tetano
Editor, Senior Moderator
Nat Commun
. 2021 Jan 12;12(1):288.
doi: 10.1038/s41467-020-20602-5.
A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein
Cheolmin Kim[SUP] 1 [/SUP], Dong-Kyun Ryu[SUP] 1 [/SUP], Jihun Lee[SUP] 1 [/SUP], Young-Il Kim[SUP] 2 [/SUP], Ji-Min Seo[SUP] 1 [/SUP], Yeon-Gil Kim[SUP] 3 [/SUP], Jae-Hee Jeong[SUP] 3 [/SUP], Minsoo Kim[SUP] 1 [/SUP], Jong-In Kim[SUP] 1 [/SUP], Pankyeom Kim[SUP] 1 [/SUP], Jin Soo Bae[SUP] 1 [/SUP], Eun Yeong Shim[SUP] 1 [/SUP], Min Seob Lee[SUP] 1 [/SUP], Man Su Kim[SUP] 1 [/SUP], Hanmi Noh[SUP] 1 [/SUP], Geun-Soo Park[SUP] 1 [/SUP], Jae Sang Park[SUP] 1 [/SUP], Dain Son[SUP] 1 [/SUP], Yongjin An[SUP] 1 [/SUP], Jeong No Lee[SUP] 1 [/SUP], Ki-Sung Kwon[SUP] 1 [/SUP], Joo-Yeon Lee[SUP] 4 [/SUP], Hansaem Lee[SUP] 4 [/SUP], Jeong-Sun Yang[SUP] 4 [/SUP], Kyung-Chang Kim[SUP] 4 [/SUP], Sung Soon Kim[SUP] 4 [/SUP], Hye-Min Woo[SUP] 4 [/SUP], Jun-Won Kim[SUP] 4 [/SUP], Man-Seong Park[SUP] 5 [/SUP], Kwang-Min Yu[SUP] 2 [/SUP], Se-Mi Kim[SUP] 2 [/SUP], Eun-Ha Kim[SUP] 2 [/SUP], Su-Jin Park[SUP] 2 6 [/SUP], Seong Tae Jeong[SUP] 7 [/SUP], Chi Ho Yu[SUP] 7 [/SUP], Youngjo Song[SUP] 7 [/SUP], Se Hun Gu[SUP] 7 [/SUP], Hanseul Oh[SUP] 8 [/SUP], Bon-Sang Koo[SUP] 8 [/SUP], Jung Joo Hong[SUP] 8 [/SUP], Choong-Min Ryu[SUP] 9 [/SUP], Wan Beom Park[SUP] 10 [/SUP], Myoung-Don Oh[SUP] 10 [/SUP], Young Ki Choi[SUP] 11 [/SUP], Soo-Young Lee[SUP] 12 [/SUP]
Affiliations
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.
. 2021 Jan 12;12(1):288.
doi: 10.1038/s41467-020-20602-5.
A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein
Cheolmin Kim[SUP] 1 [/SUP], Dong-Kyun Ryu[SUP] 1 [/SUP], Jihun Lee[SUP] 1 [/SUP], Young-Il Kim[SUP] 2 [/SUP], Ji-Min Seo[SUP] 1 [/SUP], Yeon-Gil Kim[SUP] 3 [/SUP], Jae-Hee Jeong[SUP] 3 [/SUP], Minsoo Kim[SUP] 1 [/SUP], Jong-In Kim[SUP] 1 [/SUP], Pankyeom Kim[SUP] 1 [/SUP], Jin Soo Bae[SUP] 1 [/SUP], Eun Yeong Shim[SUP] 1 [/SUP], Min Seob Lee[SUP] 1 [/SUP], Man Su Kim[SUP] 1 [/SUP], Hanmi Noh[SUP] 1 [/SUP], Geun-Soo Park[SUP] 1 [/SUP], Jae Sang Park[SUP] 1 [/SUP], Dain Son[SUP] 1 [/SUP], Yongjin An[SUP] 1 [/SUP], Jeong No Lee[SUP] 1 [/SUP], Ki-Sung Kwon[SUP] 1 [/SUP], Joo-Yeon Lee[SUP] 4 [/SUP], Hansaem Lee[SUP] 4 [/SUP], Jeong-Sun Yang[SUP] 4 [/SUP], Kyung-Chang Kim[SUP] 4 [/SUP], Sung Soon Kim[SUP] 4 [/SUP], Hye-Min Woo[SUP] 4 [/SUP], Jun-Won Kim[SUP] 4 [/SUP], Man-Seong Park[SUP] 5 [/SUP], Kwang-Min Yu[SUP] 2 [/SUP], Se-Mi Kim[SUP] 2 [/SUP], Eun-Ha Kim[SUP] 2 [/SUP], Su-Jin Park[SUP] 2 6 [/SUP], Seong Tae Jeong[SUP] 7 [/SUP], Chi Ho Yu[SUP] 7 [/SUP], Youngjo Song[SUP] 7 [/SUP], Se Hun Gu[SUP] 7 [/SUP], Hanseul Oh[SUP] 8 [/SUP], Bon-Sang Koo[SUP] 8 [/SUP], Jung Joo Hong[SUP] 8 [/SUP], Choong-Min Ryu[SUP] 9 [/SUP], Wan Beom Park[SUP] 10 [/SUP], Myoung-Don Oh[SUP] 10 [/SUP], Young Ki Choi[SUP] 11 [/SUP], Soo-Young Lee[SUP] 12 [/SUP]
Affiliations
- PMID: 33436577
- DOI: 10.1038/s41467-020-20602-5
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.