한빛사논문
Cheolmin Kim1,11, Dong-Kyun Ryu1,11, Jihun Lee1,11, Young-Il Kim2,11, Ji-Min Seo1, Yeon-Gil Kim3, Jae-Hee Jeong3, Minsoo Kim1, Jong-In Kim1, Pankyeom Kim1, Jin Soo Bae1, Eun Yeong Shim1, Min Seob Lee1, Man Su Kim1, Hanmi Noh1, Geun-Soo Park1, Jae Sang Park1, Dain Son1, Yongjin An1, Jeong No Lee1, Ki-Sung Kwon1, Joo-Yeon Lee4, Hansaem Lee4, Jeong-Sun Yang4, Kyung-Chang Kim4, Sung Soon Kim4, Hye-Min Woo4, Jun-Won Kim4, Man-Seong Park5, Kwang-Min Yu2, Se-Mi Kim2, Eun-Ha Kim2, Su-Jin Park2,10, Seong Tae Jeong6, Chi Ho Yu6, Youngjo Song6, Se Hun Gu6, Hanseul Oh7, Bon-Sang Koo7, Jung Joo Hong7, Choong-Min Ryu8, Wan Beom Park9, Myoung-don Oh9, Young Ki Choi2,* & Soo-Young Lee1,*
1Biotechnology Research Institute, Celltrion Inc, Incheon 22014, Republic of Korea.
2College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
3Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Korea.
4Center for Infectious Diseases Research, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea.
5Department of Microbiology and Institute for Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
6The 4th R&D Institute, Agency for Defense Development, Yuseong, P.O.Box 35, Daejeon 34186, Republic of Korea.
7National Primate Research Centre, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea.
8Infectious Disease Research Centre, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
9Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
10Present address: Division of Applied Life Science and Research Institute of Life Sciences, Gyeongsang National University, Jinju 52828, Korea.
11These authors contributed equally: Cheolmin Kim, Dong-Kyun Ryu, Jihun Lee, Young-Il Kim.
*Corresponding author
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.
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