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. Therapies and vaccines for COVID-19, caused by the SARS-CoV-2 viral pandemic, are urgently needed. Here the authors establish and screen an antibody library from a convalescent COVID-19 patient to isolate a neutralizing antibody with the ability to reduce viral titer and alleviate symptoms in ferret, hamster, and rhesus monkey infection models.
【저자키워드】 antibodies, SARS-CoV-2, viral infection, Antibody therapy, 【초록키워드】 COVID-19, neutralizing antibody, ACE2, Vaccine, coronavirus, pandemic, Clinical symptoms, antibody, Antibody-dependent enhancement, Therapeutics, Infection, animal model, Symptom, severe acute respiratory syndrome Coronavirus, angiotensin converting enzyme, Spike protein, Receptor binding domain, Peripheral blood, Region, Viral, RBD, D614G variant, Human monoclonal antibody, therapeutic, Peripheral blood mononuclear cells, receptor, hamster, respiratory, convalescent, crystal structure, mAbs, convalescent patient, mAb, human monoclonal antibodies, Interaction, angiotensin, COVID-19 patient, mononuclear cells, mononuclear cell, Orientation, viral spike protein, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, enzyme, therapeutic effects, therapeutic effect, SARS-CoV-2 isolates, rhesus, alleviation, viral titer, Complex crystal structure, block, neutralize, caused, reported, evaluated, reduce, reduction in, alleviate, SARS-CoV-2 isolate, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2 spike protein, therapeutic,