A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein
2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês
10.1038/s41467-020-20602-5
ISSN2041-1723
AutoresCheol-Min Kim, Dong-Kyun Ryu, Jihun Lee, Young‐Il Kim, Ji Min Seo, Yeon‐Gil Kim, Jae-Hee Jeong, Min Soo 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, Young‐Jo 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,
Tópico(s)SARS-CoV-2 detection and testing
ResumoAbstract 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.
Referência(s)