Perspectives in the Use of Antiviral Agents for Prevention and Treatment of Respiratory Virus Infections

  • S. J. Sperber
  • F. G. Hayden
Part of the Developments in Medical Virology book series (DIMV, volume 3)


Respiratory viral infections are the most common infectious diseases of man and a major cause of morbidity and mortality globally. In developing countries respiratory viruses remain an important cause of childhood mortality (1). Acute respiratory diseases, which are frequently caused by viral infections, account for 20% of childhood mortality and in some parts of the world are the commonest cause of death in children (1). It is estimated that 2.2 million deaths occur throughout the world annually as a result of acute respiratory diseases. These diseases account for about 13% of all deaths in Africa, Central America and the developing countries of Asia, compared to 3% in North America (1). In developed countries certain viral infections continue to cause significant mortality in high-risk groups, particularly infants and the elderly. In the United States, influenza virus epidemics have been estimated to have been associated with over 10,000 excess deaths during 18 of the past 28 years (2).


Respiratory Syncytial Virus Antiviral Agent Common Cold Respiratory Virus Respiratory Viral Infection 
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.


  1. 1.
    WHO Scientific Group on Viral Respiratory Diseases. WHO Technical Report Series 642: 7–49, 1980.Google Scholar
  2. 2.
    Centers for Disease Control. Morbidity and Mortality Weekly Report 35:317–331, 1986.Google Scholar
  3. 3.
    National Center for Health Statistics. Vital and Health Statistics, Series 10 141: 11–18, 1982.Google Scholar
  4. 4.
    Couch, R.B. J. Infect. Dis. 150:167–173, 1984.PubMedCrossRefGoogle Scholar
  5. 5.
    Gwaltney, J.M. Jr., Hendley, J.O., Simon, G. and Jordan. W.S. N. Engl. J. Med. 275:1261–1268, 1966.PubMedCrossRefGoogle Scholar
  6. 6.
    Dingle, J.H., Badger, G.F. and Jordan, W.S. Jr. Illness in the Home. Press of Western Reserve University, Cleveland, 1964, pp. 19–96.Google Scholar
  7. 7.
    Gwaltney, J.M., Jr. Viral Infections of Humans (Ed. A.S. Evans), Plenum Press, New York, 1982, pp.491–517.Google Scholar
  8. 8.
    Douglas, R.G., Jr. N. Engl. J. Med. 314:114–115, 1986.PubMedCrossRefGoogle Scholar
  9. 9.
    Choppin, P.W. In: Virology in Medicine (Eds. H. Rothschild and J.C. Cohen) Oxford University Press, New York, 1986, pp. 3–45.Google Scholar
  10. 10.
    Barker, W.H. In: Options for the Control of Influenza (Eds. A.P. Kendal and P.A. Patriarcal), Alan R. Liss, Inc., New York, 1986, pp. 75–87.Google Scholar
  11. 11.
    Horn, M.E., Reed, S.E. and Taylor, P. Arch. Dis. Child. 54:587–592, 1979.PubMedCrossRefGoogle Scholar
  12. 12.
    Isaacs, D., Flowers D., Clarke, J.R., Valman, H.B. and Macnaughton, M.R. Arch. Dis. Child. 58:500–503, 1983.PubMedCrossRefGoogle Scholar
  13. 13.
    Carlsen, K.H., Orstavik, I., Leegaard, J. and Hoeg, H. Arch. Dis. Child. 59:310–315, 1984.PubMedCrossRefGoogle Scholar
  14. 14.
    Monto, A.S. and Ross, J.W. Am. J. Epidemiol. 107:57–64, 1978.PubMedGoogle Scholar
  15. 15.
    Hall, C.B., Powell, K.R., MacDonald, N.E., Gala, C.L., Menegus, M.E., Suffin, S.C. and Cohen, H.J. N. Engl. J. Med. 315:77–81, 1986.PubMedCrossRefGoogle Scholar
  16. 16.
    Herrman, E.C., Jr. and Herrman, J.A. In: Viral Chemotherapy (Ed. D. Shugar), Permagon Press, New York, 1984, pp.53–54.Google Scholar
  17. 17.
