AI Article Synopsis
- The hepatitis C virus (HCV) non-structural protein 3 (NS3) is crucial for viral replication, having both protease and helicase functions.
- Researchers developed an improved RNA aptamer called NEO-III-14U, which more effectively inhibits NS3 protease activity compared to a previous version, G9 aptamers.
- NEO-III-14U also successfully inhibits NS3 helicase activity and can disrupt interactions between NS3 and HCV RNA, demonstrating effectiveness in living cells.
Article Abstract
The hepatitis C virus non-structural protein 3 (HCV NS3) possesses both protease and helicase activities that are essential for viral replication. In a previous study, we obtained RNA aptamers that specifically and efficiently inhibited NS3 protease activity (G9 aptamers). In order to add helicase-inhibition capability, we attached (U)14 to the 3'-terminal end of a minimized G9 aptamer, DeltaNEO-III. NEO-III-14U was shown to inhibit the NS3 protease activity more efficiently than the original aptamer and, furthermore, to efficiently inhibit the unwinding reaction by NS3 helicase. In addition, NEO-III-14U has the potential to diminish specific interactions between NS3 and the 3'-UTR of HCV-positive and -negative strands. NEO-III-14U showed effective inhibition against NS3 protease in living cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2004.10.089 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Achievements and Approaches in the Search for Small-Molecule Dengue NS2B/NS3 Inhibitors.
Curr Med Chem
January 2025
Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.
With the escalation of viral infections in recent decades, including the COVID- 19 pandemic, viral infectious diseases have increasingly become a global concern, attracting significant attention. Among many viral epidemics, the dengue virus, an RNA virus from the Flaviviridae family, has been reported by the WHO as one of the most prevalent mosquito-borne diseases, infecting roughly 400 million people yearly and spreading across all continents worldwide. In the last two decades, researchers from academia and industry have diligently studied many aspects of the virus, including its structure, life cycle, potential therapeutic agents, and vaccines.
View Article and Find Full Text PDFIdentifying Allosteric Small-Molecule Binding Sites of Inactive NS2B-NS3 Proteases of Pathogenic .
Viruses
December 2024
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, CA 92093-0657, USA.
Dengue, West Nile, Zika, Yellow fever, and Japanese encephalitis viruses persist as significant global health threats. The development of new therapeutic strategies based on inhibiting essential viral enzymes or viral-host protein interactions is problematic due to the fast mutation rate and rapid emergence of drug resistance. This study focuses on the NS2B-NS3 protease as a promising target for antiviral drug development.
View Article and Find Full Text PDFPrevalence of resistance-associated substitutions (RAS) in hepatitis C virus in the Former Soviet Union countries.
BMJ Open Gastroenterol
January 2025
Department of Biomedical Sciences, Nazarbayev University School of Medicine, Astana, Kazakhstan
Objective: The emergence of resistance-associated substitutions (RASs) poses a significant challenge to the effective treatment of hepatitis C virus (HCV) infection using direct-acting antivirals. This study's objective was to observe the prevalence of HCV genotypes and RAS within the Former Soviet Union (FSU) countries.
Methods: We analysed 60 NS3, 313 NS5A and 1119 NS5B sequences of HCV deposited in open-access databases from 11 FSU countries for the prevalence of genotypes and the presence of RAS using the Geno2Pheno software.
Evaluation of methoxyflavones as dengue NS2B-NS3 protease inhibitors: an in silico and in vitro studies.
Mol Divers
January 2025
Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, 81310, Johor Bahru, Johor, Malaysia.
Dengue is one of the most prevalent viruses transmitted by the Aedes aegypti mosquitoes. Currently, no specific medication is available to treat dengue diseases. The NS2B-NS3 protease is vital during post-translational processing, which is a key target in this study.
View Article and Find Full Text PDFIntroduction: The purpose of our study was to evaluate the safety, tolerability, and pharmacokinetics of furaprevir, a new highly selective hepatitis C virus NS3/4A protease inhibitor.
Methods: The study was divided into 2 parts: Part A (single ascending-dose study, SAD) and Part B (multiple ascending-dose study, MAD). A total of 62 healthy subjects were enrolled in the studies.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!