Anti-poxvirus Activity of Rifampicin associated with Hydrazone Side Chain

Abstract

RIFAMPICIN¹ inhibits the replication of vaccinia virus in infected cells in vitro when added at 100 µg/ml. immediately after infection^3,4 or at a late stage of the virus latent period⁴. In the presence of the drug the translation of late viral mRNA spacies was found to be markedly inhibited 8 h after infection⁵; the rate of late viral protein synthesis declined⁶; the synthesis of the particulate viral RNA polymerase molecules, induced late in infection, was prevented⁷; and the assembly of virions was affected^8,9. Rifampicin did not affect the synthesis of viral mRNA molecules nor their association with ribosomos to form polyribosomes⁵. The inability of rifampicin to inhibit in vitro the activity of the three different species of poxvirus specific DNA dependent RNA polymerases⁷ suggested that the mode of antiviral activity of rifampicin differed from its antimicrobial activity. The latter was attributed¹⁰ to the macrocyclic ring of the rifamycin SV molecule which binds to the microbial DNA dependent RNA polymerase and inhibits the initiation of RNA synthesis. Using Shope fibroma virus (SFV), a poxvirus which causes localized tumours in rabbits^11–13, and several rifamycin SV derivatives, we have obtained results which indicate that the anti-poxvirus activity resides in the hydrazone side chain of rifampicin.