A NOVEL ANTIVIRAL AGENT WHICH INHIBITS THE ENDONUCLEASE OF INFLUENZA-VIRUSES

A novel anti-influenza virus compound, flutimide, was identified in ex tracts of a recently identified fungal species, Delitschia confertaspo ra (F. Pelaez, J. D. Polishook, M. Valldosera, and J. Guarro, Mycotaxo n 50:115-122, 1994). The compound, a substituted 2,6-diketopiperazine, selectively inhibited the cap-dependent transcriptase of influenza A and B viruses and had no effect on the activities of other polymerases . Similar to the 3-substituted 2,4-dioxobutanoic acids, a series of tr anscriptase inhibitors which we described previously (J. Tomassini, H. Selnick, M. E. Davies, M. E. Armstrong, J. Baldwin, M. Bourgeois, J. Hastings, D. Hazuda, J. Lewis, W. McClements, G. Ponticello, E. Radzil owski, G. Smith, A. Tebben, and A. Wolfe, Antimicrob. Agents Chemother , 38:2827-2837, 1994), this inhibitor, which is a natural product, aff ected neither the initiation nor the elongation of influenza virus mRN A synthesis, but it specifically targeted the cap-dependent endonuclea se of the transcriptase. Additionally, the compound was inhibitory to the replication of influenza A and B viruses in cell culture. The sele ctive antiviral properties of this compound further demonstrate the ut ility of influenza virus endonuclease as a target of antiviral agents.