Research Square | Vol., Issue. | 2020-09-09 | Pages
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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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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covid19 convalescent cellular receptor angiotensin converting enzyme viral titre antibodies receptor binding domain rbd sarscov2 spike protein antibody ctp59 respiratory syndrome antibodydependent enhancement
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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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