Oligopeptides as Specific Antiviral Agents

  • Purnell W. Choppin
  • Christopher D. Richardson
  • Andreas Scheid
Part of the NATO ASI Series book series (NSSA, volume 73)


The occurrence of this course is testimony to the recent progress toward the development of antiviral chemotherapy. Much of this progress has been due to the identification and characterization of viral enzymes, particularly those involved in nucleic acid synthesis, topics that are discussed extensively in this volume. In addition to the elucidation of the roles of viral enzymes, a great deal has also been learned about the biological activities of other viral proteins, and in some cases detailed information has been obtained on structure-function relationships of proteins with biological activities that are targets for inhibition. This presentation will deal with the development of specific oligopeptide inhibitors of paramyxoviruses and myxoviruses, inhibitors that were designed on the basis of information gained on the structure and biological functions of viral surface glycoproteins, including information that indicated that a specific region of the protein was involved in biological activity. The proteins are the fusion (F) protein of paramyxoviruses and the hemagglutinin (HA) protein of myxoviruses, and the step in virus replication that is inhibited is penetration of the virus into the cell, which occurs by fusion of the viral membrane with the cell membrane. These findings have been described in detail in several previous publications (Richardson et al., 1980, 1981, 1983; Choppin et al., 1981, 1983) and will be summarized briefly in this communication.


Influenza Virus Newcastle Disease Virus Cell Fusion Membrane Fusion Measle Virus 
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  1. Chanock, R. M., Parrott, R. H., Kapikian, A. Z., Kim, H. W., and Brandt, C. D., 1968, Possible role of immunological factors in. pathogenesis of RS lower respiratory tract disease, in: “Perspectives in Virology VI”, M. Pollard, ed., Academic Press, New York.Google Scholar
  2. Choppin, P. W., and Scheid, A., 1977, The biologic role of host-dependent proteolytic cleavage of a paramyxovirus glycoprotein, in: “Slow Virus Infectious of the Central Nervous System”, V. ter Meulen and M. Katz, eds., Springer Verlag, New York.Google Scholar
  3. Choppin, P. W., Richardson, C. D., Merz, D. C., and Scheid, A., 1981, Functions of surface glycoproteins of myxoviruses and paramyxoviruses and their inhibition, in: “Adhesion and Microorganism Pathogenicity”, Ciba Foundation Symposium, M. O’Connor, ed., Pitman Medical, London.Google Scholar
  4. Choppin, P. W., Richardson, C. D., and Scheid, A., 1983, Analogues of viral polypeptides which specifically inhibit viral replication, in: “Problems of Antiviral Therapy”, C. Stuart-Harris, ed., Academic Press, London and New York.Google Scholar
  5. Compans, R. W., Holmes, K. V., Dales, S., and Choppin, P. W., 1966, An electron microscopic study of moderate and virulent virus-cell interactions of the parainfluenza virus SV5, Virology 30: 411.PubMedCrossRefGoogle Scholar
  6. Crowell, R. L., 1980, Receptors as determinants of cellular tropism in picornavirus infections, in: “Receptors and Human Diseases”, A. G. Bearn and P. W. Choppin, eds., Josiah Macy, Jr. Foundation, New York.Google Scholar
  7. Enders, J. F., and Peebles, T. C., 1954, Propagation in tissue cultures of cytopathogenic agents from patients with measles virus, Proc. Soc. Exp. Biol. Med. 86: 277.PubMedGoogle Scholar
  8. Gething, M. J., White, J. M., and Waterfield, M. D., 1978, Purification of the fusion protein of Sendai virus: analysis of the NH2terminal sequence generated during precursor activation, Proc. Nat. Acad. Sci. U.S.A. 75: 2737.CrossRefGoogle Scholar
  9. Graves, M. C., Silver, S. M., and Choppin, P. W., 1978, Measles virus polypeptide synthesis in infected cells, Virology, 86: 254.PubMedCrossRefGoogle Scholar
  10. Helenius, A., Kartenbeck, J., Simono, K., and Fries, E., 1980, On the entry of Semliki Forest virus into BHK-21 cells, J. Cell Biol., 84: 404.PubMedCrossRefGoogle Scholar
  11. Henle, G.,Deinhardt, F., and Girardi, A., 1954, Cytolytic effects of mumps virus in tissue cultures of epithelial cells, Proc. Soc. Exp. Biol. Med., 87: 386.Google Scholar
