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

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 distinct 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.

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, Hanmin 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, Youngjoo Song, Se Hun Gu, Hanseul Oh, Bon-Sang Koo, Jung Joo Hong, Choong-Min Ryu, Wan Beom Park, Myoung-don Oh, Young Ki Choi, Soo-Young Lee