Ribavirin 5′-triphosphate (RTP), derived from the broad-spectrum antiviral compound ribavirin (Virazole), can selectively inhibit influenza virus ribonucleic acid polymerase in a cell-free assay. Ribavirin and its 5′-monophosphate have no effect on the polymerase. The inhibition is competitive with respect to adenosine 5′-triphosphate and guanosine 5′-triphosphate. RTP also inhibits ApG- and GpC-stimulated influenza virus ribonucleic acid polymerase. Since ribavirin is phosphorylated in the cell, the inhibition of influenza multiplication in the cell may also be caused by RTP.

Trisodium phosphonoformate selectively inhibits cell-free DNA polymerase activity induced by herpesvirus. The new inhibitor has an antiviral effect on herpes simplex virus types 1 and 2, pseudorables virus, and infectious bovine rhinotracheitis virus in cell culture. It has a good therapeutic activity against cutaneous herpes simplex virus infection in guinea pigs.

A rapid method for determining the concentration of ribonucleoside triphosphates in cell cultures is described. The pool sizes of the ribonucleoside triphosphates in uninfected MDCK cells were found to be, 0.28-0.59 mM CTP, 0.96-1.6 mM UTP, 6.5-7.8 mM ATP, and 1.1-1.4 mM GTP, depending on the condition of the cell-monolayer. Infection of MDCK cells with influenza A strains Victoria 3/75 x-47 or WSN resulted in insignificant changes in the ribonucleoside triphosphate concentrations. Treatment of infected and non-infected MDCK cells with ribavirin caused a decrease of 60 per cent in the GTP pool.

No abstract

Analogues of pyrophosphate have been tested as inhibitors of influenza virus-RNA polymerase activity in cell-free assays. The most active compound, phosphonoformic acid (PFA), reduced the polymerase activity to 50 per cent at a concentration of 20 muM. The inhibition was dependent on the type of divalent cation present in the assay. PFA at a concentration of 400 muM also inhibited the influenza virus plaque formation by 90 per cent.