Journal Article

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

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

2021

Overview

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. Therapies and vaccines for COVID-19, caused by the SARS-CoV-2 viral pandemic, are urgently needed. Here the authors establish and screen an antibody library from a convalescent COVID-19 patient to isolate a neutralizing antibody with the ability to reduce viral titer and alleviate symptoms in ferret, hamster, and rhesus monkey infection models.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 101/1 / 13/1 / 13/106 / 49/1 / 631/250/2152/2153/1291 / 631/250/255/2514 / 631/326/596/4130 / 631/61/51/1568 / 82/103 / ACE2 / Angiotensin / Angiotensin-converting enzyme 2 / Angiotensin-Converting Enzyme 2 - chemistry / Animal models / Animals / Antibodies / Antibodies, Monoclonal - immunology / Antibodies, Neutralizing - chemistry / Antibodies, Neutralizing - immunology / Antibodies, Neutralizing - pharmacology / Antibodies, Viral - immunology / Antibody libraries / Binding / Chlorocebus aethiops / Coronaviruses / COVID-19 / COVID-19 - drug therapy / Crystal structure / Disease Models, Animal / Domains / Female / Ferrets / Humanities and Social Sciences / Humans / Leukocytes, Mononuclear / Libraries / Macaca mulatta / Male / Mesocricetus / Models, Molecular / Monkeys & apes / Monoclonal antibodies / multidisciplinary / Neutralizing / Pandemics / Peptidyl-dipeptidase A / Peripheral blood mononuclear cells / Protein Binding - drug effects / Protein Conformation / Proteins / Receptors / SARS-CoV-2 - drug effects / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - chemistry / Spike Glycoprotein, Coronavirus - drug effects / Spike protein / Vaccines / Vero Cells / Viral diseases