5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. The synthesis, structure-activity relationships (SAR), metabolic stability, and structure-based design approach for this new class of compounds are discussed.
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http://dx.doi.org/10.1016/j.bmcl.2008.01.007 | DOI Listing |
J Med Chem
January 2025
Department of Ophthalmology, Tianjin Medical University General Hospital, International Joint Laboratory of Ocular Diseases (Ministry of Education), Tianjin Key Laboratory of Ocular Trauma, Tianjin Institute of Eye Health and Eye Diseases, China-U.K. "Belt and Road" Ophthalmology Joint Laboratory, Laboratory of Molecular Ophthalmology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Although interferon-free direct-acting antivirals have led to significant advancements in the treatment of HCV infection, the high genetic variability of the virus and the emergence of acquired drug resistance pose potential threats to their effectiveness. In this study, we develop a broad-spectrum aptamer-based proteolysis targeting chimera, designated dNS5B, which effectively degrades both pan-genotypic NS5B polymerase and drug-resistant mutants through ubiquitin proteasome system.
View Article and Find Full Text PDFPharmaceuticals (Basel)
December 2024
COSYS/IMSE, Université Gustave Eiffel, Champs-sur-Marne, 77454 Marne-la-Vallée, Cedex 2, France.
RNA polymerase (NS5B), serves as a crucial target for pharmaceutical interventions aimed at combating the hepatitis C virus (HCV), which poses significant health challenges worldwide. The present research endeavors to explore and implement a variety of advanced molecular modeling techniques that aim to create and identify innovative and highly effective inhibitors that specifically target the RNA polymerase enzyme. In this study, a QSAR investigation was carried out on a set of thirty-eight isothiazole derivatives targeting NS5B inhibition and thus hepatitis C virus (HCV) treatment.
View Article and Find Full Text PDFClin Infect Dis
December 2024
Department of Medicine, Denver Health Medical Center, Denver, Colorado, USA.
Background: Simplified approaches to HCV treatment delivery are needed to meet elimination goals. However, the impact of low-touch strategies on individuals at higher risk due to treatment failure or reinfection is unknown. We estimated HCV reinfection rates, and the impact of resistance associated substitutions (RASs) on response in the ACTG A5360 (MINMON) trial.
View Article and Find Full Text PDFJ Virol Methods
December 2024
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address:
Background: Hepatitis C virus (HCV) resistance-associated substitutions (RASs) have a significant impact on the treatment of HCV with direct-acting antivirals (DAAs). However, limited research has been conducted, and no standardized methods for detecting RASs in mainland China.
Objectives: To develop and apply a novel method for detecting HCV RASs in HCV RNA-positive patients in Linzhou, China.
Biomed Eng Comput Biol
December 2024
PharmaQsar Bioinformatics Firm, Kampala, Uganda.
Introduction: The rate of acute hepatitis C increased by 7% between 2020 and 2021, after the number of cases doubled between 2014 and 2020. With the current adoption of pan-genotypic HCV therapy, there is a need for improved availability and accessibility of this therapy. However, double and triple DAA-resistant variants have been identified in genotypes 1 and 5 with resistance-associated amino acid substitutions (RAASs) in NS3/4A, NS5A, and NS5B.
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