药物化学概述：大环肽类丙型肝炎病毒HCV NS3/4A蛋白酶抑制剂

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.

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