Advertisement

Design of Anti-Viral Agents Other than Nucleoside Analogues

  • Stanley M. Roberts
Part of the NATO ASI Series book series (NSSA, volume 143)

Abstract

It is generally accepted that, by the very nature of the invading organisms and their interactions with the host, the search for anti-viral compounds is going to be much more difficult than the corresponding searches for anti-bacterial and anti-fungal substances. Having accepted this situation it is interesting to note that over the past ten years the only compounds to emerge as serious contenders for a place as commercially important anti-bacterials are more β-lactams (e.g. thienamycin, aztrenonam) and more nalidixic acid analogues (e.g. ofloxacin). The situation with regard to the establishment of new anti-fungal agents is even simpler; only imidazole derivatives (e.g. fluconazole) related to ketoconazole have emerged as compounds that may take up a noteworthy position in the market place. Not surprisingly, therefore, the establishment of promising anti-viral agents over the same time period has been painfully slow. Nevertheless acyclovir and various prodrugs, as well as some other nucleoside analogues with potent anti-viral properties, have been discovered and will be discussed in other Chapters. The opportunities afforded by inhibiting virally-coded enzymes with nucleoside analogues are well recognised and a number of interesting anti-viral agents have been ‘designed’ using the information (viz. mode of action, metabolism, etc.) gained from the leading compounds.

