Inhibition of herpes simplex virus type 2 replication in vitro by 1-N-pentadecanoyl-3'-N-trifluoroacetyl kanamycin A

The in vitro antiviral activity as well as the mechanism of action of a new antiviral agent, a kanamycin analogue, 1-N-pentadecanoyl-3'-N-trifluoroacetyl kanamycin A (PTKA) against herpes simplex virus type 2 (HSV-2) was investigated. The drug showed excellent antiviral action with negligible cytotoxic effect on the culture cells. Based on plaque reduction assays the 50% inhibitory dose (ID50) of the drug was 1 microgram/ml, and at 20 micrograms/ml plaque formation was totally suppressed. The compound inhibited viral protein synthesis in infected cells without affecting RNA and DNA synthesis, when added to the cultures after virus adsorption. Moreover, pretreatment of the cells with PTKA before HSV-2 infection, increased the antiviral activity significantly. Dot-blot hybridization analysis revealed that the drug reduced the level of immediate early viral mRNA if applied before infection. There was no detectable action at the level of virus adsorption, penetration or uncoating. These results indicate that PTKA exerted its antiviral action at the early stage of viral replication as well as at the level of viral protein synthesis.