Inhibitory Effects of Amentoflavone and Orobol on Daclatasvir-Induced Resistance-Associated Variants of Hepatitis C Virus

2018 ◽  
Vol 46 (04) ◽  
pp. 835-852 ◽  
Author(s):  
Wei-Ping Lee ◽  
Keng-Li Lan ◽  
Shi-Xian Liao ◽  
Yi-Hsiang Huang ◽  
Ming-Chih Hou ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Entry ◽  
Antiviral Agents ◽  
Cost Effective ◽  
Pegylated Interferon ◽  
Chinese Herbs ◽  
Inhibitory Effects ◽  
Direct Acting Antiviral ◽  
Direct Acting

Hepatitis C virus (HCV) is recognized as a major causative agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Despite rapid progress in the development of direct-acting antivirals (DAA) against HCV infection in recent years, cost-effective antiviral drugs with more affordable prices still need to be developed. In this study, we screened a library of natural compounds to identify natural HCV inhibitors. The library of the pure compounds extracted from Chinese herbs deposited in the chemical bank of National Research Institute of Chinese Medicine (NRICM), Taiwan was screened in the cell culture-derived HCV (HCVcc) system. We identified the flavone or flavan-based compounds amentoflavone, 7,4[Formula: see text]-dihydroxyflavanone, and orobol with the inhibition of viral entry, replication, and translation of the HCV life cycle. Amentoflavone and orobol also showed inhibitory effects on resistant-associated variants to the NS5A inhibitor daclatasvir. The results of this study have the potential to benefit patients who are intolerant to the adverse effect of pegylated interferon or who harbor resistant strains refractory to treatment by current direct-acting antiviral agents.

scholarly journals Different Interaction Profiles of Direct-Acting Anti-Hepatitis C Virus Agents with Human Organic Anion Transporting Polypeptides

2014 ◽  
Vol 58 (8) ◽  
pp. 4555-4564 ◽  
Author(s):  
Tomomi Furihata ◽  
Shogo Matsumoto ◽  
Zhongguo Fu ◽  
Akihito Tsubota ◽  
Yuchen Sun ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Organic Anion ◽  
Antiviral Agents ◽  
Inhibitory Effects ◽  
Essential Information ◽  
Direct Acting Antiviral ◽  
Hcv Therapy ◽  
Direct Acting ◽  
Inhibition Potency

ABSTRACTSimeprevir (SMV), asunaprevir (ASV), daclatasvir (DCV), and sofosbuvir (SFV), which are newly developed direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection, are among the key components of anti-HCV regimens. Preclinical studies have identified inhibitory properties for some of these DAAs against organic anion transporting polypeptide 1B (OATP1B) functions. However, their details remain mostly uncharacterized. Because OATP1B1 and OATP1B3 play determinant roles in the pharmacokinetics of various drugs via their uptake into human hepatocytes, it is plausible that the inhibition of these OATP1Bs by a DAA would create a potential risk of drug-drug interaction, which has been an emerging concern in anti-HCV therapy. Accordingly, in the present study, we intended to clarify the inhibitory characteristics of newly developed DAAs toward OATP1B1 and -1B3 functions. The results of our coincubation inhibition assays have shown that all tested DAAs could inhibit OATP1B1 functions and that SMV, ASV, and DCV (to a lesser extent), but not SFV, exhibited long-lasting preincubation inhibitory effects on OATP1B1 functions. It was also found that the preincubation inhibitory effects of SMV and ASV could augment their coincubation inhibition potency. Furthermore, significant, but differential, inhibitory effects of the DAAs on the OATP1B3 function were identified. To summarize, our results clearly show that the newly developed DAAs are newly identified OATP1B1 and OATP1B3 inhibitors with distinctive interaction properties. It is believed that these inhibition profiles will provide essential information to all concerned parties with respect to the clinical significance of DAA-mediated inhibition of OATP1Bs in anti-HCV therapy.

Viral Hepatitis C: Treatment

2018 ◽  
Author(s):  
Jay Luther ◽  
Raymond T. Chung ◽  
Anna Lidofsky ◽  
Jacinta A Holmes ◽  
Stephanie M Rutledge
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Pegylated Interferon ◽  
Direct Acting Antiviral ◽  
Hcv Therapy ◽  
Viral Hepatitis C ◽  
Pegylated Interferon Plus Ribavirin ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Infection with the hepatitis C virus (HCV) leads to chronic infection in the majority, and is associated with the development of complications including cirrhosis, end-stage liver failure, hepatocellular carcinoma and death. HCV is curable, and successful viral eradication is associated with a reduction in cirrhosis and liver-related mortality. However, previous HCV therapy, consisting of pegylated interferon plus ribavirin, was associated with poor cure rates and significant adverse events. The development of direct-acting antiviral agents (DAAs) that specifically target HCV replication has revolutionized the treatment of HCV. Current regimens are now highly potent, all-oral, interferon-free combinations of these DAAs. The Food and Drug Administration has now approved many of these regimens. The changing management of HCV infection, including recent advances in HCV therapy, are discussed. This review contains 1 figure, 5 tables and 59 references Key words: direct-acting antiviral agents, hepatitis C virus, interferon-free therapy, management, treatment

