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A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein

Author

Listed:
  • Cheolmin Kim

    (Celltrion Inc)

  • Dong-Kyun Ryu

    (Celltrion Inc)

  • Jihun Lee

    (Celltrion Inc)

  • Young-Il Kim

    (Chungbuk National University)

  • Ji-Min Seo

    (Celltrion Inc)

  • Yeon-Gil Kim

    (Pohang University of Science and Technology)

  • Jae-Hee Jeong

    (Pohang University of Science and Technology)

  • Minsoo Kim

    (Celltrion Inc)

  • Jong-In Kim

    (Celltrion Inc)

  • Pankyeom Kim

    (Celltrion Inc)

  • Jin Soo Bae

    (Celltrion Inc)

  • Eun Yeong Shim

    (Celltrion Inc)

  • Min Seob Lee

    (Celltrion Inc)

  • Man Su Kim

    (Celltrion Inc)

  • Hanmi Noh

    (Celltrion Inc)

  • Geun-Soo Park

    (Celltrion Inc)

  • Jae Sang Park

    (Celltrion Inc)

  • Dain Son

    (Celltrion Inc)

  • Yongjin An

    (Celltrion Inc)

  • Jeong No Lee

    (Celltrion Inc)

  • Ki-Sung Kwon

    (Celltrion Inc)

  • Joo-Yeon Lee

    (Korea Centers for Disease Control and Prevention)

  • Hansaem Lee

    (Korea Centers for Disease Control and Prevention)

  • Jeong-Sun Yang

    (Korea Centers for Disease Control and Prevention)

  • Kyung-Chang Kim

    (Korea Centers for Disease Control and Prevention)

  • Sung Soon Kim

    (Korea Centers for Disease Control and Prevention)

  • Hye-Min Woo

    (Korea Centers for Disease Control and Prevention)

  • Jun-Won Kim

    (Korea Centers for Disease Control and Prevention)

  • Man-Seong Park

    (Korea University)

  • Kwang-Min Yu

    (Chungbuk National University)

  • Se-Mi Kim

    (Chungbuk National University)

  • Eun-Ha Kim

    (Chungbuk National University)

  • Su-Jin Park

    (Chungbuk National University
    Gyeongsang National University)

  • Seong Tae Jeong

    (Agency for Defense Development)

  • Chi Ho Yu

    (Agency for Defense Development)

  • Youngjo Song

    (Agency for Defense Development)

  • Se Hun Gu

    (Agency for Defense Development)

  • Hanseul Oh

    (Korea Research Institute of Bioscience and Biotechnology)

  • Bon-Sang Koo

    (Korea Research Institute of Bioscience and Biotechnology)

  • Jung Joo Hong

    (Korea Research Institute of Bioscience and Biotechnology)

  • Choong-Min Ryu

    (Korea Research Institute of Bioscience and Biotechnology)

  • Wan Beom Park

    (Seoul National University College of Medicine)

  • Myoung-don Oh

    (Seoul National University College of Medicine)

  • Young Ki Choi

    (Chungbuk National University)

  • Soo-Young Lee

    (Celltrion Inc)

Abstract

Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.

Suggested Citation

  • Cheolmin Kim & Dong-Kyun Ryu & Jihun Lee & Young-Il Kim & Ji-Min Seo & Yeon-Gil Kim & Jae-Hee Jeong & Minsoo Kim & Jong-In Kim & Pankyeom Kim & Jin Soo Bae & Eun Yeong Shim & Min Seob Lee & Man Su Kim, 2021. "A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20602-5
    DOI: 10.1038/s41467-020-20602-5
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    Cited by:

    1. Lei Peng & Yingxia Hu & Madeleine C. Mankowski & Ping Ren & Rita E. Chen & Jin Wei & Min Zhao & Tongqing Li & Therese Tripler & Lupeng Ye & Ryan D. Chow & Zhenhao Fang & Chunxiang Wu & Matthew B. Dong, 2022. "Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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