Bergenia purpurascens is a non-specific ACE2 inhibitor

Abstract Introduction Bergenia purpurascens is a medicinal herb found in southwestern China. This article mainly explores its efficacy and mechanism in blocking ACE2 receptor. Materials and methods This study investigated the ability of water extract of Bergenia purpurascens to disrupt the formation of the complex between COVID-19 S1 RBD and ACE2. After establishing quality standards for the extract, it was shown to inhibit live virus infection of COVID-19 XBB1.5 variant using a Vero-E6 cell infection model. The mechanism by which the water extract disrupts the binding of S1 protein and ACE2 was studied using SPR. The composition of the extract was analyzed using UPLC-MS/MS, and active compounds were identified through in silico screening and real activity testing. Results The water extracts of Bergenia purpurascens exhibit significantly high inhibitory activity and are found to be stable. The prominent compounds constituting the extract are Phenylpropanoids and Carbohydrates, whose abundance accounts for over 60% of the composition. The extract is highly potent in inhibiting live COVID-19 XBB1.5 virus infection, having an IC50 value measuring 0.037mg/mL. Investigation of the extract's inhibitory mechanism reveals that it acts as a non-specific inhibitor of ACE2 by exhibiting a steady-state binding affinity (KD) of 7.9×10-7M. Seventy-three percent of the high-content compounds were found to be inactive. Active compounds were identified as a group of low-content compounds, represented by Ellagic acid, working in combination. Conclusions The water extract of Bergenia purpurascens is a good and cheap non-specific ACE2 inhibitor.