Dual Inhibition of HIV-1 and Cathepsin L Proteases by Sarcandra glabra

The COVID-19 pandemic continues to impose a huge threat on human health due to rapid viral mutations. Thus, it is imperative to develop more potent antivirals with both prophylactic and treatment functions. In this study, we screened for potential antiviral compounds from Sarcandra glabra (SG) against Cathepsin L and HIV-1 proteases. A FRET assay was applied to investigate the inhibitory effects and UPLC-HRMS was employed to identify and quantify the bioactive components. Furthermore, molecular docking was carried out to get a glimpse of the binding of active compounds to the proteases. Our results showed that the SG extracts (SGW, SG30, SG60, and SG85) inhibited HIV-1 protease with an IC50 of 0.003 similar to 0.07 mg/mL and Cathepsin L protease with an IC50 of 0.11 similar to 0.26 mg/mL. Fourteen compounds were identified along with eight quantified from the SG extracts. Chlorogenic acid, which presented in high content in the extracts (12.7 similar to 15.76 mu g/mg), possessed the most potent inhibitory activity against HIV-1 protease (IC50 = 0.026 mg/mL) and Cathepsin L protease (inhibition: 40.8% at 0.01 mg/mL). Thus, SG extracts and the active ingredients could potentially be used to prevent/treat viral infections, including SARS-CoV-2, due to their dual-inhibition functions against viral proteases.

Automated summary

This study screened potential antiviral compounds from Sarcandra glabra and investigated their inhibitory effects on HIV-1 and Cathepsin L proteases. The results showed that the extracts from Sarcandra glabra inhibited both proteases, with chlorogenic acid identified as the most potent inhibitor. These findings suggest that Sarcandra glabra extracts and its active ingredients may have dual-inhibition functions against viral proteases and could be used for preventing or treating viral infections, including SARS-CoV-2.