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

• Published in: Nature communications 2021-11, Vol.12 (1), p.6304-6304, Article 6304
• Main Authors: Li, Tingting, Han, Xiaojian, Gu, Chenjian, Guo, Hangtian, Zhang, Huajun, Wang, Yingming, Hu, Chao, Wang, Kai, Liu, Fengjiang, Luo, Feiyang, Zhang, Yanan, Hu, Jie, Wang, Wang, Li, Shenglong, Hao, Yanan, Shen, Meiying, Huang, Jingjing, Long, Yingyi, Song, Shuyi, Wu, Ruixin, Mu, Song, Chen, Qian, Gao, Fengxia, Wang, Jianwei, Long, Shunhua, Li, Luo, Wu, Yang, Gao, Yan, Xu, Wei, Cai, Xia, Qu, Di, Zhang, Zherui, Zhang, Hongqing, Li, Na, Gao, Qingzhu, Zhang, Guiji, He, Changlong, Wang, Wei, Ji, Xiaoyun, Tang, Ni, Yuan, Zhenghong, Xie, Youhua, Yang, Haitao, Zhang, Bo, Huang, Ailong, Jin, Aishun
• Format: Article
• Language: English
• Subjects: 101/28; 13/1; 13/109; 631/250/2152/2153/1291; 631/326/596/4130; 64/110; 82/1; 82/103; 82/29; 82/83; ACE2; Angiotensin-converting enzyme 2; Binding; Coronaviruses; COVID-19; Humanities and Social Sciences; Infections; Monoclonal antibodies; multidisciplinary; Mutation; Neutralizing; Pandemics; Prophylaxis; Receptors; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Structural analysis; Transgenic mice; Viral diseases; Viruses; Weight loss; Weight reduction
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26539-7

Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, 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 13G9 both recognize the steric region S 470–495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly binds to another region S 450–458 in the RBD. Significantly, 58G6 and 510A5 both demonstrate prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses 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. Neutralizing antibodies are currently one versatile strategy to treat SARS-CoV-2 infection. Here, Li et al. characterize three monoclonal antibodies neutralizing authentic virus infection in vitro and in vivo by targeting the receptor binding domain as evidenced by Cryo-EM.