Meanwell Nicholas A, Serrano-Wu Michael H, Snyder Lawrence B
Department of Chemistry, The Bristol-Myers Squibb Pharmaceutical Research Institute 5 Research Parkway, Wallingford, CT 06492, USA.
Annu Rep Med Chem. 2003;38:213-228. doi: 10.1016/S0065-7743(03)38023-6. Epub 2004 Mar 9.
This chapter focuses on non-HIV antiviral agents. The development of antiviral agents to treat non-HIV infections is largely focused on therapies for the treatment of chronic hepatitis infections B and C. Nucleoside analog continue to be the mainstay of Hepatitis B Virus (HBV) therapeutics. The first small molecule inhibitor of Hepatitis C Virus (HCV), the NS3 protease inhibitor BILN-2061, entered phase 2 clinical trials, producing a striking reduction in viral load in treated individuals. The development of the HCV replicon system and its application to screening for antiviral agents provided tangible benefit with the disclosure of mechanistically and structurally diverse HCV inhibitors. Adefovir dipivoxil has been approved in the United States and the European Union for the treatment of HBV, providing a second small molecule antiviral to add to lamivudine (3TC) and the injectable protein IFNα as the only approved agents for treating HBV infection. The chapter also provides details of the inhibitors of hepatitis B and C virus, the inhibitors of simplex virus and human cytomegalovirus, the inhibitors of respiratory viruses and the inhibitors of West Nile virus and Papilloma virus.
本章重点介绍非HIV抗病毒药物。治疗非HIV感染的抗病毒药物研发主要集中在治疗慢性乙型和丙型肝炎感染的疗法上。核苷类似物仍然是乙型肝炎病毒(HBV)治疗的主要药物。首个丙型肝炎病毒(HCV)小分子抑制剂NS3蛋白酶抑制剂BILN - 2061进入了2期临床试验,使接受治疗的个体病毒载量显著降低。HCV复制子系统的开发及其在抗病毒药物筛选中的应用,随着多种机制和结构各异的HCV抑制剂的披露,带来了切实的益处。阿德福韦酯已在美国和欧盟获批用于治疗HBV,成为继拉米夫定(3TC)和注射用蛋白IFNα之后的第二种小分子抗病毒药物,IFNα是当时唯一获批用于治疗HBV感染的药物。本章还详细介绍了乙型和丙型肝炎病毒抑制剂、单纯疱疹病毒和人巨细胞病毒抑制剂、呼吸道病毒抑制剂以及西尼罗河病毒和乳头瘤病毒抑制剂。