Antiviral Action of 2-(α-Hydroxybenzyl)-Benzimidazole (HBB)

  • Hans J. Eggers
Part of the NATO ASI Series book series (NSSA, volume 73)


Since 1952 the antiviral activity of benzimidazoles has been studied extensively (1). A major stimulus during this work has been the central finding that virus-inhibiting activity and cell toxicity of chemical derivatives of benzimidazoles may vary independently (2). The introduction of 2-(α-hydroxybenzyl)-benzimidazole (HBB) as an antiviral agent marked a most important step of the investigations on selective inhibition of viral replication (3,4). It was found that HBB inhibits multiplication of poliovirus 2 in monkey kidney cell culture at concentrations which caused no microscopic changes in the cells. On the other hand, influenza virus multiplication remained unaffected (4).


Antiviral Action Newcastle Disease Virus Monkey Kidney Cell Viral Polypeptide Influenza Virus Multiplication 
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  1. 1.
    I. Tamm, K. Folkers, and F. L. Horsfall, Jr., Inhibition of influenza virus multiplication by 2,5-dimethylbenzimidazole. Yale J. Biol. Med. 24: 559 (1952).PubMedGoogle Scholar
  2. 2.
    I. Tama, Selective inhibition of virus multiplication by synthetic chemicals. Bull. N.Y. Acad. Med., 31: 537 (1955).Google Scholar
  3. 3.
    A. C. Hollinshead, and P. K. Smith, Effects of certain purines and related compounds on virus propagation. J. Pharmacol. Exp. Ther. 123: 54 (1958).PubMedGoogle Scholar
  4. 4.
    I. Tamm, and M. M. Nemes, Selective inhibition of poliovirus multiplication. J. Clin. Invest. 38: 1047 (1959).Google Scholar
  5. 5.
    H. J. Eggers, and I. Tamm, Spectrum and characteristics of the virus inhibitory action of 2-(a-hydroxybenzyl)-benzimidazole. J. Exp. Med. 113: 657 (1961).PubMedCrossRefGoogle Scholar
  6. 6.
    H. J. Eggers, and I. Tamm, 2-(a-Hydroxybenzyl)benzimidazole (HBB) as an aid in virus classification. Virology 13: 545 (1961).PubMedCrossRefGoogle Scholar
  7. 7.
    I. Tamm, and L. A. Caliguiri, 2-(a-Hydroxybenzyl)benzimidazole and related compounds, in: The International Encyclopedia of Pharmacology and Therapeutics, vol. 1, D. J. Bauer, ed., Pergamon, Oxford, New York, pp. 115 (1972).Google Scholar
  8. 8.
    H. J. Eggers, Benzimidazoles. Selective inhibitors of picornavirus replication in cell culture and in the organism, in: Chemotherapy of Viral Infections, P. E. Came, and L. A. Caliguiri, eds., Handb. Exp. Pharm., Vol. 61. Springer, Berlin, Heidelberg, New York, pp. 377 (1982).Google Scholar
  9. 9.
    G. Siegl, and H. J. Eggers, Failure of guanidine and 2-(a-hydroxybenzyl)-benzimidazole to inhibit replication of hepatitis A virus in vitro, J. Gen. Virol. 61: 111 (1982).PubMedCrossRefGoogle Scholar
  10. 10.
    H. J. Eggers, and I. Tamm, On the mechanism of selective inhibition of enterovirus multiplication by 2-(a-hydroxybenzyl)-benzimidazole. Virology 18: 426 (1962).CrossRefGoogle Scholar
  11. 11.
    I. Tamm, R. Bablanian, M. M. Nemes, C. H. Shunk, F. M. Robinson, and K. Folkers, Relationship between structure of benzimidazole derivatives and selective virus inhibitory activity, J. Exp. Med. 113: 625 (1961).PubMedCrossRefGoogle Scholar
  12. 12.
    I. Tamm, H. J. Eggers, R. Bablanian, A. F. Wagner, and K. Folkers, Structural requirements of selective inhibition of enteroviruses by 2-(a-hydroxybenzyl)benzimidazole and related compounds. Nature 223: 785 (1969).PubMedCrossRefGoogle Scholar
  13. 13.
    I. Tamm, and H. J. Eggers, Differences in the selective virus inhibitory action of 2-(a-hydroxybenzyl)-benzimidazole and guanidine HC1, Virology 18: 439 (1962).PubMedCrossRefGoogle Scholar
  14. 14.
    H. J. Eggers, E. Reich, and I. Tamm, The drug-requiring phase in the growth of drug-dependent enteroviruses, Proc. Natl. Acad. Sci. USA 50: 183 (1963).PubMedCrossRefGoogle Scholar
  15. 15.
    S. Halperen, H. J. Eggers, and I. Tamm, Evidence for uncoupled synthesis of viral RNA and viral capsids, Virology 24: 36 (1964).PubMedCrossRefGoogle Scholar
  16. 16.
