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Journal of Pharmacology And Experimental Therapeutics, Vol. 123, Issue 1, 54-62, 1958
Copyright © 1958 by American Society for Pharmacology and Experimental Therapeutics

EFFECTS OF CERTAIN PURINES AND RELATED COMPOUNDS ON VIRUS PROPAGATION

Ariel C. Hollinshead 1 and Paul K. Smith 1

1 Department of Pharmacology, George Washington University School of Medicine, Washington 5, D. C.

Nineteen purines and related compounds were effective in monkey testicular explant tissue cultures against three types of poliomyelitis virus. Of these, 14 were effective in monkey kidney cultures and seven in HeLa cultures. Five compounds were effective against adenovirus, influenza virus and poliomyelitis virus and one inhibited both adenovirus and poliomyelitis virus in this system. Of ten compounds compared in influenza virus-infected chick chorioallantoic membrane tissue cultures and poliomyelitis virus-infected monkey testicular tissue cultures, four compounds were found to be effective in both systems.

Most of the effective drugs were substituted in the same relative positions as guanine.

Virus inhibition was reversed by adenine or guanine or both in most instances. Reversal of inhibition by isoguanine with guanine and by 6-amino-4-methoxy-benzimidazole and adenine appeared to be competitive. Most of the compounds suppressed multiplication of poliomyelitis virus in kidney cultures for at least 24 hours and in testicular cultures for at least 72 hours.

A representative benzimidazole was studied using phase contrast microscopy and found to suppress poliomyelitis virus intracellularly at the beginning of cytopathic stage II.

2-(1-Hydroxybenzyl)-benzimidazole delayed or prevented poliomyelitis virus infection of mice when the compound was given in the diet immediately after inoculation of virus. The compound was found to suppress influenza virus infections of chorioallantoic tissue cultures during the eclipse and latent periods and there was still suppression at later stages.

Submitted on February 14, 1958




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Copyright © 1958 by the American Society for Pharmacology and Experimental Therapeutics.