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. 1961 Mar 31;113(4):657–682. doi: 10.1084/jem.113.4.657

SPECTRUM AND CHARACTERISTICS OF THE VIRUS INHIBITORY ACTION OF 2-(α-HYDROXYBENZYL)-BENZIMIDAZOLE

Hans J Eggers 1, Igor Tamm 1
PMCID: PMC2137377  PMID: 13725919

Abstract

2-(α-Hydroxybenzyl)-benzimidazole (HBB) inhibited the cytopathic effects of the following enteroviruses: polio 1 to 3; Coxsackie A9; Coxsackie B 1 to 6; and ECHO virus types 1 to 9, 11 to 21, and 24 to 27. The following enteroviruses were not inhibited: Coxsackie A types 7, 11, 13, 16, and 18; and ECHO types 22, 23, and 28. Other HBB-insusceptible viruses were: arbor B and C, reo 1 to 3; adeno 2 to 4; influenza B; para-influenza 2 and 3; mumps; herpes simplex, and vaccinia. HBB had no inactivating effect on viral infectivity, but rather inhibited some intracellular step in the reproductive cycle of susceptible viruses. With all viruses examined, inhibition of viral cytopathic effects appeared to be due to inhibition of virus multiplication. Virus inhibition by HBB was demonstrable in monkey kidney, HeLa, and ERK cells. HBB-susceptible viruses varied quantitatively in their susceptibility to the compound, and different strains of the same virus also exhibited varying susceptibility. No relationship was found between attenuation of polioviruses and their susceptibility to the compound. After passage of HBB-susceptible enteroviruses in the presence of the compound, virus populations with lowered susceptibility to HBB were obtained. At virus inhibitory concentrations, HBB did not affect the morphology of cells, nor the following cellular metabolic activities: oxygen uptake; glucose utilization; lactic acid production; and incorporation of adenosine into RNA, and of alanine into proteins. The rates of multiplication of HeLa and ERK. cells were not significantly altered by HBB at virus inhibitory concentrations.

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Selected References

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  1. CABASSO V. J., JUNGHERR E. L., LEVINE S., MOYER A. W., ROCA-GARCIA M., COX H. R. Assessment of correlation between certain in vitro poliovirus markers and monkey neurovirulence. Br Med J. 1960 Jul 16;2(5193):188–191. doi: 10.1136/bmj.2.5193.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. CHOPPIN P. W., PHILIPSON L. The inactivation of enterovirus infectivity by the sulfhydryl reagent p-chloromercuribenzoate. J Exp Med. 1961 Apr 1;113:713–734. doi: 10.1084/jem.113.4.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. EAGLE H. Amino acid metabolism in mammalian cell cultures. Science. 1959 Aug 21;130(3373):432–437. doi: 10.1126/science.130.3373.432. [DOI] [PubMed] [Google Scholar]
  4. EAGLE H. The minimum vitamin requirements of the L and HeLa cells in tissue culture, the production of specific vitamin deficiencies, and their cure. J Exp Med. 1955 Nov 1;102(5):595–600. doi: 10.1084/jem.102.5.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. HABEL K., LOOMIS L. N. Coxsackie A7 virus and the Russian poliovirus Type 4. Proc Soc Exp Biol Med. 1957 Jul;95(3):597–605. doi: 10.3181/00379727-95-23304. [DOI] [PubMed] [Google Scholar]
  6. HANKS J. H., WALLACE R. E. Relation of oxygen and temperature in the preservation of tissues by refrigeration. Proc Soc Exp Biol Med. 1949 Jun;71(2):196–200. doi: 10.3181/00379727-71-17131. [DOI] [PubMed] [Google Scholar]
  7. HOLLINSHEAD A. C., SMITH P. K. Effects of certain purines and related compounds on virus propagation. J Pharmacol Exp Ther. 1958 May;123(1):54–62. [PubMed] [Google Scholar]
  8. HULLIN R. P., NOBLE R. L. The determination of lacic acid in microgram quantities. Biochem J. 1953 Sep;55(2):289–291. doi: 10.1042/bj0550289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. OVERMAN J. R., TAMM I. Multiplication of vaccinia virus in the chorioallantoic membrane in vitro. Virology. 1957 Feb;3(1):173–184. doi: 10.1016/0042-6822(57)90031-4. [DOI] [PubMed] [Google Scholar]
  10. PARK J. T., JOHNSON M. J. A submicrodetermination of glucose. J Biol Chem. 1949 Nov;181(1):149–151. [PubMed] [Google Scholar]
  11. PELON W. Classification of the "2060" virus as ECHO 28 and further study of its properties. Am J Hyg. 1961 Jan;73:36–54. doi: 10.1093/oxfordjournals.aje.a120164. [DOI] [PubMed] [Google Scholar]
  12. SABIN A. B. Reoviruses. A new group of respiratory and enteric viruses formerly classified as ECHO type 10 is described. Science. 1959 Nov 20;130(3386):1387–1389. doi: 10.1126/science.130.3386.1387. [DOI] [PubMed] [Google Scholar]
  13. TAMM I., BABLANIAN R., NEMES M. M., SHUNK C. H., ROBINSON F. M., FOLKERS K. Relationship between structure of benzimidazole derivatives and selective virus inhibitory activity. Inhibition of poliovirus multiplication and cytopathic effects by 2-(alpha-hydroxybenzyl)-benzimidazole, and its 5-chloroderivative. J Exp Med. 1961 Apr 1;113:625–656. doi: 10.1084/jem.113.4.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. TAMM I., NEMES M. M., OSTERHOUT S. On the role of ribonucleic acid in animal virus synthesis. I. Studies with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole. J Exp Med. 1960 Mar 1;111:339–349. doi: 10.1084/jem.111.3.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. TYRRELL D. A., PARSONS R. Some virus isolations from common colds. III. Cytopathic effects in tissue cultures. Lancet. 1960 Jan 30;1(7118):239–242. doi: 10.1016/s0140-6736(60)90168-9. [DOI] [PubMed] [Google Scholar]

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