Keywords

Influenza Virus Nucleoside Analogue Antiviral Agent Genital Herpes Ribonucleotide Reductase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    N.L. Shipkowitz, R.R. Bower, R.N. Appell, C.W. Nordeen, L.R. Overby, W.R. Roderick, J.B. Schleicher, and A.M. von Esch, Suppression of herpes simplex virus infection by phosphonoacetic acid, Appl. Microbiol. 26:264 (1973);PubMedGoogle Scholar
  2. 1a.
    E. Helgstrand, B. Eriksson, N.G. Johansson, B. Lannerö, A. Larsson, A. Misiorny, J.O. Norén, B. Sjöberg, K. Stenberg, G. Stening, S. Stridh, B. Oberg, S. Alenius, and L. Philipson, Trisodium phosphonoformate, a new antiviral compound, Science 201:819 (1978).PubMedCrossRefGoogle Scholar
  3. 2.
    P.A. Cload and D.W. Hutchinson, The inhibition of the RNA polymerase activity of influenza virus A by pyrophosphate analogues, Nucleic Acids Res. 11:5621 (1983).PubMedCrossRefGoogle Scholar
  4. 3.
    E. Helgstrand and B. Oberg, Enzymatic targets in virus chemotherapy, Antibiotics Chemother. 27:22 (1980) and references therein.Google Scholar
  5. 4.
    B. Eriksson and B. Oberg, Phosphonoformate and phosphonoacetate, in: “Antiviral Drugs and Interferon: The Molecular Basis of Their Activity”, Y. Becker, ed., Martinus Nijhoff, Boston, p. 127 (1984).CrossRefGoogle Scholar
  6. 5.
    D.W. Hutchinson, M. Naylor, and G. Semple, Inhibition of viral nucleic acid synthesis by analogues of inorganic pyrophosphate, Chem. Scripta 26:91 (1986).Google Scholar
  7. 6.
    D.W. Hutchinson and S. Masson, The antiviral potential of compounds containing the thiophosphonyl group, I.R.C.S. Med. Sci. 14:176 (1986).Google Scholar
  8. 7.
    G. Streissle, A. Paessens, and H. Oediger, New antiviral compounds, in: “Advances in Virus Research”, K. Maramorosch, F.A. Murphy and A.J. Shatlain, eds., Academic Press, Orlando (1985).Google Scholar
  9. 8.
    L. Vrang and B. Oberg, PPi analogs as inhibitors of human T-lymphotropic virus type III reverse transcriptase. Antimicrob. Agents Chemother. 29:867 (1986).PubMedGoogle Scholar
  10. 9.
    P.A. Cload and D.W. Hutchinson, The inhibition of RNA polymerase activity of influenza virus A by pyrophosphate analogues, Nucleic Acids Res. 11:5621 (1983);PubMedCrossRefGoogle Scholar
  11. 9a.
    D.W. Hutchinson, M. Naylor, G. Semple, and P.A. Cload, Pyrophosphate analogues as inhibitors of viral polymerases, Biochem. Soc. Trans. 13:752 (1985).Google Scholar
  12. 10.
    G.D. Diana, E.S. Zalay, U.J. Salvador, F. Pancic, and B. Steinberg, Synthesis of some phosphonates with antiherpetic activity, J. Med. Chem. 27:691 (1984).PubMedCrossRefGoogle Scholar
  13. 11.
    M. Baba and S. Shigeta, Antiviral activity of glycyrrhizin against varicella-zoster virus in vitro, Antiviral Res. 7:99 (1987).PubMedCrossRefGoogle Scholar
  14. 12.
    D.J. Dargan and J.H. Subak-Sharpe, The antiviral activity against herpes simplex virus of the triterpenoid compounds carbenoxolone sodium and cicloxolone sodium. J. Antimicrob. Chemother. 18 (Suppl. B):185 (1986);PubMedGoogle Scholar
  15. 12a.
    D.J. Dargan and J.H. Subak-Sharpe, The effect of triterpenoid compounds on uninfected and herpes simplex virus-infected cells in culture. I. Effect on cell growth, virus particles and virus replication, J. Gen. Virol. 66:1771 (1985).PubMedCrossRefGoogle Scholar
  16. 13.
    C. Shipman Jr., S.H. Smith, J.C. Drach, and D.L. Klayman, Antiviral activity of 2-acetylpyridine thiosemicarbazones against herpes simplex virus, Antimicrob. Agents Chemother. 19:682 (1981).PubMedGoogle Scholar
  17. 14.
    T. Spector, D.R. Averett, D.J. Nelson, C.U. Lambe, R.W. Morrison Jr., M.H. St. Clair, and P.A. Furman, Potentiation of antiherpetic activity of acyclovir by ribonucleotide reductase inhibition, Proc. Natl. Acad. Sci. USA 82:4254 (1985).PubMedCrossRefGoogle Scholar
  18. 15.
    C.J. Pfau, The thiosemicarbazones, Handb. Exp. Pharmacol. 61:147 (1982).CrossRefGoogle Scholar
  19. 16.
    J.A. Cooper, B. Moss, and E. Katz, Inhibition of vaccinia virus late protein synthesis by isatin-3-thiosemicarbazone: characterization and in vitro translation of viral mRNA, Virology 96:381 (1979).PubMedCrossRefGoogle Scholar