  12. Holmes, K. V., and Choppin, P. W., 1966, On the role of the response of the cell membrane in determining virus virulence. Contrasting effects of the parainfluenza virus SV5 in two cell types, J. Exptl. Med. 124: 501.CrossRefGoogle Scholar
  13. Homma, M., and Ohuchi, M., 1973, Trypsin action on the growth of Sendai virus in tissue culture cells. III. Structural difference of Sendai viruses grown in eggs and in tissue culture cells, J. Virol. 12: 1457.PubMedGoogle Scholar
  14. Hsu, M.-C., Scheid, A., and Choppin, P. W., 1979, Reconstitution of membranes with individual paramyxovirus glycoproteins and phospholipid in cholate solution, Virology, 95: 476.PubMedCrossRefGoogle Scholar
  15. Hsu, M.-C., Scheid, A., and Choppin, P. W., 1981, Activation of the Sendai virus fusion protein (F) involves a conformational change with exposure of a new hydrophobic region, J. Biol. Chem. 256: 3357.Google Scholar
  16. Hsu, M.-C., Scheid, A., and Choppin, P. W., 1982, Enhancement of membrane fusing activity of Sendai virus by exposure of the virus to basic pH is correlated with a conformational change in the fusion protein, Proc. Natl. Acad. Sci. U.S.A., 79: 5862.PubMedCrossRefGoogle Scholar
  17. Huang, R. T. C., Rott, R., and Klenk, H.-D., 1981, Influenza viruses cause hemolysis and fusion of cells. Virology, 110: 243.PubMedCrossRefGoogle Scholar
  18. Klenk, H.-D., Rott, R., Orlich, M., and Bltidorn, J., 1975, Activation of influenza A viruses by trypsin treatment, Virology, 68: 425.CrossRefGoogle Scholar
  19. Laver, G., and Air, G., eds., 1980, “Structure and Variation in Influenza Virus”, Elsevier/North Holland, New York.Google Scholar
  20. Lazarowitz, S. G., and Choppin, P. W., 1975, Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin polypeptide, Virology, 68: 440.PubMedCrossRefGoogle Scholar
  21. Lazarowitz, S. G., Compans, R. W., and Choppin, P. W., 1971, Influenza virus structural and non-structural proteins in infected cells and their plasma membranes, Virology, 46: 830.PubMedCrossRefGoogle Scholar
  22. Lazarowitz, S. G., Goldberg, A. R., and Choppin, P. W., 1973, Proteolytic cleavage by plasmin of the HA polypeptide of influenza virus: Host cell activation of serum plasminogen, Virology, 56: 172.PubMedCrossRefGoogle Scholar
  23. Lenard, J., and Miller, D. K., 1981, pH-dependent hemolysis by influenza, Semliki Forest virus, and Sendai virus, Virology, 110: 479.Google Scholar
  24. Lomniczi, B., Meager, A., and Burke, D. C., 1971, Virus RNA and protein synthesis in cells infected with different strains of Newcastle disease virus, J. Gen. Virol., 13: 111.PubMedCrossRefGoogle Scholar
  25. Maeda, T., Kawasaki, K., and Ohnishi, S.-I., 1981, Interaction of influenza virus hemagglutinin with target membrane lipids is a key step in virus-induced hemolysis and fusion at pH 5.2, Proc. Nat. Acad. Sci. U.S.A., 78: 4133.CrossRefGoogle Scholar
  26. Merz, D. C., Scheid, A., and Choppin, P. W., 1980, The importance of antibodies to the fusion glycoprotein (F) of paramyxoviruses in the prevention of spread of infection, J. Exptl. Med. 151: 275.CrossRefGoogle Scholar
  27. Miller, F. A., Dixon, G. J., Arnett, G., Dice, J. R., Rightsel, W. A., Schabel, F. M., and McLean, J. W., 1968, Antiviral activity of carbobenzoxy di-and tripeptides on measles virus, Appl. Microbiol. 16: 1489.PubMedGoogle Scholar
  28. Nagai, Y., Klenk, H.-D., and Rott, R., 1976, Proteolytic cleavage of viral glycoproteins and its significance for the virulence of Newcastle disease virus, Virology, 72: 494.PubMedCrossRefGoogle Scholar
  29. Nagai, Y., and Klenk, H.-D., 1977, Activation of precursors to both glycoproteins of Newcastle disease virus by proteolytic cleavage, Virology, 77: 125.PubMedCrossRefGoogle Scholar
  30. Norrby, E., 1971, The effect of carbobenzoxy tripeptides on the biological activity of measles virus, Virology, 44: 599.PubMedCrossRefGoogle Scholar
  31. Norrby, E., and Gollmar, Y., 1975, Identification of measles virus-specific hemolysis-inhibiting antibodies separate from hemagglutination-inhibiting antibodies, Infect. Immun. 11: 231.PubMedGoogle Scholar
  32. Norrby, E., and Penttinen, K., 1978, Differences in antibodies to the surface components of mumps virus after immunization with formalin-inactivated and live virus vaccines, J. Infect. Dis. 138: 672.PubMedCrossRefGoogle Scholar
