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

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.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, COVID-19 Drug Treatment, Chlorocebus aethiops, 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
Nat Commun
Date: Jan. 12, 2021
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