Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants

Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, highlighting the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 1369, with high neutralizing potency blocking authentic SARS-CoV-2 virus display remarkable efficacy against authentic B.1.351 virus. Surprisingly, structural analysis has revealed that 58G6 and 1369 both recognize the steric region S470–495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly binds to another region S450–458 in the RBD. Additionally, 58G6 and 510A5 both demonstrate prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 virus in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. Together, we have evidenced 2 potent neutralizing Abs with unique mechanism targeting authentic SARS-CoV-2 mutants, which can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.

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