HIV核衣壳蛋白锌指抑制剂作为治疗艾滋病的候选药物。

Inhibitors of HIV nucleocapsid protein zinc fingers as candidates for the treatment of AIDS.

作者信息

Rice W G, Supko J G, Malspeis L, Buckheit R W, Clanton D, Bu M, Graham L, Schaeffer C A, Turpin J A, Domagala J, Gogliotti R, Bader J P, Halliday S M, Coren L, Sowder R C, Arthur L O, Henderson L E

机构信息

Laboratory of Antiviral Drug Mechanisms, PRI/DynCorp., National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA.

出版信息

Science. 1995 Nov 17;270(5239):1194-7. doi: 10.1126/science.270.5239.1194.

DOI:10.1126/science.270.5239.1194

PMID:7502043

Abstract

Strategies for the treatment of human immunodeficiency virus-type 1 (HIV-1) infection must contend with the obstacle of drug resistance. HIV-1 nucleocapsid protein zinc fingers are prime antiviral targets because they are mutationally intolerant and are required both for acute infection and virion assembly. Nontoxic disulfide-substituted benzamides were identified that attack the zinc fingers, inactivate cell-free virions, inhibit acute and chronic infections, and exhibit broad antiretroviral activity. The compounds were highly synergistic with other antiviral agents, and resistant mutants have not been detected. Zinc finger-reactive compounds may offer an anti-HIV strategy that restricts drug-resistance development.

摘要

治疗人类免疫缺陷病毒1型（HIV-1）感染的策略必须应对耐药性这一障碍。HIV-1核衣壳蛋白锌指是主要的抗病毒靶点，因为它们对突变不耐受，并且在急性感染和病毒体组装过程中均必不可少。已鉴定出无毒的二硫键取代苯甲酰胺，其可作用于锌指，使无细胞病毒体失活，抑制急性和慢性感染，并展现出广泛的抗逆转录病毒活性。这些化合物与其他抗病毒药物具有高度协同性，且尚未检测到耐药突变体。锌指反应性化合物可能提供一种限制耐药性发展的抗HIV策略。