV-2 VOCs by targeting RBD invariant sites

Wang, X.·Hu, A.·Chen, X.·Zhang, Y.·Yu, F.·Yue, S.·Li, A.·Zhang, J.·Pan, Z.·Yang, Y.·Lin, Y.·Gao, L.·Zhou, J.·Zhao, J.·Li, F.·Shi, Y.·Huang, F.·Yang, X.·Peng, Y.·Tu, L.·Zhang, H.·Zheng, H.·He, J.·Xu, L.·Huang, Q.·Zhu, Y.·Deng, K.·Ye, L.

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Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.

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Wang, X., Hu, A., Chen, X., Zhang, Y., Yu, F., Yue, S., Li, A., Zhang, J., Pan, Z., Yang, Y., Lin, Y., Gao, L., Zhou, J., Zhao, J., Li, F., Shi, Y., Huang, F., Yang, X., Peng, Y., Tu, L., Zhang, H., Zheng, H., He, J., Xu, L., Huang, Q., Zhu, Y., Deng, K., Ye, L.. 2021-11-30. A human monoclonal antibody potently pan-neutralizes SARS-CoV-2 VOCs by targeting RBD invariant sites. https://doi.org/10.1101/2021.11.29.470356

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