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. 2022 Aug 29;27(17):5552.
doi: 10.3390/molecules27175552.

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

Bowen Pan  1 , Sumei Li  2 , Junwei Xiao  1 , Xin Yang  1 , Shouxia Xie  2 , Ying Zhou  1 , Jian Yang  3 , Ying Wei  1
Affiliations

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

Bowen Pan et al. Molecules. .

Abstract

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 0.003~0.07 mg/mL and Cathepsin L protease with an IC50 of 0.11~0.26 mg/mL. Fourteen compounds were identified along with eight quantified from the SG extracts. Chlorogenic acid, which presented in high content in the extracts (12.7~15.76 µg/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.

Keywords: Cathepsin L protease; HIV-1 protease; Sarcandra glabra; UPLC-HRMS; inhibition; molecular docking.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The chemical profile of SG extracts analyzed by UPLC-MS (positive). The numbers indicate the compounds.
Figure 2
Figure 2
The chemical profile of SG extracts analyzed by UPLC-MS (negative). The numbers indicate the compounds.
Figure 3
Figure 3
Predicted binding of chlorogenic acid (a) and rosmarinic acid (b) to CatL PR.
Figure 4
Figure 4
Predicted binding of 3,4-dicaffeoylquinic acid (a), rosmarinic acid (b), and chlorogenic acid (c) to HIV-1 PR.
See this image and copyright information in PMC

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