  20. 17.
    D.D. Perrin and A. Stünzi, Viral chemotherapy: antiviral actions of metal ions and metal-chelating agents, Pharmac. Ther. 12:255 (1981);CrossRefGoogle Scholar
  21. 17a.
    D.W. Hutchinson, Metal chelators as potential antiviral agents, Antiviral Res 5:193 (1985).PubMedCrossRefGoogle Scholar
  22. 18.
    J.S. Oxford and D.D. Perrin, Inhibition of the particle-associated RNA-dependent RNA polymerase activity of influenza viruses by chelating agents, J. Gen. Virol. 23:59 (1974).PubMedCrossRefGoogle Scholar
  23. 19.
    A.W. Galbraith, Influenza — recent developments in prophylaxis and treatment, Brit. Med. Bull. 41:381 (1985).PubMedGoogle Scholar
  24. 20.
    S.L. Barriere, Antiviral therapy, Pharm. Int. 139 (1984).Google Scholar
  25. 21.
    A.J. Hay, A.J. Wolstenholme, J.J. Skehel, and M.H. Smith, The molecular basis of the specific anti-influenza action of amantadine, EMBO J. 4:3021 (1985).PubMedGoogle Scholar
  26. 22.
    D.L. Swallow and G.L. Kampfner, The laboratory selection of antiviral agents, Brit. Med. Bull. 41:322 (1985).PubMedGoogle Scholar
  27. 23.
    K.R. Bharucha, K.C. Tin, I. Ajdukovic, and D. Ajdukovic, Antiviral l,2,3,4-tetrahydro-l,4-methanonaphthalene derivatives, US Patent 4,362,746 (1982).Google Scholar
  28. 24.
    P. Palese and J.L. Schulman, Inhibitor of viral neuraminidase as potential antiviral drugs in chemoprophylaxis and virus infections of the respiratory tract, Vol. 1, CRS Press, Cleveland, p. 189 (1977).Google Scholar
  29. 25.
    H.A. Blough, R. Kumarasamy, M. Massare, R.L. Giuntoli, S. Sprecher-Goldberger, and L. Thiry, Glycosylation inhibitors: mode of action and clinical efficacy, in “Herpes Viruses and Virus Chemotherapy”, R. Kono and A. Nakajima, eds., Elsevier Science Publ., Amsterdam, p. 211 (1985);Google Scholar
  30. 25a.
    see also JG. Mohanty and K.S. Rosenthal, 2-Deoxy-D-glucose inhibition of herpes simplex virus type-1 receptor expression, Antiviral Res. 6:137 (1986).PubMedCrossRefGoogle Scholar
  31. 26.
    O.P. Zhirnov, A.V. Ovcharenko, and A.G. Bukrinskaya, Suppression of influenza virus replication in infected mice by protease inhibitors, J. Gen. Virol. 65:191 (1984).PubMedCrossRefGoogle Scholar
  32. 27.
    J.J. McSharry, L.A. Caliguiri, and H.J. Eggers, Inhibition of uncoating of poliovirus by arildone, a new antiviral drug, Virology 97:307 (1979).PubMedCrossRefGoogle Scholar
  33. 28.
    G.D. Diana, M.A. McKinlay, C.J. Brisson, E.S. Zalay, J.V. Miralles, and U.J. Salvador, Isoxazoles with antipicornavirus activity, J. Med. Chem. 28:748 (1985).PubMedCrossRefGoogle Scholar
  34. 29.
    G.D. Diana and M.J. Otto, Inhibitors of Picornavirus uncoating as antiviral agents, Pharmac. Ther. 29:287 (1985).CrossRefGoogle Scholar
  35. 30.
    T.J. Smith, M.J. Kremer, M. Luo, G. Vriend, E. Arnold, G. Kamer, M.G. Rossmann, M.A. McKinlay, G.D. Diana, and M.J. Otto, The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating, Science 233, 1286 (1986).PubMedCrossRefGoogle Scholar
  36. 31.
    G.D. Diana, R.C. Oglesby, V. Akullian, P.M. Carabateas, D. Cutcliffe, J.P. Mallamo, M.J. Otto, M.A. McKinlay, E.G. Maliski, and S.J. Michalec, Structure-activity studies of 5-[[4-(4,5-dihydro-2-oxazolyl)phenoxy]alkyl]-3-methylisoxazoles: inhibitors of Picornavirus uncoating, J. Med. Chem. 30:838 (1987).CrossRefGoogle Scholar
  37. 32.
    R.J. Philipotts, R.W. Jones, D.C. Delong, S.E. Reed, J. Wallace, and D.A.J. Tyrrell, The activity of enviroxime against rhinovirus infection in man, Lancet i:1342 (1981).CrossRefGoogle Scholar
  38. 33.
    R.J. Phillpotts and D.A.J. Tyrrell, Rhinovirus colds, Brit. Med. Bull. 41:386 (1985).PubMedGoogle Scholar
  39. 34.
    I. Beladi, R. Pusztai, I. Mucsi, M. Bekay, and M. Gabor, Activity of some flavanoids against viruses, Ann. N.Y. Acad. Sci. 284:358 (1977);PubMedCrossRefGoogle Scholar
  40. 34a.
    A. Wacker and H.G. Eilmes, Antiviral activity of plant components, Part 1, Flavanoids, Arzneim. Forsch. 28:347 (1978).Google Scholar
  41. 35.
    R.J. Ash, R.A. Parker, A.C. Hagan, G.D. Mayer, RMI 15,731 (l-[5-tetradecyloxy-2-furanyl]-ethanone), a new antirhinovirus compound, Antimicrob. Agents Chemother. 16:301 (1979).PubMedGoogle Scholar
