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 LeeKi 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, Soo Young Lee

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Article number288
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021

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