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

Li, Tingting; Han, Xiaojian; Gu, Chenjian; Guo, Hangtian; Zhang, Huajun; Wang, Yingming; Hu, Chao; Wang, Kai et al. · Nat Commun · 2021

basic_science · Level V

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Abstract

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<sup>470-495</sup> on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly binds to another region S<sup>450-458</sup> 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.

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