Molecular mechanism for the specific inhibition of reverse transcriptase of rous sarcoma virus by the copper complexes of isonicotinic acid hydrazide

Srivastava, Arun and Anton, Abraham and Ramakrishnana, Thekkepat (1978) Molecular mechanism for the specific inhibition of reverse transcriptase of rous sarcoma virus by the copper complexes of isonicotinic acid hydrazide. In: Biochemical Pharmacology, 27 (4). pp. 579-584.

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Abstract

Isonicotinic acid hydrazide (isoniazid), one of the most potent antitubercular drugs, was recently shown, in our laboratory, to form two different complexes with copper, depending upon the oxidation state of the metal ion. Both the complexes have been shown to possess antiviral activity against Rous sarcoma virus, an RNA tumor virus. The antiviral activity of the complexes has been attributed to their ability to inhibit the endogenous reverse transcriptase activity of RSV. More recent studies in our laboratory indicate that both these complexes inhibit both endogenous and exogenous reactions. As low a final concentration as 50 μM of the cupric and the cuprous complexes inhibits the endogenous reaction to the extent of 93 and 75 per cent respectively. Inhibition of the exogenous reaction varies with the templates. The inhibition can be reversed by either β-mercaptoethanol or ethylene-diamine-tetra-acetic acid. The specificity of this inhibition has been ascertained by using a synthetic primer-template, −(dG)not, vert, similar15−(rCm)n, which is highly specific for reverse transcriptases. The inhibition is found to be template specific. The studies carried out, using various synthetic primer-templates, show the inhibition of both the steps of reverse transcription by the copper complexes of isoniazid.

Item Type:	Journal Article
Publication:	Biochemical Pharmacology
Publisher:	Elsevier Science
Additional Information:	Copyright of this article belongs to Elsevier Science.
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	09 Jan 2010 09:55
Last Modified:	19 Sep 2010 05:49
URI:	http://eprints.iisc.ac.in/id/eprint/24278

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