    Masters, H., Lauer, B., Webber, K., Groothuis, J. and Wren, C. In: Program and Abstracts of the Twenty-sixth Interscience Conference on Antimicrobial Agents and Chemotherapy. Am. Soc. Microbiol. 1986, abst. #82, p. 111.Google Scholar
  18. 18.
    Menegus, M.A. and Douglas, R.G., Jr. In: Principles and Practices of Infectious Diseases, 2nd Edition, (Eds. G.L. Mandell, R.G. Douglas, Jr., and J.E. Bennett), John Wiley and Sons, New York, 1985, pp. 138–149.Google Scholar
  19. 19.
    Couch, R.B., Kasel, J.A., Glezen, W.P., Cate, T.R., Six, H.R., Taber, L.H., Frank, A.L., Greenberg, S.B., Zahradnik, J.M. and Keitel, W.A. J. Infect. Dis. 153:431–440, 1986.PubMedCrossRefGoogle Scholar
  20. 20.
    Johnson, P.R., Feldman, S., Thompson, J.M., Mahoney, J.D. and Wright, P.F. J. Infect. Dis. 154:121–127, 1986.PubMedCrossRefGoogle Scholar
  21. 21.
    Top, F.H., Jr. Yale J. Biology and Med. 48:185–195, 1975.Google Scholar
  22. 22.
    Kapikian, A.Z., Mitchell, R.H., Chanock, R.M., Shvedoff, R.A. and Stewart, C.E., Am. J. Epidemiol. 89:405–421, 1969.PubMedGoogle Scholar
  23. 23.
    McIntosh, K., Arbeter, A.M., Stahl, M.K., Orr, J.A., Hodes, D. S. and Ellis, E.F. Pediatr. Res. 8:689–696, 1974.PubMedGoogle Scholar
  24. 24.
    Mims, C.A. The Pathogenesis of Infectious Diseases, Academic Press, New York, 1977, p. 129.Google Scholar
  25. 25.
    Hayden, G.F., Hendley, J.O. and Gwaltney, J.M., Jr. J. Infect. Dis. 152:403–407, 1985.PubMedCrossRefGoogle Scholar
  26. 26.
    Murphy, D., Todd, J.K., Chao, R.K., Orr, I. and Mcintosh, K. J. Pediatrics 99:746–750, 1981.CrossRefGoogle Scholar
  27. 27.
    Hall, C.B. and Douglas, R.G., Jr. Am. J. Dis. Child. 135:512–515, 1981.PubMedGoogle Scholar
  28. 28.
    Gala, C.L., Hall, C.B., Schnabel, K.C., Pincus, P.H., Blossom, P., Hildreth, S.W., Betts, R.F. and Douglas, R.G., Jr. JAMA 256:2706–2708, 1986.PubMedCrossRefGoogle Scholar
  29. 29.
    Hayden, G.F., Gwaltney, J.M., Jr., Thacker, D.F. and Hendley, J.O. Antiviral Res. 5:103–109, 1985.PubMedCrossRefGoogle Scholar
  30. 30.
    Dick, E.C., Hossain, S.U., Mink, K.A., Meschievitz, CK., Schultz, S.B., Raynor, W.J. and Inhorn, S.L. J. Infect. Dis. 153:352–356, 1986.PubMedCrossRefGoogle Scholar
  31. 31.
    Gwaltney, J.M., Jr. and Hendley, J.O. Am. J. Epidemiol. 116:828–833, 1982.PubMedGoogle Scholar
  32. 32.
    Gwaltney, J.M., Jr., Moskalski, P.B. and Hendley, J.O. J. Infect. Dis. 142:811–815, 1980.PubMedCrossRefGoogle Scholar
  33. 33.
    Andrewes, C., The Common Cold. W.W. Norton, New York, 1965, pp. 156–157.Google Scholar
  34. 34.
    Hemming, V.G., Prince, G.A., Horswood, R.L., London, W.T., Murphy, B.R., Walsh, E.E., Fischer, G.W., Weisman, L.E., Baron, P.A. and Chanock, R.M. J. Infect. Dis. 152:1083–1087, 1985.PubMedCrossRefGoogle Scholar
  35. 35.
