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

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, Hanmi Noh, Geun-Soo Park, Jae Sang Park, Dain Son, Yongjin An, Jeong No Lee, Ki-Sung Kwon, Joo-Yeon Lee, Hansaem Lee, Jeong-Sun Yang, Kyung-Chang Kim, Sung Soon Kim, Hye-Min Woo, Jun-Won Kim, Man-Seong Park, Kwang-Min Yu, Se-Mi Kim, Eun-Ha Kim, Su-Jin Park, Seong Tae Jeong, Chi Ho Yu, Youngjo Song, Se Hun Gu, Hanseul Oh, Bon-Sang Koo, Jung Joo Hong, Choong-Min Ryu, Wan Beom Park, Myoung-don Oh, Young Ki Choi () and Soo-Young Lee ()
Additional contact information
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
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

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20602-5

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