New direct-acting antiviral agents for the treatment of hepatitis C virus infection and perspectives

Gut ◽  
2012 ◽  
Vol 61 (Suppl 1) ◽  
pp. i36-i46 ◽  
Author(s):  
Christoph Welsch ◽  
Arun Jesudian ◽  
Stefan Zeuzem ◽  
Ira Jacobson
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Pegylated Interferon ◽  
The Novel ◽  
Genotype 1 ◽  
Direct Acting Antiviral ◽  
Hcv Therapy ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Until recently, the standard of care (SOC) for patients with chronic hepatitis C virus (HCV) infection has consisted of a combination of pegylated interferon-N1 plus ribavirin, administered for 24- to 48-weeks depending on the HCV genotype. The sustained virologic response rate for this SOC has been only about 50% in patients infected with genotype 1 HCV, the most prevalent genotype in Europe and North America. HCV therapy has been revolutionised recently by the approval of two direct-acting antiviral agents (DAA) against the NS3/4A serine protease for use in genotype 1 HCV, the ketoamide inhibitors boceprevir and telaprevir. The novel SOC marks the beginning of an extraordinary new era in HCV therapy. We review this new SOC with an emphasis on practical issues related to protease inhibitors, e.g. prescribing guidelines, futility rules and management of adverse events. We also give a perspective on what to expect in the coming years. Newer DAA with simplified dosing regimens and/or minimal toxicity which, when used in combination, will lead to viral eradication in most if not all CHC patients who undergo treatment. The novel agents in clinical development are paving the way for future interferon-sparing regimens.

Viral Hepatitis C: Treatment

2018 ◽  
Author(s):  
Jay Luther ◽  
Raymond T. Chung ◽  
Anna Lidofsky ◽  
Jacinta A Holmes ◽  
Stephanie M Rutledge
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Pegylated Interferon ◽  
Direct Acting Antiviral ◽  
Hcv Therapy ◽  
Viral Hepatitis C ◽  
Pegylated Interferon Plus Ribavirin ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Infection with the hepatitis C virus (HCV) leads to chronic infection in the majority, and is associated with the development of complications including cirrhosis, end-stage liver failure, hepatocellular carcinoma and death. HCV is curable, and successful viral eradication is associated with a reduction in cirrhosis and liver-related mortality. However, previous HCV therapy, consisting of pegylated interferon plus ribavirin, was associated with poor cure rates and significant adverse events. The development of direct-acting antiviral agents (DAAs) that specifically target HCV replication has revolutionized the treatment of HCV. Current regimens are now highly potent, all-oral, interferon-free combinations of these DAAs. The Food and Drug Administration has now approved many of these regimens. The changing management of HCV infection, including recent advances in HCV therapy, are discussed. This review contains 1 figure, 5 tables and 59 references Key words: direct-acting antiviral agents, hepatitis C virus, interferon-free therapy, management, treatment

Viral Hepatitis C: Treatment

2018 ◽  
Author(s):  
Jay Luther ◽  
Raymond T. Chung ◽  
Anna Lidofsky ◽  
Jacinta A Holmes ◽  
Stephanie M Rutledge
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Pegylated Interferon ◽  
Direct Acting Antiviral ◽  
Hcv Therapy ◽  
Viral Hepatitis C ◽  
Pegylated Interferon Plus Ribavirin ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Infection with the hepatitis C virus (HCV) leads to chronic infection in the majority, and is associated with the development of complications including cirrhosis, end-stage liver failure, hepatocellular carcinoma and death. HCV is curable, and successful viral eradication is associated with a reduction in cirrhosis and liver-related mortality. However, previous HCV therapy, consisting of pegylated interferon plus ribavirin, was associated with poor cure rates and significant adverse events. The development of direct-acting antiviral agents (DAAs) that specifically target HCV replication has revolutionized the treatment of HCV. Current regimens are now highly potent, all-oral, interferon-free combinations of these DAAs. The Food and Drug Administration has now approved many of these regimens. The changing management of HCV infection, including recent advances in HCV therapy, are discussed. This review contains 1 figure, 5 tables and 59 references Key words: direct-acting antiviral agents, hepatitis C virus, interferon-free therapy, management, treatment

Effect on the adherence to concomitant medications after initiation of treatment with direct-acting antiviral agents against hepatitis C virus

2020 ◽  
Vol 43 (8) ◽  
pp. 418-425
Author(s):  
Maria Isabel Guzman Ramos ◽  
Mercedes Manzano-García ◽  
M. de las Aguas Robustillo-Cortés ◽  
Juan Antonio Pineda ◽  
Ramón Morillo-Verdugo
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Direct Acting Antiviral ◽  
Concomitant Medications ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents
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