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

• Published in: Nature communications Vol. 12; no. 1; pp. 288 - 10
• Main Authors: Kim, Cheolmin, Ryu, Dong-Kyun, Lee, Jihun, Kim, Young-Il, Seo, Ji-Min, Kim, Yeon-Gil, Jeong, Jae-Hee, Kim, Minsoo, Kim, Jong-In, Kim, Pankyeom, Bae, Jin Soo, Shim, Eun Yeong, Lee, Min Seob, Kim, Man Su, Noh, Hanmi, Park, Geun-Soo, Park, Jae Sang, Son, Dain, An, Yongjin, Lee, Jeong No, Kwon, Ki-Sung, Lee, Joo-Yeon, Lee, Hansaem, Yang, Jeong-Sun, Kim, Kyung-Chang, Kim, Sung Soon, Woo, Hye-Min, Kim, Jun-Won, Park, Man-Seong, Yu, Kwang-Min, Kim, Se-Mi, Kim, Eun-Ha, Park, Su-Jin, Jeong, Seong Tae, Yu, Chi Ho, Song, Youngjo, Gu, Se Hun, Oh, Hanseul, Koo, Bon-Sang, Hong, Jung Joo, Ryu, Choong-Min, Park, Wan Beom, Oh, Myoung-don, Choi, Young Ki, Lee, Soo-Young
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.01.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 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
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-20602-5

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.