A MAJORITY OF VIRUSES AFFLICTING HUMANS AND LIVESTOCK HAVE RNA GENOMES WHICH ARE BELIEVED TO EXIST IN A DUPLEX A CONFORMATION DURING REPLICATION.

A MAJORITY OF VIRUSES AFFLICTING HUMANS AND LIVESTOCK HAVE RNA GENOMES WHICH ARE BELIEVED TO EXIST IN A DUPLEX A CONFORMATION DURING REPLICATION. SUCH LONG A-FORM DUPLEXES WHICH HAVE BEEN CHARACTERIZED AT ATOMIC RESOLUTION, ARE UNIQUE TO VIRUS-INFECTED CELLS (UNINFECTED CELLS HAVE ONLY SHORT A-FORM STRUCTURES) AND THEREFORE OFFER EXCELLENT WELL-CHARACTERIZED TARGETS FOR PROSPECTIVE ANTIVIRAL AGENTS.TO EXPLOIT THESE VIRUS-SPECIFIC TARGETS SYNTHETIC POLYMERS HAVE BEEN DEVISED WHICH ARE DESIGNED TO INACTIVATE SELECTED A-FORM DUPLEXES WITHOUT CONCOMMITANT ATTACK ON THE B-FORM DUPLEXES COMPRISING THE INFECTED ORGANISM'S GENOME. CALCULATIONS SUGGEST THAT A SINGLE SUCH A-DIRECTED ANTI-GENEMAY BE EFFECTIVE AGAINST MOST RNA VIRUSES. THE APPLICANT PROPOSES SUPPORT FOR CONTINUATION OF A PROOF-OF-CONCEPT STUDY WHICH INCLUDES: (A) ASSEMBLY OF A SERIES OF SIMPLE PROTOTYPE ANTI-GENES, (B) ASSESSMENT OF THEIR STRENGTH AND SPECIFICITY OF BINDING TO BOTH TARGET AND NONTARGET POLYNUCLEOTIDES; AND, (C) ASSESSMENT OF THE BIOLOGICAL CONSEQUENCES OF SUCH BINDING. THE EXPECTATION IS THAT THESEPROTOTYPE ANTI-GENES WILL BE FOUND TO BIND TO THEIR SPECIFICTARGET DUPLEXES BUT NOT TO POLYNUCLEOTIDES DIFFERING IN SEQUENCE OR CONFORMATION, AND THAT SUCH BINDING WILL RENDER THE TARGET SEQUENCES GENETICALLY INACTIVE. SUCH A RESULT WILL VERIFY THAT THE PREDICTED MOLECULAR INTERACTIONS OCCUR WITH THE REQUISITE FORM AND SEQUENCE SPECIFICITIES, THEREBY LAYING A RIGOROUS FOUNDATION FOR SUBSEQUENT DEVELOPMENT OF A ANTI-GENES DESIGNED FOR USE AGAINST A BROAD RANGE OF RNA VIRUSES. BASED ON THE CURRENT ANTIBIOTICS MARKET AND THE RELATIVE FREQUENCIES OF BACTERIAL VS. VIRAL INFECTIONS IT ISPROJECTED THAT A SAFE AND EFFECTIVE BROAD-SPECTRUM ANTIVIRALAGENT WILL HAVE WORLD-WIDE MARKET.