This study reports the isolation and characterization of two human monoclonal antibodies, CA1 and CB6, which specifically recognize the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Both antibodies demonstrated potent neutralizing activity against SARS-CoV-2 in vitro and in a rhesus macaque model of infection. Structural analysis revealed that CB6 recognizes an epitope that overlaps with the angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 RBD, interfering with virus-receptor interactions through steric hindrance and direct competition. The study suggests that CB6 is a promising candidate for clinical translation as a therapeutic agent against COVID-19.This study reports the isolation and characterization of two human monoclonal antibodies, CA1 and CB6, which specifically recognize the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Both antibodies demonstrated potent neutralizing activity against SARS-CoV-2 in vitro and in a rhesus macaque model of infection. Structural analysis revealed that CB6 recognizes an epitope that overlaps with the angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 RBD, interfering with virus-receptor interactions through steric hindrance and direct competition. The study suggests that CB6 is a promising candidate for clinical translation as a therapeutic agent against COVID-19.