The research describes an approach to an orally active agent against both Influenza A and B. Influenza virus transcription occurs by a unique mechanism. Both dinucleoside monophosphate analogues of the type ApG and analogues of the MRNA cap structure of the type 7-methyl-GMP have been found to inhibit viral transcription in vitro, but all of these compounds are inactive in vivo. The first goal is to render these compounds cell permeable by chemical modifications utilizing a large database previously obtained from the evaluation of hundreds of compounds for cellular permeation with a fluorescent microscopy technique to determine cellular localization of fluorescently labelled nucleic acid analogues. The compounds found active in the in vitro transcriptase assay will subsequently be evaluated in tissue culture and, if warranted, in vitro in an influenza animal model.Awardee's statement of the potential commercial applications of the research:Influenza is a major health concern in the U. S. with 25 million cases occurring each year. Current therapeutics have severe shortcomings and there is clearly an urgent need to develop more efficacious therapies. The present approach offers a promising avenue for the development of active agents against influenza, and it has potential applications in other viral diseases as well.National Institute of Allergy and Infectious Diseases (NIAID)