    Douglas, R.M., Albrecht, J.K., Miles, H.B., Moore, B.W., Read, R., Worswick, D.A. and Woodward, A.J. J. Infect. Dis. 151:731–736, 1985.PubMedCrossRefGoogle Scholar
  36. 36.
    Monto, A.S., Shope, T.C., Schwartz, S.A. and Albrecht, J.K. J. Infect. Dis. 154:128–133, 1986.PubMedCrossRefGoogle Scholar
  37. 37.
    Hayden, F.G., Gwaltney, J.M., Jr. and Johns, M.E. Antiviral Res. 5:111–116, 1985.PubMedCrossRefGoogle Scholar
  38. 38.
    Solov’ev, V.D. Bull WHO 41:683–688, 1969.PubMedGoogle Scholar
  39. 39.
    Merigan, T.C., Hall, T.S., Reed, S.E. and Tyrrell, D.A.J. Lancet 1:563–567, 1973.PubMedCrossRefGoogle Scholar
  40. 40.
    Hayden, F.G. In: Antiviral Chemotherapy, New Directions for Clinical Application and Research (Eds. J. Mills and L. Corey), Elsevier, New York, 1986, pp. 28–39.Google Scholar
  41. 41.
    Samo, T.C., Greenberg, S.B., Palmer, J.M., Couch, R.B., Harmon, M.W. and Johnson, P.E. J. Infect. Dis. 150:2,181–188, 1984.PubMedCrossRefGoogle Scholar
  42. 42.
    Dolin, R., Reichman, R.C., Madore, H.P., Maynard, R., Linton, P.N. and Webber-Jones, J. N. Engl. J. Med. 307:580–584, 1982.PubMedCrossRefGoogle Scholar
  43. 43.
    Schulman, J.L. Proc. Soc. Exp. Biol. Med. 128:1173–1178, 1968.Google Scholar
  44. 44.
    Crutcher, J.E. and Kantner, T.R. J. Clin. Pharmacol. 21:9–15, 1981.PubMedCrossRefGoogle Scholar
  45. 45.
    Naclerio, R.M., Gwaltney, J.M., Jr., Hendley, J.O., Eggleston, P., Baumgarten, C.R., Lichtenstein, L.M. and Proud, D. Clin. Res. 33: 613A, 1985.Google Scholar
  46. 46.
    Howard, J.C., Jr., Kantner, T.R., Lilienfield, Princiotto, J.V., Krum, R.E., Cruther, J.E., Belman, M.A. and Danzig, M.R. JAMA 242:2414–2417, 1979.PubMedCrossRefGoogle Scholar
  47. 47.
    Millet, V.M., Dreisbach, M. and Bryson, Y.J. Antimicrob. Agents Chemother. 21:1–4, 1982.PubMedGoogle Scholar
  48. 48.
    Stanley, E.D., Jackson, G.G., Panusam, C., Rubenis, M. and Dirda, V. JAMA 231:1248–1251, 1975.PubMedCrossRefGoogle Scholar
  49. 49.
    Waldman, R.J., Hall, W.N., McGee, H. and Van Amburg, G. JAMA 247:3089–3094, 1982.PubMedCrossRefGoogle Scholar
  50. 50.
    Saketkhoo, K., Januszkiewicz, A. and Sackner, M.A. Chest 74:408–410, 1978.PubMedCrossRefGoogle Scholar
  51. 51.
    Ishitsuka, H., Ohsawa, C., Ohiwa, T., Umeda, I. and Suhara Y. Antimicrob. Agents Chemother. 22:611–616, 1982.PubMedGoogle Scholar
  52. 52.
    Wingfield, W.L., Pollack, D. and Grunert, R.R. N. Engl. J. Med. 281:579–581, 1969.PubMedCrossRefGoogle Scholar
  53. 53.
    Van Voris, L.P., Betts, R.F., Hayden, F.G., Christmas, W.A. and Douglas, R.G., Jr. JAMA 245:1128–1131, 1981.PubMedCrossRefGoogle Scholar
  54. 54.
