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

Abstract 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 receptor binding domain (RBD) of viral spike protein via antibody library constructed from peripheral blood mononuclear cells a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including D614G variant without antibody-dependent enhancement effect. Complex crystal structure Fab/RBD shows that blocks interaction regions RBD angiotensin converting enzyme (ACE2) with an orientation is notably different previously reported RBD-targeting mAbs. Furthermore, therapeutic effects evaluated in three animal models (ferret, hamster, rhesus monkey), demonstrating substantial reduction titer along alleviation clinical symptoms. Therefore, may be promising candidate COVID-19.