1887

Abstract

SUMMARY

Several derivatives of benzimidazole were tested for antiviral activity; of these the 1---2′-deoxyriboside of 5,6-dichlorobenzimidazole and the α and β anomers of 5,6-dimethyl-1-(2′-deoxy--ribofuranosyl)benzimidazole inhibited the reproduction of two DNA viruses, herpes simplex virus and polyoma virus; 5,6-dichloro-1-(2′-deoxy---ribofuranosyl)benzimidazole (dDBZ) was the most inhibitory compound. Pretreatment of the host cells with dDBZ, subsequently removed by washing, did not affect the yield of these viruses. dDBZ did not have any direct inactivation effect on herpes simplex virus. Growth curves of herpes virus in the presence of dDBZ indicated that a reduced yield of the virus was obtained after a considerable lag, the first progeny virus being detected 24 hr after infection. Marked inhibition could be demonstrated when the compound was added as late as 15 hr after infection. Attempts to prevent the inhibition by dDBZ by addition of the following compounds failed: deoxyadenosine, deoxyguanosine, deoxycytidine, thymidine, adenine and adenosine. 5,6-Dichlorobenzimidazole, its ribonucleoside (5,6-dichloro-1-(--ribofuranosyl)benzimidazole (DRB)) and the corresponding deoxyribonucleoside (dDBZ) were compared for their relative antiviral activity against a DNA virus (herpes simplex virus) and RNA viruses (three strains of polio virus). All three compounds inhibited herpes simplex virus; the 5,6-dichlorobenzimidazole inhibited two strains of polio virus; and DRB inhibited all three strains of polio virus. dDBZ had the least inhibitory activity for two of the three strains of polio virus and did not inhibit the 1 2 strain of polio virus. dDBZ at a concentration required to inhibit viral replication inhibited the synthesis of RNA and to a lesser extent that of DNA and protein of uninfected green monkey kidney cells.

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1968-12-01
2022-09-25
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