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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 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. 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.
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1 Chongqing Medical University, Department of Immunology, College of Basic Medicine, Chongqing, China (GRID:grid.203458.8) (ISNI:0000 0000 8653 0555); Chongqing Medical University, Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing, China (GRID:grid.203458.8) (ISNI:0000 0000 8653 0555)
2 Fudan University, Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443)
3 ShanghaiTech University, Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, Shanghai, China (GRID:grid.440637.2) (ISNI:0000 0004 4657 8879); Nanjing University, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing, China (GRID:grid.41156.37) (ISNI:0000 0001 2314 964X)
4 Chinese Academy of Sciences, State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Wuhan, China (GRID:grid.9227.e) (ISNI:0000000119573309)
5 Chongqing Medical University, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing, China (GRID:grid.203458.8) (ISNI:0000 0000 8653 0555)
6 ShanghaiTech University, Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, Shanghai, China (GRID:grid.440637.2) (ISNI:0000 0004 4657 8879)
7 Chinese Academy of Sciences, Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Wuhan, China (GRID:grid.9227.e) (ISNI:0000000119573309); University of Chinese Academy of Sciences, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419)
8 Harbin Medical University Cancer Hospital, Department of Breast Surgery, Harbin, China (GRID:grid.412651.5) (ISNI:0000 0004 1808 3502)
9 Chongqing Medical University, Institute of life sciences, Chongqing, China (GRID:grid.203458.8) (ISNI:0000 0000 8653 0555)
10 Nanjing University, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing, China (GRID:grid.41156.37) (ISNI:0000 0001 2314 964X); Chongqing Medical University, Institute of life sciences, Chongqing, China (GRID:grid.203458.8) (ISNI:0000 0000 8653 0555)
11 Chinese Academy of Sciences, Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Wuhan, China (GRID:grid.9227.e) (ISNI:0000000119573309)