    Hall, C.B., McBride, J.T., Gala, C.L., Dolin, R. and Markovitz, D. In: Options for the Control of Influenza, (Eds. A. P. Kendal and P. A. Patriarca), Alan R. Liss, Inc., New York, 1986, pp. 331–341.Google Scholar
  55. 55.
    Fishaut, M., Tubergen, D. and Mcintosh, K. J. Pediatr. 96:179–186, 1980.PubMedCrossRefGoogle Scholar
  56. 56.
    Heider, H., Adamczyk, B., Presber, H.W., Schroeder, C., Feldblum R. and Indulen, M.K. Acta Virol. 25: 395–401, 1981.PubMedGoogle Scholar
  57. 57.
    Webster, R.G., Kawaokay, Bean, W.J., Beard, C.W. and Brugh, M. J. Virol. 55:173–176, 1985.PubMedGoogle Scholar
  58. 58.
    Smith, C.B., Charette, R.P., Fox, J.P., Cooney, M.K. and Hall, C.E. J. Infect.Google Scholar
  59. Dis. 141:548–554, 1980.Google Scholar
  60. 59.
    Harmon, M.W., Greenberg, S.B. and Couch, R.B. Proc. Soc. Exp. Bio. Med. 152:598–602, 1976.Google Scholar
  61. 60.
    Greenberg, S., Harmon, M.W., Johnson, P.E. and Couch, R.B. Antimicrob. Agent. Chemoth. 14:596–600, 1978.Google Scholar
  62. 61.
    Hardy, J.G., Lee, S.W. and Wilson, C.G. J. Pharm. Pharmacol. 37:294–297, 1985.PubMedCrossRefGoogle Scholar
  63. 62.
    Aoki, F.Y. and Crawley, J.C.W. Br. J. Clin. Pharmac. 3:869–878, 1976.Google Scholar
  64. 63.
    Hayden, F.G. and Gwaltney, J.M., Jr. J. Infect. Dis. 150:174–180, 1984.PubMedCrossRefGoogle Scholar
  65. 64.
    Hayden, F.G., Mills, S.E. and Johns, M.E. J. Infect. Dis. 148:914–921, 1983.PubMedCrossRefGoogle Scholar
  66. 65.
    Hayden, F.G., Zylidnikov, D.M., Iljenko, V.I. and Padolka, Y.V. Antiviral Res. 2:147–153, 1982.PubMedCrossRefGoogle Scholar
  67. 66.
    Hayden, F.G., Hall, W.J. and Douglas R.G., Jr. J. Infect. Dis. 141:535–542, 1980.PubMedCrossRefGoogle Scholar
  68. 67.
    Knight, V., Bloom, K., Wilson S.Z. and Wilson, R.K. Antimicrob. Agents Chemother. 16:572–578, 1979.PubMedGoogle Scholar
  69. 68.
    Muldoon, R.L., Stanley, E.D. and Jackson, G.G. Am. Rev. Resp. Dis. 113:487–491, 1976.PubMedGoogle Scholar
  70. 69.
    Clover, R., Ramsey C. Jr., Crawford S. and Abell, T. J. Cellular Biochemistry 9C Supplement: 286, 1985.Google Scholar
  71. 70.
    Mcintosh, K. - personal communication.Google Scholar
  72. 71.
    Sundmacher, R., Mattes, A., Neumann-Haefelin, D., Papendick, U. and Springmeoer, U. J. Interferon Res. 6: 30–38, 1986.Google Scholar
  73. 72.
    Gwaltney, J.M., Jr. In: Viral Infections in Oral Medicine (Eds. J. Hooks and G. Jordan), Eslevier, New York, 1982, pp. 243–253.Google Scholar
  74. 73.
    Douglas, R.M., Moore, B.W., Miles, H.B., Davies, L.M., Graham, N.M.H., Ryan, P., Worswick, O.A. and Albrecht, J.K. N. Engl. J. Med. 314:66–70, 1986.Google Scholar
  75. 74.
    Hayden, F.G., Albrecht, J.K., Daiser, D.L. and Gwaltney, J.M. N. Engl. J. Med. 314:71–75, 1986.PubMedCrossRefGoogle Scholar
  76. 75.
