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

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.

Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure–Activity Relationships

“…Inhibition of HIV-1, Cat L, and Renin PRs by SB Extracts SB extract was prepared from the whole plant according to a previously described method [20]. Using a high-throughput screening approach [20,21], the safety of four SB extracts (SBW, SB30, SB60, and SB85: prepared from water or MeOH-H 2 O) was initially evaluated using renin protease (Table 1) (Please refer to the Supplementary Materials for details). SBW and SB30 had anti-human renin PR activities with IC 50 values of 0.59 and 0.70 mg/mL, respectively, suggesting that these two extracts may present minor toxicity to humans.…”

“…Molecular docking was performed for the top four inhibitors (Scutellarein, Hispidulin, Apigenin, and Luteolin) against both HIV-1 PR and Cat L PR [21]. As shown in Table 4, the binding energies of Scutellarein, Hispidulin, Apigenin, and Luteolin were −46.959 to −38.811 kcal/mol towards Cat L PR, and −56.377 to −51.378 kcal/mol towards HIV-1 PR.…”

“…The contents of luteolin and apigenin were less than 0.3 µg/mg in the SB extracts. The anti-Cat L and anti-HIV-1 PR activities of the nine flavonoids isolated from SB were screened using SensoLyte ® 520 Cathepsin L and HIV-1 Assay Kits *Fluorimetric*, respectively, according to a previously reported procedure [20,21]. The nine flavonoid compounds were scutellarin, baicalin, scutellarein, hispidulin, apigenin, luteolin, narigenin, eriodictyol, and wogonin.…”

A comprehensive review on the chemical constituents, sesquiterpenoid biosynthesis and biological activities of Sarcandra glabra

“…Jin et al [ 80 ] reported that isofraxidin ( 230 ) effectively inhibited platelet aggregation through the PI3K/AKT and mitogen‑activated protein kinase (MAPK) pathways, thereby alleviating lung inflammation induced by influenza A. In the work by Pan et al [ 158 ], SGE was found to inhibit HIV-1 protease and cathepsin L with IC 50 values ranging from 0.003 to 0.07 mg/mL and 0.11 to 0.26 mg/mL, respectively. Notably, chlorogenic acid ( 377 ), a prominent constituent of the extract, displayed the most potent inhibitory activity against the two viral proteases.…”