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

Kim, Cheolmin; Ryu, Dong-Kyun; Lee, Jihun; Kim, Young-Il; Seo, Ji-Min; Kim, Yeon-Gil; Jeong, Jae-Hee; Kim, Minsoo; Kim, Jong-In; Kim, Pankyeom; Bae, Jin Soo; Shim, Eun Yeong; Lee, Min Seob; Kim, Man Su; Noh, Hanmi; Park, Geun-Soo; Park, Jae Sang; Son, Dain; An, Yongjin; Lee, Jeong No; Kwon, Ki-Sung; Lee, Joo-Yeon; Lee, Hansaem; Yang, Jeong-Sun; Kim, Kyung-Chang; Kim, Sung Soon; Woo, Hye-Min; Kim, Jun-Won; Park, Man-Seong; Yu, Kwang-Min; Kim, Se-Mi; Kim, Eun-Ha; Park, Su-Jin; Jeong, Seong Tae; Yu, Chi Ho; Song, Youngjo; Gu, Se Hun; Oh, Hanseul; Koo, Bon-Sang; Hong, Jung Joo; Ryu, Choong-Min; Park, Wan Beom; Oh, Myoung-don; Choi, Young Ki; Lee, Soo-Young

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.