Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape. This study identifies three receptor-binding domain (RBD)-specific monoclonal antibodies (mAbs), 58G6, 510A5, and 1369, with high neutralizing potency against authentic SARS-CoV-2 and the B.1.351 variant. Structural analysis reveals that 58G6 and 1369 recognize overlapping regions on the RBD, including the E484K mutation. 58G6 and 510A5 demonstrate prophylactic efficacy in hACE2 transgenic mice, protecting against weight loss and reducing viral loads. These potent neutralizing antibodies offer promising candidates for COVID-19 treatment.

Tingting Li, Xiaojin Han, Chenjian Gu, Hangtian Guo, Huajun Zhang, Yingming Wang, Chao Hu, Kai Wang, Fengjiang Liu, Feiyang Luo, Yanan Zhang, Jie Hu, Wang Wang, Shenglong Li, Yanan Hao, Meiying Shen, Jingjing Huang, Yingyi Long, Shuyi Song, Ruixin Wu, Song Mu, Qian Chen, Fengxia Gao, Jianwei Wang, Shunhua Long, Luo Li, Yang Wu, Yan Gao, Wei Xu, Xia Cai, Di Qu, Zherui Zhang, Hongqing Zhang, Na Li, Qingzhu Gao, Guiji Zhang, Changlong He, Wei Wang, Xiaoyun Ji, Ni Tang, Zhenghong Yuan, Youhua Xie, Haitao Yang, Bo Zhang, Ailong Huang, Aishun Jin