Publication Date:
1991-12-20
Description:
The human immunodeficiency virus-1 (HIV-1) trans-activator Tat is an attractive target for the development of antiviral drugs because inhibition of Tat would arrest the virus at an early stage. The drug Ro 5-3335 [7-chloro-5-(2-pyrryl)-3H-1,4-benzodiazepine-2(H)-one], inhibited gene expression by HIV-1 at the level of transcriptional trans-activation by Tat. The compound did not inhibit the basal activity of the promoter. Both Tat and its target sequence TAR were required for the observed inhibitory activity. Ro 5-3335 reduced the amount of cell-associated viral RNA and antigen in acutely, as well as in chronically infected cells in vitro (median inhibition concentration 0.1 to 1 micromolar). Effective inhibition of viral replication was also observed 24 hours after cells were transfected with infectious recombinant HIV-1 DNA. The compound was active against both HIV-1 and HIV-2 and against 3'-azido-3'-deoxythymidine (AZT)-resistant clinical isolates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hsu, M C -- Schutt, A D -- Holly, M -- Slice, L W -- Sherman, M I -- Richman, D D -- Potash, M J -- Volsky, D J -- AI 27397/AI/NIAID NIH HHS/ -- AI 27670/AI/NIAID NIH HHS/ -- AI 29164/AI/NIAID NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1991 Dec 20;254(5039):1799-802.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Virology, Hoffmann-La Roche, Nutley, NJ 07110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1763331" target="_blank"〉PubMed〈/a〉
Keywords:
Antiviral Agents/*pharmacology
;
Benzodiazepinones/*pharmacology
;
Cell Line
;
Gene Products, tat/*antagonists & inhibitors
;
HIV Long Terminal Repeat/drug effects
;
HIV-1/drug effects/genetics/*physiology
;
HIV-2/drug effects/*physiology
;
Humans
;
Kinetics
;
Promoter Regions, Genetic/drug effects
;
Pyrroles/*pharmacology
;
Virus Replication/*drug effects
;
Zidovudine/pharmacology
;
tat 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
