Cross-reaction of current available SARS-CoV-2 MAbs against the pangolin-origin coronavirus GX/P2V/2017.

Yunfei Jia1,2 Sheng Niu3 Yu Hu4,5 Yan Chai2 Anqi Zheng4,6 Chao Su4,7 Lili Wu2 Pengcheng Han4,8 Pu Han2 Dan Lu4,9 Zhimin Liu3 Xinxin Yan1,2 Di Tian10 Zhihai Chen10 Jianxun Qi2 Wen-Xia Tian11 Qihui Wang1,4,12 George Fu Gao1,4,13
Affiliations 13 institutions
  1. College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China
  2. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  3. College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China.
  4. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
  5. School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
  6. University of the Chinese Academy of Sciences, Beijing 100049, China.
  7. Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR 999077, China.
  8. School of Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China.
  9. Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China.
  10. Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
  11. College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China. Electronic address: [email protected].
  12. Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
  13. Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].

Abstract

Since the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, multiple SARS-CoV-2-related viruses have been characterized, including pangolin-origin GD/1/2019 and GX/P2V/2017. Our previous study indicated that both viruses have the potential to infect humans. Here, we find that CB6 (commercial name etesevimab), a COVID-19 therapeutic monoclonal antibody (MAb) developed by our group, efficiently inhibits GD/1/2019 but not GX/P2V/2017. A total of 50 SARS-CoV-2 MAbs divided into seven groups based on their receptor-binding domain (RBD) epitopes, together with the COVID-19 convalescent sera, are systematically screened for their cross-binding and cross-neutralizing properties against GX/P2V/2017. We find that GX/P2V/2017 displays substantial immune difference from SARS-CoV-2. Furthermore, we solve two complex structures of the GX/P2V/2017 RBD with MAbs belonging to RBD-1 and RBD-5, providing a structural basis for their different antigenicity. These results highlight the necessity for broad anti-coronavirus countermeasures and shed light on potential therapeutic targets.

CP: Immunology 1 CP: Microbiology 7 immune difference 0 monoclonal antibody 2 pangolin CoVs 0 SARS-CoV-2 550 COVID-19 425 SARS-CoV-2 453 Antibodies, Monoclonal 26 Antibodies, Neutralizing 80 Antibodies, Viral 212 Humans 1440 Pangolins 29 Spike Glycoprotein, Coronavirus 274 spike protein, SARS-CoV-2 157

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