Asunaprevir (ASV), an isoquinoline-based competitive inhibitor targeting the hepatitis C virus (HCV) NS3/4A protease, is very potent in vivo. However, the potency is significantly compromised by the drug resistance mutations R155K and D168A. In this study three crystal structures of ASV and an analogue were determined to analyze the structural basis of drug resistance susceptibility. These stru...

Background: Hepatitis C virus (HCV) infection a major disorder that is not only a liver-related disease but also a cardiovascular complication in renal transplant recipient. Interferon-based therapy is a contraindication after transplantation because interferon is possibly induced to graft rejection. Only limited anecdotal evidence exists on the antiviral efficacy and tolerability of HCV direct...

Direct-acting antiviral (DAA) drugs exhibit considerable variability in mechanisms of metabolism and the extent to which they are substrates, inhibitors, or inducers of cytochrome P450 enzymes or P-glycoprotein and other drug transporters. Thus, potential drug-drug interactions with other commonly used therapies also vary, as do the effects of renal and hepatic impairment on DAA drug exposure. ...

978-0-9798064-0-7/μTAS2007/$20©2007CBMS 251 Figure 1: ASV measurement of heavy metal using planar Bi electrode. (a) Pb and Cd start to deposit on the electrode at preconcentration potential; (b) deposited metals form multicomponent alloys with Bi; (c) Cd is first stripped from the electrode, and generates a peak current at its reduction potential, and (d) Pb is stripped off and generates anothe...

Oral direct-acting antivirals comprise the main therapy for hepatitis C virus (HCV)-associated liver disease in Japan. Daclatasvir/asunaprevir is the primary agent and sofosbuvir/ledipasvir is the secondary agent for HCV genotype 1b. Ombitasvir/paritaprevir/ritonavir was also recommended as a therapy for HCV genotype 1b. More recently, elbasvir (NS5A inhibitor)/grazoprevir (NS3/4A protease inhi...

Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokin...