Antiviral activity of copper complexes of isoniazid against RNA tumor viruses

Abstract

The discovery of reverse transcriptase in 1970 [1,2] prompted the search for a specific drug, which could be used to target this key enzyme in order to inhibit the growth and replication of RNA tumor viruses. In 1974, when the zinc metallo-protein nature of reverse transcriptase was reported, Prof. T Ramakrishnan embarked on the idea of using a metal chelating agent — isoniazid, one of the most potent antitubercular drugs — on which research was being carried out in his laboratory for over two decades, to chelate the zinc ion out of the enzyme to render it inactive, thereby inhibiting the viral life cycle. He hypothesized that isoniazid could also prove to be a potent inhibitor of RNA tumor viruses. Here, I will attempt to describe the work that culminated in the use of isoniazid and its copper complexes for the specific inhibition of reverse transcriptase as well as the elucidation of the underlying mechanism of this inhibition.