  33. Norrby, E., Enders-Ruckle, G., and ter Meulen, V., 1975, Differences in the appearance of antibodies to structural components of measles virus after immunization with inactivated and live virus, J. Infect. Dis. 132: 262.PubMedCrossRefGoogle Scholar
  34. Prehm, P., Scheid, A., and Choppin, P. W., 1979, The carbohydrate structure of the glycoproteins of the paramyxovirus SV5 grown in bovine kidney (MDBK) cells, J. Biol. Chem., 254: 9669.PubMedGoogle Scholar
  35. Richardson, C. D., Scheid, A., and Choppin, P. W., 1980, Specific inhibition of paramyxovirus and myxovirus replication by oligopeptides with amino acid sequences similar to those at the N-termini of the F1 or HA2 viral polypeptides, Virology, 105: 205.PubMedCrossRefGoogle Scholar
  36. Richardson, C. D., Scheid, A., and Choppin, P. W., 1981, Specific inhibition of paramyxovirus and myxovirus replication by hydrophobic oligopeptides, in: “The Replication of Negative Strand Viruses”, D. H. L. Bishop and R. W. Compans, eds., Elsevier-North Holland, New York.Google Scholar
  37. Richardson, C. D., Scheid, A., and Choppin, P. W., 1983, Studies on the site of action of oligopeptides that specifically inhibit the membrane fusion activity of paramyxoviruses, Virology, to be submitted.Google Scholar
  38. Scheid, A., and Choppin, P. W., 1973, Isolation and purification of the envelope proteins of Newcastle disease virus, J. Virol. 11: 263.PubMedGoogle Scholar
  39. Scheid, A., and Choppin, P. W., 1974a, Identification of biological activities of paramyxovirus glycoproteins. Activation of cell fusion, hemolysis and infectivity by proteolytic cleavage of an inactive precursor protein of Sendai virus, Virology, 57: 475.PubMedCrossRefGoogle Scholar
  40. Scheid, A., and Choppin, P. W., 1974, The hemagglutinating and neuraminidase protein of a paramyxovirus: Interaction with neuraminic acid in affinity chromatography. Virology, 62: 125.PubMedCrossRefGoogle Scholar
  41. Scheid, A., and Choppin, P. W., 1975, Isolation of paramyxovirus glycoproteins and identification of their biological properties, in: “Negative Strand Viruses”, B.W.J. Mahy and R.D. Barry, eds., Academic Press, London.Google Scholar
  42. Scheid, A., and Choppin, P. W., 1976, Protease activation mutants of Sendai virus: Activation of biological properties by specific proteases, Virology, 69: 265.PubMedCrossRefGoogle Scholar
  43. Scheid, A., and Choppin, P. W., 1977, Two disulfide-linked polypeptide chains constitute the active F protein of paramyxoviruses, Virology, 80: 54.PubMedCrossRefGoogle Scholar
  44. Scheid, A., Caliguiri, L. A., Compans, R. W., and Choppin, P. W., 1972, Isolation of paramyxovirus glycoproteins. Association of both hemagglutinating and neuraminidase activities with the larger SV5 glycoprotein. Virology, 50: 640.PubMedCrossRefGoogle Scholar
  45. Scheid, A., Graves, M. C., Silver, S. M., and Choppin, P. W., 1978, Studies on the structure and function of paramyxovirus glycoproteins, in: “Negative Strand Viruses and the Host Cell”, B.W.J. Mahy and R.D. Barry, eds., Academic Press, London.Google Scholar
  46. Skehel, J. J., and Waterfield, M. D., 1975, Studies of the primary structure of the influenza virus hemagglutinin, Proc. Nat. Acad. Sci. U.S.A. 72: 93.CrossRefGoogle Scholar
  47. Skehel, J. J., Bayley, P. M., Brown, E. B., Martin, S. R., Waterfield, M. D., White, J. M., Wilson, I. A., and Wiley, D. C., 1982, Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion, Proc. Natl. Acad. Sci. U.S.A., 79:968.Google Scholar
  48. Tozawa, H., Watanabe, M., and Ishida, N., 1973, Structural components of Sendai virus. Serological, and physicochemical characterization of hemagglutinin subunit associated with neuraminidase activity, Virology, 55: 242.PubMedCrossRefGoogle Scholar
  49. White, J., Matlin, K., and Helenius, A., 1981, Cell fusion by Semliki Forest influenza, and vesicular stomatitis, viruses, J. Cell Biol., 89: 674.PubMedCrossRefGoogle Scholar
  50. White, J., Helenius, A., and Gething, M. J., 1982, Haemagglutinin of influenza virus expressed from a cloned gene promotes membrane fusion, Nature, 300: 658.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Purnell W. Choppin
    • 1
  • Christopher D. Richardson
    • 1
  • Andreas Scheid
    • 1
  1. 1.The Rockefeller UniversityNew YorkUSA

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