ADENOSINE N-1-OXIDE INHIBITS VACCINIA VIRUS-REPLICATION BY BLOCKING TRANSLATION OF VIRAL EARLY MESSENGER-RNAS

Adenosine N-1-oxide (ANO) is a potent and highly selective inhibitor o f vaccinia virus replication. We examined the impact of ANO on vaccini a virus macromolecular synthesis during synchronous infection of BSC40 cells, Viral DNA replication and viral late protein synthesis were bl ocked completely by ANO, effects that were attributable to a defect in the expression of viral early genes. Vaccinia virus early proteins we re not synthesized in the presence of ANO, even though vaccinia virus early mRNAs were produced. Cellular protein synthesis was unaffected b y ANO, and virus infection in the presence of the drug did not elicit the normal shutoff of host protein synthesis, Adenosine N-1-oxide trip hosphate (ANO-TP), the predominant metabolite of the drug in vivo, cou ld substitute for ATP in RNA synthesis by purified vaccinia virus RNA polymerase, ANO-TP could support early transcription by purified virio ns if dATP was provided as an energy source, ANO-TP did not inhibit ea rly transcription in the presence of ATP, These findings suggest a nov el antiviral mechanism whereby incorporation of a modified nucleotide into viral mRNAs might selectively block viral gene expression at the level of translation. We believe that ANO merits consideration as an a ntipoxvirus drug for topical treatment of molluscum contagiosum in hum ans.