Erik Helgstrand

Inhibition of Influenza Virus Ribonucleic Acid Polymerase by Ribavirin Triphosphate

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.

The effect of pyrophosphate analogues on influenza virus RNA polymerase and influenza virus multiplication

SummaryAnalogues 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 µm. The inhibition was dependent on the type of divalent cation present in the assay. PFA at a concentration of 400 µm also inhibited the influenza virus plaque formation by 90 per cent.

Pyridines Affecting FFA Mobilization In Vivo

In man an intimate correlation exists between clinical manifestations of atherosclerosis and raised levels of lipids in blood plasma. An increased mobilization of FFA into plasma, which may be caused, e.g. by emotional stress (1, 2, 3), could be one of several factors causing high plasma lipid levels (3, 4). One approach to the prevention and treatment of atherosclerotic disease would be to lower plasma lipid levels by means of drugs able to inhibit FFA mobilization. Nicotinic acid is such an agent (5, 6). Long term administration of this drug lowers elevated levels of triglycerides and cholesterol in plasma (7). However, nicotinic acid has such disadvantages as short duration of action (8) and certain side effects such as flush and gastro-intestinal irritation.