BIOMAT Database Logo BIOMAT Database Logo

MEAN inhibits hepatitis C virus replication by interfering with a polypyrimidine tract-binding protein. 2016

Jihua Xue, and Yanning Liu, and Ying Yang, and Shanshan Wu, and Ying Hu, and Fan Yang, and Xiaotang Zhou, and Jing Wang, and Feng Chen, and Min Zheng, and Haihong Zhu, and Zhi Chen
State Key Lab of Diagnostic and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, 1st Affiliated Hospital of Medical School, Zhejiang University, Hangzhou, China.

MEAN (6-methoxyethylamino-numonafide) is a small molecule compound, and here, we report that it effectively inhibits hepatitis C virus (HCV) infection in an HCV cell culture system using a JC1-Luc chimeric virus, with a 50% effective concentration (EC50) of 2.36 ± 0.29 μM. Drug combination usage analyses demonstrated that MEAN was synergistic with interferon α, ITX5061 and ribavirin. In addition, MEAN effectively inhibits N415D mutant virus and G451R mutant viral infections. Mechanistic studies show that the treatment of HCV-infected hepatocytes with MEAN inhibits HCV replication but not translation. Furthermore, treatment with MEAN significantly reduces polypyrimidine tract-binding protein (PTB) levels and blocks the cytoplasmic redistribution of PTB upon infection. In the host cytoplasm, PTB is directly associated with HCV replication, and the inhibition of HCV replication by MEAN can result in the sequestration of PTB in treated nuclei. Taken together, these results indicate that MEAN is a potential therapeutic candidate for HCV infection, and the targeting of the nucleo-cytoplasmic translocation of the host PTB protein could be a novel strategy to interrupt HCV replication.

UI MeSH Term Description Entries
D010655 Phenylenediamines Aniline compounds that contain two amino groups. They are used as a precursor in the synthesis of HETEROCYCLIC COMPOUNDS and POLYMERS. p-Phenylenediamine is used in the manufacture of HAIR DYES and is an ALLERGEN.
D003593 Cytoplasm The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990) Protoplasm,Cytoplasms,Protoplasms
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D006526 Hepatitis C INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown. Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted,Parenterally-Transmitted Non-A, Non-B Hepatitis,PT-NANBH,Parenterally Transmitted Non A, Non B Hepatitis
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000067556 Internal Ribosome Entry Sites Sequences within MESSENGER RNA that enable PROTEIN TRANSLATION INITIATION independent of 5' CAPPED RNA. Internal Ribosome Entry Site
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D012254 Ribavirin A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. Ribovirin,Tribavirin,ICN-1229,Rebetol,Ribamide,Ribamidil,Ribamidyl,Ribasphere,Vilona,Viramide,Virazide,Virazole,ICN 1229,ICN1229
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012367 RNA, Viral Ribonucleic acid that makes up the genetic material of viruses. Viral RNA

Related Publications

Jihua Xue, and Yanning Liu, and Ying Yang, and Shanshan Wu, and Ying Hu, and Fan Yang, and Xiaotang Zhou, and Jing Wang, and Feng Chen, and Min Zheng, and Haihong Zhu, and Zhi Chen
Viperin inhibits hepatitis C virus replication by interfering with binding of NS5A to host protein hVAP-33.
January 2012, The Journal of general virology,
Jihua Xue, and Yanning Liu, and Ying Yang, and Shanshan Wu, and Ying Hu, and Fan Yang, and Xiaotang Zhou, and Jing Wang, and Feng Chen, and Min Zheng, and Haihong Zhu, and Zhi Chen
Role of Ras-related Nuclear Protein/Polypyrimidine Tract Binding Protein in Facilitating the Replication of Hepatitis C Virus.
August 2021, Journal of clinical and translational hepatology,
Jihua Xue, and Yanning Liu, and Ying Yang, and Shanshan Wu, and Ying Hu, and Fan Yang, and Xiaotang Zhou, and Jing Wang, and Feng Chen, and Min Zheng, and Haihong Zhu, and Zhi Chen
The polypyrimidine tract-binding protein (PTB) is required for efficient replication of hepatitis C virus (HCV) RNA.
January 2006, Virus research,
Jihua Xue, and Yanning Liu, and Ying Yang, and Shanshan Wu, and Ying Hu, and Fan Yang, and Xiaotang Zhou, and Jing Wang, and Feng Chen, and Min Zheng, and Haihong Zhu, and Zhi Chen
Polypyrimidine tract-binding protein (PTB) inhibits Hepatitis C virus internal ribosome entry site (HCV IRES)-mediated translation, but does not affect HCV replication.
October 2004, Archives of virology,
Jihua Xue, and Yanning Liu, and Ying Yang, and Shanshan Wu, and Ying Hu, and Fan Yang, and Xiaotang Zhou, and Jing Wang, and Feng Chen, and Min Zheng, and Haihong Zhu, and Zhi Chen
HuR Displaces Polypyrimidine Tract Binding Protein To Facilitate La Binding to the 3' Untranslated Region and Enhances Hepatitis C Virus Replication.
November 2015, Journal of virology,
Jihua Xue, and Yanning Liu, and Ying Yang, and Shanshan Wu, and Ying Hu, and Fan Yang, and Xiaotang Zhou, and Jing Wang, and Feng Chen, and Min Zheng, and Haihong Zhu, and Zhi Chen
Interfering with hepatitis C virus RNA replication.
June 2004, Virus research,
Jihua Xue, and Yanning Liu, and Ying Yang, and Shanshan Wu, and Ying Hu, and Fan Yang, and Xiaotang Zhou, and Jing Wang, and Feng Chen, and Min Zheng, and Haihong Zhu, and Zhi Chen
Polypyrimidine-Tract-Binding Protein Isoforms Differentially Regulate the Hepatitis C Virus Internal Ribosome Entry Site.
December 2022, Viruses,
Jihua Xue, and Yanning Liu, and Ying Yang, and Shanshan Wu, and Ying Hu, and Fan Yang, and Xiaotang Zhou, and Jing Wang, and Feng Chen, and Min Zheng, and Haihong Zhu, and Zhi Chen
Cytoplasmic translocation of polypyrimidine tract-binding protein and its binding to viral RNA during Japanese encephalitis virus infection inhibits virus replication.
January 2014, PloS one,
Jihua Xue, and Yanning Liu, and Ying Yang, and Shanshan Wu, and Ying Hu, and Fan Yang, and Xiaotang Zhou, and Jing Wang, and Feng Chen, and Min Zheng, and Haihong Zhu, and Zhi Chen
Hepatitis A virus (HAV) proteinase 3C inhibits HAV IRES-dependent translation and cleaves the polypyrimidine tract-binding protein.
September 2010, Journal of viral hepatitis,
Jihua Xue, and Yanning Liu, and Ying Yang, and Shanshan Wu, and Ying Hu, and Fan Yang, and Xiaotang Zhou, and Jing Wang, and Feng Chen, and Min Zheng, and Haihong Zhu, and Zhi Chen
Bortezomib inhibits chikungunya virus replication by interfering with viral protein synthesis.
May 2020, PLoS neglected tropical diseases,
Copied contents to your clipboard!