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

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Antiviral Research

Volume 86, Issue 3, June 2010, Pages 241-245

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doi:10.1016/j.antiviral.2010.02.325 | How to Cite or Link Using DOI

Published by Elsevier B.V.

Simvastatin potentiates the anti-hepatitis B virus activity of FDA-approved

nucleoside analogue inhibitors in vitro

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Ted Badera, , and Brent Korbab,

a Section of Gastroenterology, Department of Medicine, University of Oklahoma

Health Sciences Center, VA Medical Center, Mailstop 111H, 921 NE 13th Street,

Oklahoma City, OK 73104, USA

b Department of Microbiology, town University Medical Center, 3900

Reservoir Road, NW, Med-Dent. Building, Room SW319, Washington, DC 20057, USA

Received 25 November 2009; revised 28 January 2010; accepted 26 February 2010.

Available online 6 March 2010.

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.

Corresponding author at: VA Medical Center, Mailstop 111H, 921 NE 13th Street,

Oklahoma City, OK 73104, USA. Tel.: +1 405 456 5313; fax: +1 405 456 5946.

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