biostudies-literatureUnknown31(11)Sun CPThe ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evadinMolecular therapy : the journal of the American Society of Gene Therapy3322-3336https://www.ebi.ac.uk/biostudies/studies/S-EPMC10638075biostudies-literatureDevelopment of AAV-delivered broadly neutralizing anti-human ACE2 antibodies against SARS-CoV-2 variants.PMC10638075Chang CSNg HYChen LYLiao CCKuo TJChung MJDanny Hsu STWu PYTsung SITseng SCLiu WCTao MHWu HCLo CHSun CPDraczkowski PPuri SHsu MFLiang JJChen CCHu CWLiao HNHuang JSLan YHChang YCChiu CWKau JHLee IJChen YJChen YHWang IHfalseDevelopment of AAV-delivered broadly neutralizing anti-human ACE2 antibodies against SARS-CoV-2 variants.The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evadin2023-01-01T00:00:00Z2023 Nov2026-06-02T23:10:31.942Z2025-04-04T00:26:31.41ZS-EPMC106380753768997110.1016/j.ymthe.2023.09.002