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

Kim, C.; Ryu, D.-K.; Lee, J.; Kim, Y.-I.; Seo, J.-M.; Kim, Y.-G.; Jeong, J.-H.; Kim, M.; Kim, J.-I.; Kim, P.; Bae, J.S.; Shim, E.Y.; Lee, M.S.; Kim, M.S.; Noh, H.; Park, G.-S.; Park, J.S.; Son, D.; An, Y.; Lee, J.N.; Kwon, K.-S.; Lee, J.-Y.; Lee, H.; Yang, J.-S.; Kim, K.-C.; Kim, S.S.; Woo, H.-M.; Kim, J.-W.; Park, M.-S.; Yu, K.-M.; Kim, S.-M.; Kim, E.-H.; Park, S.-J.; Jeong, S.T.; Yu, C.H.; Song, Y.; Gu, S.H.; Oh, H.; Koo, B.-S.; Hong, J.J.; Ryu, C.-M.; Park, W.B.; Oh, M.-D.; Choi, Y.K.; Lee, S.-Y.

doi:10.1038/s41467-020-20602-5

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

Kim, C.;
Ryu, D.-K.;
Lee, J.;
Kim, Y.-I.;
Seo, J.-M.;
... Park, M.-S.;
외 39명

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초록

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, The Author(s).

키워드

human monoclonal antibody; immunoglobulin G; rbd protein; regdanvimab; remdesivir; unclassified drug; virus RNA; virus spike protein; vitronectin; ACE2 protein, human; coronavirus spike glycoprotein; monoclonal antibody; neutralizing antibody; protein binding; spike protein, SARS-CoV-2; virus antibody; adult; animal experiment; animal model; animal tissue; antibody library; Article; bacterium isolation; clinical assessment; clinical evaluation; controlled study; convalescence; coronavirus disease 2019; crystal structure; female; hamster; human; human cell; in vitro study; in vivo study; male; Mustela putorius furo; nonhuman; pandemic; peripheral blood mononuclear cell; protein domain; protein interaction; receptor binding; rhesus monkey; Severe acute respiratory syndrome coronavirus 2; stereospecificity; symptom; therapy effect; virus load; virus replication; animal; chemistry; Chlorocebus aethiops; disease model; drug effect; drug therapy; immunology; Fc receptor; Mesocricetus; molecular model; mononuclear cell; protein conformation; Vero cell line; Cricetinae; Macaca mulatta; Mustela; SARS coronavirus; Angiotensin-Converting Enzyme 2; Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Chlorocebus aethiops; COVID-19; Disease Models, Animal; Female; Ferrets; Humans; Leukocytes, Mononuclear; Macaca mulatta; Male; Mesocricetus; Models, Molecular; Protein Binding; Protein Conformation; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Vero Cells; angiotensin converting enzyme 2; ct p 59; d614g protein; fab protein

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

저자: Kim, C.; Ryu, D.-K.; Lee, J.; Kim, Y.-I.; Seo, J.-M.; Kim, Y.-G.; Jeong, J.-H.; Kim, M.; Kim, J.-I.; Kim, P.; Bae, J.S.; Shim, E.Y.; Lee, M.S.; Kim, M.S.; Noh, H.; Park, G.-S.; Park, J.S.; Son, D.; An, Y.; Lee, J.N.; Kwon, K.-S.; Lee, J.-Y.; Lee, H.; Yang, J.-S.; Kim, K.-C.; Kim, S.S.; Woo, H.-M.; Kim, J.-W.; Park, M.-S.; Yu, K.-M.; Kim, S.-M.; Kim, E.-H.; Park, S.-J.; Jeong, S.T.; Yu, C.H.; Song, Y.; Gu, S.H.; Oh, H.; Koo, B.-S.; Hong, J.J.; Ryu, C.-M.; Park, W.B.; Oh, M.-D.; Choi, Y.K.; Lee, S.-Y.

DOI: 10.1038/s41467-020-20602-5

발행일: 2021-01-12

유형: Article

저널명: Nature Communications

권: 12

호: 1