Abstract
Hepatitis C virus (HCV) infection affects about 160 million people worldwide. It is treated with pegylatedinterferon (peg-IFN) and ribavirin, and in the case of patients affected by genotype 1, also with a protease inhibitor (telaprevir or boceprevir). Despite a good success rate, IFN-based combinations are contraindicated in several patients (e.g. decompensated cirrhosis, patients with psychiatric disorders, severe heart diseases or autoimmune disorders) and are associated with frequent adverse events that ultimately reduce their use. Numerous oral drugs are in an advanced phase of clinical development, and in some cases, in IFN-free combinations. This review focuses on preclinical and clinical data regarding daclatasvir (BMS-790052), which is a highly selective HCV NS5A replication complex inhibitor effective against HCV genotypes 1, 2, 3 and 4. In vitro data show that daclatasvir exerts a very potent antiviral effect against several HCV genotypes. Its pharmacokinetics is optimal and allows once-a-day oral administration. Its adverse event profile is good. Clinical data regarding its efficacy in combination with peg-IFN, ribavirin or other direct antiviral agents are impressive (rates of sustained virological response range between 60% and 100% in treatment-naïve patients). The only drawback of this drug appears to be a relatively low genetic barrier to resistance. In conclusion, daclatasvir, especially in combinations with other antiviral agents, is a very promising drug for the treatment of chronic hepatitis C.
Keywords: Combination therapy, daclatasvir, hepatitis C virus, Interferon-free, pegylated-interferon, polymerase inhibitors, resistance, ribavirin.
Current Medicinal Chemistry
Title:Daclatasvir: The First of a New Class of Drugs Targeted Against Hepatitis C Virus NS5A
Volume: 21 Issue: 12
Author(s): I. Gentile, F. Borgia, N. Coppola, A.R. Buonomo, G. Castaldo and G. Borgia
Affiliation:
Keywords: Combination therapy, daclatasvir, hepatitis C virus, Interferon-free, pegylated-interferon, polymerase inhibitors, resistance, ribavirin.
Abstract: Hepatitis C virus (HCV) infection affects about 160 million people worldwide. It is treated with pegylatedinterferon (peg-IFN) and ribavirin, and in the case of patients affected by genotype 1, also with a protease inhibitor (telaprevir or boceprevir). Despite a good success rate, IFN-based combinations are contraindicated in several patients (e.g. decompensated cirrhosis, patients with psychiatric disorders, severe heart diseases or autoimmune disorders) and are associated with frequent adverse events that ultimately reduce their use. Numerous oral drugs are in an advanced phase of clinical development, and in some cases, in IFN-free combinations. This review focuses on preclinical and clinical data regarding daclatasvir (BMS-790052), which is a highly selective HCV NS5A replication complex inhibitor effective against HCV genotypes 1, 2, 3 and 4. In vitro data show that daclatasvir exerts a very potent antiviral effect against several HCV genotypes. Its pharmacokinetics is optimal and allows once-a-day oral administration. Its adverse event profile is good. Clinical data regarding its efficacy in combination with peg-IFN, ribavirin or other direct antiviral agents are impressive (rates of sustained virological response range between 60% and 100% in treatment-naïve patients). The only drawback of this drug appears to be a relatively low genetic barrier to resistance. In conclusion, daclatasvir, especially in combinations with other antiviral agents, is a very promising drug for the treatment of chronic hepatitis C.
Export Options
About this article
Cite this article as:
Gentile I., Borgia F., Coppola N., Buonomo A.R., Castaldo G. and Borgia G., Daclatasvir: The First of a New Class of Drugs Targeted Against Hepatitis C Virus NS5A, Current Medicinal Chemistry 2014; 21 (12) . https://dx.doi.org/10.2174/0929867321666131228222215
DOI https://dx.doi.org/10.2174/0929867321666131228222215 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the Treatment of Chronic Inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Role of Calcium and the L-Type Calcium Channel in Pathological Remodeling of the Heart
Vascular Disease Prevention (Discontinued) Current Status of Rho-Associated Kinases (ROCKs) in Coronary Atherosclerosis and Vasospasm
Cardiovascular & Hematological Agents in Medicinal Chemistry Effects of Dietary Polyunsaturated Fatty Acids on Mitochondria
Current Pharmaceutical Design Therapeutic Potential of Plant Extracts and Phytochemicals Against Brain Ischemia-Reperfusion Injury: A Review
The Natural Products Journal The Versatile Stress Protein Mortalin as a Chaperone Therapeutic Agent
Protein & Peptide Letters Tanshinones: An Update in the Medicinal Chemistry in Recent 5 Years
Current Medicinal Chemistry Recent Patents on Polymeric Scaffolds for Tissue Engineering
Recent Patents on Biomedical Engineering (Discontinued) Current Problems with Non-Specific COX Inhibitors
Current Pharmaceutical Design Effects of Huangkui Capsule on the Expression of SPARC in the Kidney Tissue of a Rat Model with Diabetic Nephropathy
Current Gene Therapy Treatment Considerations of Clinical Physician on Hypertension Management in Asia
Current Hypertension Reviews Synergy of microRNA and Stem Cell: A Novel Therapeutic Approach for Diabetes Mellitus and Cardiovascular Diseases
Current Diabetes Reviews Genetic Variation in the β2-Adrenergic Receptor: Impact on Intermediate Cardiovascular Phenotypes
Current Pharmacogenomics and Personalized Medicine PPAR-γ: Therapeutic Prospects in Parkinson's Disease
Current Drug Targets Metabolic Syndrome, Dyslipidemia and Regulation of Lipoprotein Metabolism
Current Diabetes Reviews Impact on DNA Methylation in Cancer Prevention and Therapy by Bioactive Dietary Components
Current Medicinal Chemistry Lipoprotein-associated Phospholipase A2 and Coronary Heart Disease
Current Pharmaceutical Design Risk of Systemic Autoimmune Diseases with Antiarrhythmic Drugs in Arrhythmia Patients: A Retrospective Cohort Study
Endocrine, Metabolic & Immune Disorders - Drug Targets Bidirectional Nature of Cardiovascular and Kidney Disease
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Oxidative RNA Damage and Neurodegeneration
Current Medicinal Chemistry Obstructive Sleep Apnea and Autoimmune Rheumatic Disease: Is there Any Link?
Inflammation & Allergy - Drug Targets (Discontinued)