  42. 36.
    D.L. Swallow, R.A. Bucknall, W.E. Stanier, A. Hutchinson, and H. Gaskin, A New antirhinovirus compound, ICI 73602: structure-properties and spectrum of activity, Ann. N.Y. Acad. Sci. 284:305 (1977).PubMedCrossRefGoogle Scholar
  43. 37.
    L.D. Markley, Y.C. Tong, J.K. Dulworth, D.L. Steward, C.T. Goralski, H. Johnston, S.G. Wood, A.P. Vinogradoff, and T.M. Bargar, Antipicornavirus activity of substituted phenoxybenzenes and phenoxypyridines, J. Med. Chem. 29:427 (1986).PubMedCrossRefGoogle Scholar
  44. 38.
    A.S. Galabov, B.S. Galabov, and N.A. Neykova, Structure-activity relationships of diphenylthiourea antivirals, J. Med. Chem. 23:1048 (1980).PubMedCrossRefGoogle Scholar
  45. 39.
    G.M. Scott, R.J. Phillpotts, J. Wallace, D.S. Secher, K. Cantell, and D.A.J. Tyrrell, Purified interferon as protection against rhinovirus infection, Brit. Med. J. 284:1822 (1982);CrossRefGoogle Scholar
  46. 39a.
    G.M. Scott, R.J. Phillpotts, J. Wallace, C.L. Gauci, J. Greiner, and D.A.J. Tyrrell, Prevention of rhinovirus colds by human interferon alpha-2 from Escherichia coli, Lancet ii:186 (1982).CrossRefGoogle Scholar
  47. 40.
    R.J. Phillpotts, P.G. Higgins, J.S. Willman, D.A.J. Tyrrell, D.S. Freestone, and W.M. Shepherd, Intranasal lymphoblastoid interferon (“Wellferon”) prophylaxis against rhinovirus and influenza virus in volunteers, J. Interferon Res. 4:535 (1984).PubMedCrossRefGoogle Scholar
  48. 41.
    D.O. White, Antiviral chemotheapy, Med. J. Australia, 715 (1984).Google Scholar
  49. 42.
    P.W. Choppin, C.D. Richardson, and A. Scheid, Oligopeptides as specific antiviral agents, in: “Targets for the Design of Antiviral Agents”, E. De Clercq and R.T. Walker, eds., Plenum Press, New York and London, p. 287 (1984);Google Scholar
  50. 42a.
    C.D. Richardson and P.W. Choppin, Oligopeptides that specifically inhibit membrane fusion by paramyxoviruses: studies on the site of action, Virology 131:518 (1983);PubMedCrossRefGoogle Scholar
  51. 42b.
    see also P.W. Choppin, Basic virology, in: “Virology in Medicine”, H. Rothschild and J.C Cohen, eds., Oxford University Press, Oxford, p. 24 (1986).Google Scholar
  52. 43.
    W.H. Prusoff, T.-S. Lin, and M. Zucker, Potential targets for antiviral chemotherapy, Antiviral Res. 6:311 (1986).PubMedCrossRefGoogle Scholar
  53. 44.
    O.P. Zhirnov, A.V. Ovcharenko, and A.G. Bukrinskaya, Myxovirus replication in chicken embryos can be suppressed by aprotinin due to the blockage of viral glycoprotein cleavage, J. Gen. Virol. 66:1633 (1985);PubMedCrossRefGoogle Scholar
  54. 44a.
    see also O.P. Zhirnov, High protection of animals lethally infected with influenza virus by aprotinin-rimantadine combination, J. Med. Virol. 21:161 (1987).PubMedCrossRefGoogle Scholar
  55. 45.
    B.M. Dutia, M.C. Frame, J.H. Subak-Sharpe, W.N. Clark, and H.S. Marsden, Specific inhibition of herpesvirus ribonucleotide reductase by synthetic peptides, Nature 321:439 (1986).;PubMedCrossRefGoogle Scholar
  56. E.A. Cohen, P. Gaudreau, P. Brazeau, and Y. Langelier, Specific inhibition of herpesvirus ribonucleotide reductase by a nonapeptide derived from the carboxy terminus of subunit 2, Nature 321:441 (1986).PubMedCrossRefGoogle Scholar
  57. 46.
    C.B. Pert, J.M. Hill, M.R. Ruff, R.M. Berman, W.G. Robey, L.O. Arthur, F.W. Ruscetti, and W.L. Farrar, Octapeptides deduced from the neuropeptide receptor-like pattern of antigen T4 in brain potently inhibit human immunodeficiency virus receptor binding and T-cell infectivity, Proc. Natl. Acad. Sci. USA 83:9254 (1986).PubMedCrossRefGoogle Scholar
  58. 47.
    E. De Clercq, Chemotherapeutic approaches to the treatment of the acquired immune deficiency syndrome (AIDS), J. Med. Chem. 29:1561 (1986).PubMedCrossRefGoogle Scholar
  59. 48.
    M.E. Gore and P. Selby, Antiviral chemotherapy, Brit. J. Hosp. Med. 24: in press (1987).Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Stanley M. Roberts
    • 1
  1. 1.Department of ChemistryExeter UniversityExeter, DevonUK

Personalised recommendations