Here, in our study, we first reported that OA has abilities to directly bind Delta (B.1.617.2) and Omicron (B.1.1.529) RBD as well as ACE2, by which it effectively blocked SARS-CoV-2 variant entry to cells and may be considered as an anti-SARS-CoV-2 candidate for COVID-19 drug development. Here, ACE2 is linked to COVID-19.