    L. A. Caliguiri, H. J. Eggers, N. Ikegami, and I. Tamm, A single-cell study of chemial inhibition of enterovirus multiplicaton, Virology 27: 551 (1965).PubMedCrossRefGoogle Scholar
  17. 17.
    H. J. Eggers, and E. Weidner, Effect of 2-(a-hydroxybenzyl)-benzimidazole and guanidine on the uncoating of echovirus 12, Nature 27: 952 (1970).CrossRefGoogle Scholar
  18. 18.
    H. J. Eggers, Selective inhibition of uncoating of echovirus 12 by rhodanine, Virology 78: 241 (1977).PubMedCrossRefGoogle Scholar
  19. 19.
    S. E. Luria, J. E. Darnell, Jr., D. Baltimore, and A. Campbell, in: General Virology, 3rd ed., J. Wiley and Sons, New York, Santa Barbara, Chichester, Brisbane, Toronto (1978).Google Scholar
  20. 20.
    H. J. Eggers, and I. Tamm, Inhibition of enterovirus ribonucleic acid synthesis by 2-(0.-hydroxybenzyl)benzimidazole, Nature 197: 1327 (1963).CrossRefGoogle Scholar
  21. 21.
    D. Baltimore, and R. M. Franklin, Preliminary data on a virus-specific enzyme system responsible for the synthesis of viral RNA, Biochem. Biophys. Res. Commun. 9: 388 (1962).PubMedCrossRefGoogle Scholar
  22. 22.
    D. Baltimore, H. J. Eggers, R. M. Franklin, and I. Tamm, Poliovirus-induced RNA polymerase and the effects of virus-specific inhibitors on its production, Proc. Natl. Acad. Sci. USA 49: 843 (1963).PubMedCrossRefGoogle Scholar
  23. 23.
    H. J. Eggers, D. Baltimore, and I. Tamm, The relation of protein synthesis to formation of polio-virus RNA polymerase, Virology 21: 281 (1963).PubMedCrossRefGoogle Scholar
  24. 24.
    L. A. Caliguiri, and I. Tamm, Action of guanidine on the replication of poliovirus RNA, Virology 35: 408 (1968).PubMedCrossRefGoogle Scholar
  25. 25.
    L. A. Caliguiri, and I. Tamm, Distribution and translation of poliovirus RNA in guanidine-treated cells, Virology 36: 223 (1968).PubMedCrossRefGoogle Scholar
  26. 26.
    D. R. Tershak, Inhibition of poliovirus polymerase by guanidine in vitro, J. Virol. 41: 313 (1982).PubMedGoogle Scholar
  27. 27.
    D. R. Tershak, F. H. Yin, and B. D. Korant, Guanidine, in: Chemotherapy of Viral Infections, P.E. Came, and L.A. Caliguiri, eds., Handb. Exp. Pharm., Vol. 61, Springer, Berlin, Heidelberg, New York, pp. 343 (1982).Google Scholar
  28. 28.
    R. R. Rueckert, T. J. Matthews, O. M. Kew, M. Pallansch, C. McLean, and D. Omilianowski, Synthesis and processing of picornaviral polyprotein, in: Molecular Biology of Picornaviruses, R. Perezz-Bercoff, ed., Plenum, New York, pp. 113 (1979).CrossRefGoogle Scholar
  29. 29.
    P. D. Cooper, B. B. Wentworth, and D. McCahon, Guanidine inhibition of poliovirus: a dependence of viral RNA synthesis on the configuration of structural protein, Virology 40: 486 (1970).CrossRefGoogle Scholar
  30. 30.
    B. D. Korant, Poliovirus coat protein as the site of guanidine action, Virology 81: 17 (1977).CrossRefGoogle Scholar
  31. 31.
    Th. Adrian, B. Rosenwirth, and H. J. Eggers, Isolation and characterization of temperature-sensitive mutants of echovirus 12, Virology 99: 329 (1979).PubMedCrossRefGoogle Scholar
  32. 32.
    H. J. Eggers, and I. Tamm, Antiviral chemotherapy, Annu. Rev. Pharmacol. 6: 231 (1966).PubMedCrossRefGoogle Scholar
  33. 33.
    I. Tamm, and H. J. Eggers, Unique susceptibility of enteroviruses to inhibition by 2-(a-hydroxybenzyl)benzimidazole and derivatives, in: 2nd International Symposium of Chemotherapy, Part. II, H. P. Kuemmerle, P. Preziosi, and P. Rentchnick, eds., Karger, Basel New York, pp. 88 (1963).Google Scholar
  34. 34.
    H. J. Eggers, Discussion to: Genetic recombination with Newcastle disease virus, poliovirus, and influenza (by G. K. Hirst). Cold Spring Harbor Symp. Quant. Biol. 27: 309 (1962).Google Scholar
  35. 35.
