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Research Square | Vol., Issue. | 2020-09-09 | Pages

Research Square

A Novel Neutralizing Antibody Targeting Receptor Binding Domain of SARS-CoV-2

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

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current COVID-19 global pandemic. Vaccines and therapeutics are urgently needed for this highly transmissible virus. In this study, we screened human monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of the SARS-CoV-2 spike protein from an antibody library constructed from peripheral blood mononuclear cells of a COVID-19 convalescent patient. A potent neutralizing antibody, termed CT-P59, was identified and found to be effective against various SARS-CoV-2 isolates including the D614G spike protein variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/SARS-CoV-2 RBD showed that CT-P59 blocks interaction regions of SARS-CoV-2 RBD for its cellular receptor, angiotensin converting enzyme 2 (ACE2). The binding orientation of CT-P59 is notably different from the previously reported neutralizing mAbs targeting SARS-CoV-2 RBD suggesting that CT-P59 can be a novel binder to SARS-CoV-2 RBD. Therapeutic effects of CT-P59 were evaluated in three animal models (ferret, hamster, and rhesus monkey), and a substantial reduction in viral titre along with alleviation of clinical symptoms was observed. These findings suggest that the human monoclonal antibody, CT-P59, is a promising therapeutic candidate for treatment of COVID-19.

Original Text (This is the original text for your reference.)

A Novel Neutralizing Antibody Targeting Receptor Binding Domain of SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current COVID-19 global pandemic. Vaccines and therapeutics are urgently needed for this highly transmissible virus. In this study, we screened human monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of the SARS-CoV-2 spike protein from an antibody library constructed from peripheral blood mononuclear cells of a COVID-19 convalescent patient. A potent neutralizing antibody, termed CT-P59, was identified and found to be effective against various SARS-CoV-2 isolates including the D614G spike protein variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/SARS-CoV-2 RBD showed that CT-P59 blocks interaction regions of SARS-CoV-2 RBD for its cellular receptor, angiotensin converting enzyme 2 (ACE2). The binding orientation of CT-P59 is notably different from the previously reported neutralizing mAbs targeting SARS-CoV-2 RBD suggesting that CT-P59 can be a novel binder to SARS-CoV-2 RBD. Therapeutic effects of CT-P59 were evaluated in three animal models (ferret, hamster, and rhesus monkey), and a substantial reduction in viral titre along with alleviation of clinical symptoms was observed. These findings suggest that the human monoclonal antibody, CT-P59, is a promising therapeutic candidate for treatment of COVID-19.

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Koo, Bon-Sang, Kim, Kyung-Chang, Kim, Jun-Won, Gu, Se Hun, Park, Wan Beom, Noh, Hanmi, Hong, Jung Joo, Yu, Kwang-Min, Lee, Min Seob, Yu, Chi Ho, Jeong, Seong Tae, Kim, Jong-In, An, Yongjin, Bae, Jin Soo, Park, Man-Seong, Kim, Minsoo, Kwon, Ki-Sung, Ryu, Choong-Min, Seo, Ji-Min, Park, Geun-Soo, Lee, Hansaem, Park, Su-Jin, Oh, Myoung-don, Son, Dain, Shim, Eun Yeong, Song, Youngjo, Kim, Cheolmin, Jeong, Jae-Hee, Kim, Sung Soon, Kim, Pankyeom, Lee, Joo-Yeon, Choi, Young Ki, Ryu, Dong-Kyun, Park, Jae Sang, Kim, Young-Il, Lee, Jeong No, Yang, Jeong-Sun, Woo, Hye-Min, Lee, Jihun, Kim, Se-Mi,Lee, Soo-Young, Oh, Hanseul, Kim, Man Su, kim, Yeon-Gil, Kim, Eun-Ha,.A Novel Neutralizing Antibody Targeting Receptor Binding Domain of SARS-CoV-2. (),.

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