摘要
丙型肝炎病毒(HCV)是丙型肝炎传染病的病原体,主要影响肝脏,就其严重性而言,一般会持续几周或直至终身。HCV的RNA基因组长9.6 kb,编码约3000个氨基酸的多聚蛋白,必须同时经过宿主和病毒蛋白酶的处理分别形成结构型(S)和非结构型(NS)蛋白。在此我们关注带有活化因子NS4A的丝氨酸蛋白酶NS3,即NS3/4A,一直被视为抗HCV治疗的最有吸引力的靶点之一。虽然没有可用的HCV疫苗,但仅是抗病毒药物就能够治愈约90%的患有丙型肝炎感染的病人。但另一方面,这些药物的疗效可能会由于过快的用药和交叉耐药性而受到阻碍。到目前为止,所有的HCV NS3/4A抑制剂主要是基于肽段的化合物,而这些化合物都源于NS3/4A底物的裂解产物。特别是大环肽已迅速成为一个经典的用于治疗HCV感染的NS3/4A蛋白酶抑制剂。本文综述了大环肽抗HCV NS3/4A蛋白酶的发展过程,以及临床上一些开发自线性肽段的重要抑制剂,这些抑制剂都是在过去的12年(2003-2015年)中通过所有的途径发现的,包括实验室合成的方法,虚拟筛选和基于结构的分子对接结构研究。我们强调设计背后的原理、构效关系研究,以及抑制剂的作用机制和大环肽对细胞的影响。
关键词: Hepatitis C virus
Current Medicinal Chemistry
Title:Macrocyclic Hepatitis C Virus NS3/4A Protease Inhibitors: An Overview of Medicinal Chemistry
Volume: 23 Issue: 29
Author(s): Thanigaimalai Pillaiyar, Vigneshwaran Namasivayam, Manoj Manickam
Affiliation:
关键词: Hepatitis C virus
摘要: Hepatitis C virus (HCV) is a causative agent of hepatitis C infectious disease that primarily affects the liver, ranging in severity from a mild illness lasting a few weeks to a lifelong illness. The 9.6 kb RNA genome of HCV encodes approximately 3000 amino acid polyprotein that must be processed by host and viral proteases into both structural (S) and non-structural (NS) proteins, respectively. Targeting the serine protease NS3 with an activating factor NS4A, i.e., NS3/4A has been considered as one of the most attractive targets for the development of anti-HCV therapy. Although there is no vaccine available, antiviral medicines cure approximately 90% of the persons with hepatitis C infection. On the other hand, efficacy of these medications can be hampered due to the rapid drug and cross resistances. To date, all developed HCV NS3/4A inhibitors are mainly peptide-based compounds derived from the cleavage products of substrate. Specifically macrocyclic peptidomimetics have rapidly emerged as a classical NS3/4A protease inhibitors for treating the HCV infection. This review highlights the development of macrocyclic anti-HCV NS3/4A protease, as well as clinically important inhibitors developed from linear peptides, discovered during the last 12 years (2003-2015) from all sources, including laboratory synthetic methods, virtual screening and structure-based molecular docking studies. We emphasize the rationale behind the design, study of structure-activity relationships, and mechanism of inhibitions and cellular effect of the macrocyclic inhibitors.
Export Options
About this article
Cite this article as:
Thanigaimalai Pillaiyar, Vigneshwaran Namasivayam, Manoj Manickam , Macrocyclic Hepatitis C Virus NS3/4A Protease Inhibitors: An Overview of Medicinal Chemistry, Current Medicinal Chemistry 2016; 23 (29) . https://dx.doi.org/10.2174/0929867323666160510122525
DOI https://dx.doi.org/10.2174/0929867323666160510122525 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Omacetaxine as an Anticancer Therapeutic: What is Old is New Again
Current Pharmaceutical Design Enzyme Mediated Baeyer-Villiger Oxidations
Current Organic Chemistry Characterization of Heme Oxygenase in Adult Rodent Platelets
Current Neurovascular Research In Vitro and In Vivo Models of Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets A Rare Cause of Upper Gastrointestinal Bleeding in Children: Gastric Schwannoma
Current Pediatric Reviews Meet Our Associate Editor:
Current Molecular Medicine Construction of an M1GS Ribozyme for Targeted and Rapid mRNA Cleavage; Application on the Ets-2 Oncogene
Medicinal Chemistry New Perspectives on Acyl Glucuronide Risk Assessment in Drug Discovery: Investigation of In vitro Stability, In situ Reactivity, and Bioactivation
Drug Metabolism Letters Induction of Protective Immunity Against Microbial Challenge by Targeting Antigens Expressed by Probiotic Bacteria to Mucosal Dendritic Cells
Current HIV Research Equipping CAR-Modified T Cells with a Brake to Prevent Chronic Adverse Effects
Current Gene Therapy Nitric Dioxide as Biologically Important Radical and its Role in Molecular Mechanism of Pancreatic Inflammation
Current Pharmaceutical Analysis Cross-Talk Between the Androgen Receptor and the Phosphatidylinositol 3-Kinase/Akt Pathway in Prostate Cancer
Current Cancer Drug Targets Targeting Transcription Factors for Cancer Gene Therapy
Current Gene Therapy Specific Targeting of Engineered Nanoparticles to Activated Macrophages
Current Nanoscience ACKNOWLEDGEMENTS TO CONTRIBUTORS (2015):
Recent Patents on Inflammation & Allergy Drug Discovery Kynurenine Pathway in Schizophrenia: Pathophysiological and Therapeutic Aspects
Current Pharmaceutical Design Mesenchymal Stromal Cells from Umbilical Cord Blood
Current Stem Cell Research & Therapy Pancreas Development and β-Cell Differentiation of Embryonic Stem Cells
Current Medicinal Chemistry Endocrinological Aspects of Proteinuria and Podocytopathy in Diabetes: Role of the Aldosterone/Mineralocorticoid Receptor System
Current Diabetes Reviews Small Molecule Inhibitors of Stat3 Signaling Pathway
Current Cancer Drug Targets