Rosmarinic acid is a novel inhibitor for Hepatitis B virus replication targeting viral epsilon RNA-polymerase interaction

PloS One
Yuta TsukamotoTakashi Fujita

Abstract

Current therapeutics for hepatitis B virus (HBV) patients such as nucleoside analogs (NAs) are effective; however, new antiviral drugs against HBV are still desired. Since the interaction between the epsilon (ε) sequence of HBV pregenomic RNA and viral polymerase (Pol) is a key step in the HBV replication cycle, we aimed to identify small compounds for its inhibition, and established a pull-down assay system for the detection of ε-RNA-binding-Pol. Screening showed that 5 out of 3,965 compounds inhibited ε-Pol binding, and we identified rosmarinic acid, which exhibited specificity, as a potential antiviral agent. In order to examine the anti-HBV effects of rosmarinic acid, HBV-infected primary human hepatocytes from a humanized mouse liver were treated with rosmarinic acid. The rosmarinic acid treatment decreased HBV components including the amounts of extracellular HBV DNA with negligible cytotoxicity. We also investigated the combined effects of rosmarinic acid and the NA, lamivudine. rosmarinic acid slightly enhanced the anti-HBV activity of lamivudine, suggesting that the HBV replication step targeted by rosmarinic acid is distinct from that of NA. We analyzed an additional 25 rosmarinic acid derivatives, and found that 5 al...Continue Reading

References

Sep 29, 2006·Journal of Molecular Recognition : JMR·Stephen J Stray, Adam Zlotnick
Sep 10, 2009·Gastroenterology·Fabien Zoulim, Stephen Locarnini
Feb 18, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Thomas J CradickAnton P McCaffrey
Sep 3, 2011·Immunological Reviews·Hiroki KatoTakashi Fujita
Jul 26, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kristie BloomPatrick Arbuthnot
Sep 13, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jieliang ChenZhenghong Yuan
Aug 20, 2014·Molecular Therapy. Nucleic Acids·Su-Ru LinPei-Jer Chen
Aug 26, 2014·Biochemical and Biophysical Research Communications·Naoki OguraTakaji Wakita
Dec 3, 2014·Antimicrobial Agents and Chemotherapy·Gaofeng LuJohn E Tavis
Dec 17, 2014·Molecular Therapy. Nucleic Acids·Christoph Seeger, Ji A Sohn
Jun 4, 2015·Scientific Reports·Vyas RamananSangeeta N Bhatia
Nov 12, 2017·Antiviral Research·Katrin SchöneweisAndrew Vaillant

❮ Previous
Next ❯

Citations

May 18, 2020·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Xiao-Quan LiuKeiji Ueda
Jan 10, 2019·Journal of Biomedical Science·Jonatas Rafael de OliveiraLuciane Dias de Oliveira
Dec 31, 2020·BioMed Research International·Xuqiang LiuWenyi Kang
Mar 4, 2021·Journal of Agricultural and Food Chemistry·Fazlurrahman KhanYoung-Mog Kim
May 4, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Minglong GuanXiaoyun Fan
Aug 28, 2021·Nutrients·Amélia DelgadoAnthony Fardet

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
PCR
reverse transcription PCR
pull-down
electrophoresis
transfection
helicase assay

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.