Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA. Electronic address:
Published: September 2015
AI Article Synopsis
Article Abstract
The design and synthesis of new non-symmetrical NS5A inhibitors with sulfur containing amino acids is reported along with their ability to block HCV replication in an HCV 1b replicon system. These compounds display EC50 values in the picomolar range with a large therapeutic index (>10(6)). Moreover, cellular pharmacology studies show that our preferred compounds intracellularly deliver three potent NS5A inhibitors.
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.
According to World Health Organization reports of the year 2022, nearly 242,000 people died from hepatitis C that causes liver cirrhosis and hepatocellular carcinoma. Phosphatidylinositol-4-kinase type III alpha (PI4KIIIα), a lipid kinase interacts with the hepatitis C virus non-structural 5 A protein (NS5A) to produce phosphoinositol-4-phosphate (PI4P), which enriches the hepatitis C virus replication complex. Patients with hepatitis C virus infection in the liver have been associated with increased levels of PI4P at the endoplasmic reticulum.
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.
Hepatitis C virus (HCV) is a pathogen that causes cirrhosis and hepatocellular carcinoma through chronic hepatitis C. This study focused on the anti-HCV activity of a 70% ethanol extract of Nakai (KKE) and its bioactive chemical constituent(s). The KKE and its -butanol (-BuOH) fraction induced a significant reduction in HCV RNA levels without inducing cytotoxicity.
Direct oral anticoagulants (DOACs) are recommended for the management of thrombosis prophylaxis, especially in patients with atrial fibrillation. As substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, they are implicated in potential drug-drug interactions. NS5A/NS5B inhibitors are direct-acting agents (DAAs) against the Hepatitis C Virus (HCV) infection that exert a mild inhibition of P-glycoprotein without effects on CYP3A4.
