PERMEATION-ENHANCED PRIMER-DISRUPTING ANTIVIRAL AGENTS

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 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 MODIFICATION UTILIZING A LARGE DATABASE PREVIOUSLY OBTAINED FROM THE EVALUATION OF HUNDREDS OF COMPOUNDS FOR CELLULAR PERMEATION WITH A FLUORESCENT MICROSCOPY TECHNIQUE TO DETERMINE CELLULARLOCALIZATION OF FLUORESCENTLY LABELLED NUCLEIC ACID ANALOGUES. THE COMPOUNDS FOUND ACTIVE IN THE INVITRO TRANCRIPTASE ASSAY WILL SUBSEQUENTLY BE EVALUATED IN TISSUE CULTURE AND, IF WARRANTED, IN VITRO IN AN INFLUENZA ANIMAL MODEL.