Publication Date:
1995-11-17
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rice, W G -- Supko, J G -- Malspeis, L -- Buckheit, R W Jr -- 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 2nd -- Arthur, L O -- Henderson, L E -- New York, N.Y. -- Science. 1995 Nov 17;270(5239):1194-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Antiviral Drug Mechanisms, PRI/DynCorp., National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7502043" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Antiviral Agents/chemistry/pharmacokinetics/*pharmacology
;
Benzamides/chemistry/pharmacokinetics/*pharmacology
;
Biological Availability
;
Capsid/chemistry/*metabolism
;
*Capsid Proteins
;
Cell Line
;
Disulfides/chemistry/pharmacokinetics/*pharmacology
;
Drug Resistance, Microbial
;
Drug Synergism
;
Gene Products, gag/*antagonists & inhibitors/chemistry
;
HIV-1/*drug effects/physiology
;
Humans
;
Male
;
Mice
;
Molecular Sequence Data
;
*Viral Proteins
;
Zinc Fingers/*drug effects
;
gag Gene Products, Human Immunodeficiency Virus
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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