A novel inhibitor of human La protein with anti-HBV activity discovered by structure-based virtual screening and in vitro evaluation.

PloS One
Jing TangJian Zhang

Abstract

Over 350 million people worldwide are infected with hepatitis B virus (HBV), a major cause of liver failure and hepatocellular carcinoma. Current therapeutic agents are highly effective, but are also associated with development of viral resistance. Therefore, strategies for identifying other anti-HBV agents with specific, but distinctive mechanisms of action are needed. The human La (hLa) protein, which forms a stabilizing complex with HBV RNA ribonucleoprotein to promote HBV replication, is a promising target of molecular therapy. This study aimed to discover novel inhibitors of hLa that could inhibit HBV replication and expression. A multistage molecular docking approach was used to screen a Specs database and an in-house library against hLa binding sites. Sequential in vitro evaluations were performed to detect potential compounds with high scores in HepG2.2.15 cells. Of the 26 potential compounds with high scores chosen for experimental verification, 12 had HBV DNA inhibition ratios of less than 50% with P<0.05. Six had significant inhibition of HBV e antigen (HBeAg) levels, and 13 had significant inhibition of HBV surface antigen (HBsAg) levels by in vitro assays. Compounds HBSC-11, HBSC-15 and HBSC-34 (HBSC is system pref...Continue Reading

References

Feb 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·M A SellsG Acs
Jan 1, 1985·Hematological Oncology·S H LevittG Frizzera
Dec 11, 1997·The New England Journal of Medicine·W M Lee
Jul 18, 2002·The Journal of Biological Chemistry·Sven HorkeTilman Heise
Mar 19, 2004·Journal of Medicinal Chemistry·Richard A FriesnerPeter S Shenkin
Jul 9, 2004·World Journal of Gastroenterology : WJG·Qin NiLing-Ling Wu
Aug 11, 2004·The Journal of Biological Chemistry·Imke EhlersTilman Heise
Aug 10, 2007·BMC Biochemistry·Stephen M T HokeChristopher J Brandl
Mar 12, 2009·Infectious Disorders Drug Targets·Lance L Stein, Rohit Loomba
May 8, 2009·Journal of Medicinal Chemistry·Chien-Shu ChenJi-Wang Chern
Jun 25, 2010·RNA·Katrin SchäfflerUtz Fischer
Jul 16, 2010·Bioorganic & Medicinal Chemistry·Tanaji T TaleleNeerja Kaushik-Basu
Nov 17, 2010·Journal of Experimental & Clinical Cancer Research : CR·Zhong-Jun WuZhi-Qiang Wang
May 3, 2011·Bioorganic & Medicinal Chemistry Letters·Nam Doo KimSoon Kil Ahn

❮ Previous
Next ❯

Citations

Nov 10, 2013·Future Microbiology·Armando AriasIan Goodfellow
Nov 2, 2012·Cancer Metastasis Reviews·Mausumi BharadwajShowket Hussain
Sep 22, 2015·Viruses·Lei KangJing Tang
Nov 21, 2012·Fitoterapia·Li-Peng Qiu, Ke-Ping Chen
Apr 10, 2015·Journal of Virology·Surender VashistIan Goodfellow
Jul 21, 2020·RNA Biology·Gunhild Sommer, Tilman Heise
Oct 27, 2016·Current Opinion in Infectious Diseases·Jiaqian PanJing Tang
Sep 23, 2020·International Journal of Molecular Sciences·Jonas WeißeTony Gutschner

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
flow cytometry
ELISA
in
transfection
PCR
electrophoresis

Software Mentioned

Glide
Maestro
GLIDE )
PyMol
LigPrep
DOCK

Related Concepts

Related Feeds

Antivirals

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

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Antivirals (ASM)

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