Griseochelin methyl ester, a new polyether derivative with antiviral activity

The methylester of griseochelin (1) is a new chemically-made antiviral derivate of the antibiotic griseochelin isolated from fermentations of Streptomyces griseus. It belongs to the polyether group and possesses antiviral activity against enveloped RNA and DNA viruses cultivated in chicken embryo cells (CEC), namely influenzavirus A/WSN, vesicularstomatitis virus (Indiana), vaccinia virus (Lister) and herpes simplex hominis virus type 1 (Kupka). The methylester of griseochelin failed to show virucidal effects on extracellular influenza vacciniavirus particles or to influence virus adsorption and penetration processes. The antibiotic in concentrations of 125-15 micrograms/ml inhibited the virus-induced cytopathic effect of the above mentioned viruses and caused over 90 per cent plaque reduction. Addition of 1 during a one-step growth cycle of influenzavirus A at 4 and 6 h p.i. resulted in complete suppression of virus multiplication at the control niveau of the virus yield accumulated to the same time point. A partial reversibility of the antiviral action against influenzavirus A could be achieved. Coxsackie A9 virus growth in human fibroblast cells was not affected by the inhibitor. Electron-optical observations showed a failure of the formation of the viral capside proteins of HSV type 1 at the second halftime of the replication cycle in CEC-infected and 1-treated cultures.