    H. J. Eggers, and I. Tamm, A variant of coxsackie A9 virus which requires 2-(0L-hydroxybenzyl)-benzimidazole (HBB) for optimal growth (Abstr.), in: VIIIth Int. Congr. Microbiol. p. 85 (1962).Google Scholar
  36. 36.
    H. J. Eggers, and I. Tamm, Drug dependence of enteroviruses: variants of coxsackie A9 and ECHO 13 viruses that require 2-(a-hydroxybenzyl)-benzimidazole for growth, Virology 20: 62 (1963).CrossRefGoogle Scholar
  37. 37.
    H. J. Eggers, and I. Tamm, Coxsackie A9 virus: mutation from drug dependence to drug independence, Science 148: 97 (1965).PubMedCrossRefGoogle Scholar
  38. 38.
    B. K. Nottay, O. M. Kew, M. H. Hatch, J. T. Heyward, and J. F. Obijeski, Molecular variation of type 1 vaccine-related and wild polioviruses during replication in humans, Virology 108: 405 (1981).PubMedCrossRefGoogle Scholar
  39. 39.
    C. E. Cords, and J. J. Holland, Replication of poliovirus RNA induced by heterologous virus, Proc. Natl. Acad. Sci. USA 51: 1080 (1964).PubMedCrossRefGoogle Scholar
  40. 40.
    J. J. Holland, and C. E. Cords, Maturation of polio-virus RNA with capsid protein coded by heterologous enteroviruses, Proc. Natl. Acad. Sci. USA 51: 1082 (1964).PubMedCrossRefGoogle Scholar
  41. 41.
    E. Wecker, and G. Lederhilger, Curtailment of the latent period by double-infection with polioviruses, Proc. Natl. Acad. Sci. USA 52: 246 (1964).PubMedCrossRefGoogle Scholar
  42. 42.
    V. I. Agol, and G. A. Shirman, Interaction of guanidine-sensitive and guanidine-dependent variants of poliovirus in mixedly infected cells, Biochem. Biophys. Res. Commun. 17: 28 (1964).CrossRefGoogle Scholar
  43. 43.
    N. Ikegami, H. J. Eggers, and I. Tamm, Rescue of drug-requiring and drug-inhibited enteroviruses, Proc. Natl. Acad. Sci. USA 52: 1419 (1964).PubMedCrossRefGoogle Scholar
  44. 44.
    R. Bablanian, H. J. Eggers, and I. Tamm, Inhibition of enterovirus cytopathic effects by 2-(a-hydroxybenzyl)-benzimidazole, J. Bacteriol. 91: 1289 (1966).PubMedGoogle Scholar
  45. 45.
    B. Rosenwirth, and H. J. Eggers, Echovirus 12-induced host cell shutoff is prevented by rhodanine, Nature 267: 370 (1977).PubMedCrossRefGoogle Scholar
  46. 46.
    B. Rosenwirth, and H. J. Eggers, Structure and replication of echovirus type 12. 2. Viral polypeptides synthesized in the infected cell, Eur. J. Biochem. 92: 61 (1978).PubMedCrossRefGoogle Scholar
  47. 47.
    R. Bablanian, H. J. Eggers, and I. Tamm, Studies on the mechanism of poliovirus-induced cell damage. I. The relation between poliovirus-induced metabolic and morphological alterations in cultured cells, Virology 26: 100 (1965).PubMedCrossRefGoogle Scholar
  48. 48.
    R. Bablanian, H. J. Eggers, and I. Tamm, Studies on the mechanism of poliovirus-induced cell damge. II. The relation between poliovirus growth and virus-induced morphological changes in the cells, Virology 26: 114 (1965).PubMedCrossRefGoogle Scholar
  49. 49.
    S. Dales, H. J. Eggers, I. Tamm, and G. E. Palade, Electron microscopic study of the formation of poliovirus, Virology 26: 379 (1965).PubMedCrossRefGoogle Scholar
  50. 50.
    K. Bienz, D. Egger, Y. Rasser, and W. Bossart, Kinetics and location of poliovirus macromolecular synthesis in correlation to virus-induced cytopathology, Virology 100: 390 (1980).PubMedCrossRefGoogle Scholar
  51. 51.
    H. J. Eggers, Successful treatment of enterovirusinfected mice by 2-(a-hydroxybenzyl)-benzimidazole and guanidine, J. Exp. bled. 143: 1367 (1976).CrossRefGoogle Scholar
  52. 52.
    E. C. Herrmann, Jr., J. A. Herrmann, and D. C. DeLong, Comparision of the antiviral effects of substituted benzimidazoles and guanidine in vitro and in vivo, Antiviral Research 1: 301 (1981).CrossRefGoogle Scholar
  53. 53.
    R. J. Phillpotts, D. C. DeLong, J. Wallace, R. W. Jones, S. E. Reed, and D. A. J. Tyrrell, The activity of enviroxime against rhinovirus infection in man, Lancet I: 1342 (1981).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Hans J. Eggers
    • 1
  1. 1.Institut für VirologieUniversität zu KölnKöln 41Germany

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