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Distinctive Combinations of RBD Mutations Contribute to Antibody Evasion in the Case of the SARS-CoV-2 Beta Variant

  • Tae-Hun Kim (Korea Zoonosis Research Institute, Department of Bioactive Material Science and Genetic Engineering Research Institute, Jeonbuk National University) ;
  • Sojung Bae (Korea Zoonosis Research Institute, Department of Bioactive Material Science and Genetic Engineering Research Institute, Jeonbuk National University) ;
  • Sunggeun Goo (Korea Zoonosis Research Institute, Department of Bioactive Material Science and Genetic Engineering Research Institute, Jeonbuk National University) ;
  • Jinjong Myoung (Korea Zoonosis Research Institute, Department of Bioactive Material Science and Genetic Engineering Research Institute, Jeonbuk National University)
  • Received : 2023.08.14
  • Accepted : 2023.10.13
  • Published : 2023.12.28

Abstract

Since its first report in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a grave threat to public health. Virus-specific countermeasures, such as vaccines and therapeutics, have been developed and have contributed to the control of the viral pandemic, which has become endemic. Nonetheless, new variants continue to emerge and could cause a new pandemic. Consequently, it is important to comprehensively understand viral evolution and the roles of mutations in viral infectivity and transmission. SARS-CoV-2 beta variant encode mutations (D614G, N501Y, E484K, and K417N) in the spike which are frequently found in other variants as well. While their individual role in viral infectivity has been elucidated against various therapeutic antibodies, it still remains unclear whether those mutations may act additively or synergistically when combined. Here, we report that N501Y mutation shows differential effect on two therapeutic antibodies tested. Interestingly, the relative importance of E484K and K417N mutations in antibody evasion varies depending on the antibody type. Collectively, these findings suggest that continuous efforts to develop effective antibody therapeutics and combinatorial treatment with multiple antibodies are more rational and effective forms of treatment.

Keywords

Acknowledgement

The research was performed with the support by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2021M3E5E3080533). And we thank Dr. Kyu-Jin Park and Dr. Yeon-Sook Kim for their generous gifts of the antibodies used in this study.

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