Simvastatin potentiates the anti-hepatitis B virus activity of FDA-approved nucleoside analogue inhibitors in vitro

Abstract

Statins are 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors used for the treatment of hypercholesterolemia. We report that a particular statin, simvastatin (SIM), exhibits strong in vitro anti-HBV activity. Moreover, a combination of SIM with each of the individual nucleos(t)ide analogues lamivudine (LMV), adefovir (ADV), tenofovir (TEN) and entecavir (ETV), showed synergistic antiviral activity. Combination drug treatments were performed in the HepG2.2.15 cell line. Compound combinations were centered on a mixture designed to deliver approximately equipotent (not necessarily equimolar) concentrations of each agent, based on the ninety percent viral inhibition monotherapy values. SIM interacted favorably with all four licensed anti-HBV nucleos(t)ide analogues, especially at molar ratios that approximate combinations likely to be used clinically. As the relative concentration of SIM was raised to an excess, the overall favorability of the interactions progressively increased.SIM displayed about equal degrees of synergy with ADV and TDF. The highest degree of synergy was observed at the 300:1 combination of SIM with ETV. Interactions with LMV were the least favorable. The in vitro potential shown here may greatly augment anti-HBV therapy clinically.

Development of a Novel Site-Specific Pegylated Interferon Beta for Antiviral Therapy of Chronic Hepatitis B Virus

“…As shown in Fig. 4A, the potency of the antiviral effect of 10 nM entecavir (ETV) is similar to that of 1 M TDF, which appears to be in line with previous reports indicating 50% effective concentrations (EC 50 s) of 8 to 9 nM for ETV and 0.25 to 2.4 M for TDF (22)(23)(24). Therefore, we analyzed the synergistic anti-HBV effect of PEG-IFN used concomitantly with 10 nM ETV or 1 M TDF.…”

Antiviral drug discovery: broad-spectrum drugs from nature

“…The addition of geranylgeraniol, which is involved in protein trafficking to membrane compartments, restored viral replication thus suggesting a non-direct antiviral activity of statins. Antiviral effects of statins have also been described for HBV, HIV, influenza virus, DENV, HCMV and norovirus [161][162][163][164][165][166][167][168][169] . However the antiviral efficacy of statins in vivo was only marginal and drug-drug interactions with DAAs have been reported 170,171 .…”

The supercritical CO2 extract from the skin of Bufo bufo gargarizans Cantor blocks hepatitis B virus antigen secretion in HepG2.2.15 cells

“…Hepatitis B virus (HBV), a member of the hepadnavirus (hepatotropic DNA viruses) family, infects approximate 400 million people, making it the most common chronic infectious disease worldwide (1). Chronic HBV infection can lead to cirrhosis, liver failure, and hepatocellular carcinoma, accounting for more than a million global deaths annually (2,3).…”