    Galbraith, A.W., Oxford, J.S., Schild, G.C. and Watson, G.I. Lancet 2:1026–1028, 1969.PubMedCrossRefGoogle Scholar
  77. 76.
    Galbraith, A.W., Oxford, J.S., Schild, G.C. and Watson, G.I. Bull WHO 41: 677–682, 1969.PubMedGoogle Scholar
  78. 77.
    O’Donoghue, J.M., Ray, C.G., Terry, D.W., Jr. and Beaty, H.N. Am. J. Epidemiol. 97:276–282, 1973.PubMedGoogle Scholar
  79. 78.
    Atkinson, W.L., Arden, N.H., Patriarca, P.A., Leslie, N., Lui, K-J. and Gohd, R. Arch. Intern. Med. 246:1751–1756, 1986.CrossRefGoogle Scholar
  80. 79.
    Payler, D.K. and Purdham, P.A. Lancet 1:502–504, 1984.PubMedCrossRefGoogle Scholar
  81. 80.
    Little, J.W., Hall, W.J., Douglas, R.G., Jr., Mudholkar, G.S., Speers, D.M. and Patel, K. Am. Rev. Resp. Dis. 118:295–303, 1978.PubMedGoogle Scholar
  82. 81.
    Couch, R.B. and Jackson, G.G. J. Infect. Dis. 134:516–527, 1976.PubMedCrossRefGoogle Scholar
  83. 82.
    Hall, C.B., McBride, J.T., Walsh, E.E., Bell, D.M., Gala, C.L., Hildreth, S., Eyck, L.G.T. and Hall, W.J. N. Engl. J. Med. 308:1443–1447, 1983.Google Scholar
  84. 83.
    Just, M., Berger, R., Ruuskanen, O., Ludin, M. and Linder, S. J. Interferon Res. 6:32, 1968.Google Scholar
  85. 84.
    Hayden, F.G. and Gwaltney, J.M., Jr. Antimicrob. Agents Chemother. 21:892–897, 1982.PubMedGoogle Scholar
  86. 85.
    Abraham, G. and Colonno, R.J. J. Virol. 51:340–345, 1984.PubMedGoogle Scholar
  87. 86.
    Colonno, R.J., Callahan, P.L. and Long, W.J. J. Virol. 57:7–12, 1986.PubMedGoogle Scholar
  88. 87.
    Hayden, F.G., Colonno, R.J. and Gwaltney, J.M., Jr. - unpublished observations.Google Scholar
  89. 88.
    Ninomiya, Y., Ohsawa, D., Aoyama, M., Umeda, I., Suhara, Y. and Ishitsuka, H. Virology 134:269–276, 1984.PubMedCrossRefGoogle Scholar
  90. 89.
    Smith, T.J., Kremer, M.J., Luo, M., Vriend, G., Arnold, E., Kamer, G., Rossmann, G., McKinlay, M.A., Diana, G.D. and Otto, M.J. Science 233:1286–1293, 1986.PubMedCrossRefGoogle Scholar
  91. 90.
    Couch, R.B. and Six, H.R. In: Antiviral Chemotherapy, New Directions for Clinical Application and Research (Eds. J. Mills and L. Corey), Elsevier, New York, 1986, pp. 50–57.Google Scholar
  92. 91.
    Galasso, G.J. J. Antimicrob. Chemother. 14 Suppl A:127–136, 1984.PubMedGoogle Scholar
  93. 92.
    Richardson, C.D. and Choppin, P.W. Virology 131:518–532, 1983.PubMedCrossRefGoogle Scholar
  94. 93.
    Oxford, J.S. Br. Med. Bulletin 41:396–400, 1985.Google Scholar
  95. 94.
    Prusoff, W.H., Lin, T-S. and Zucker, M. Antiviral Res. 6:311–328, 1986.PubMedCrossRefGoogle Scholar
  96. 95.
    Ahmad, A.L.M. and Tyrrell, D.A.J. Antiviral Res. 6:241–252, 1986.PubMedCrossRefGoogle Scholar
  97. 96.
    Hayden, F.G., Schlepushkin, A.N. and Pushkarskaya, N.L. Antimicrob. Agents Chemother. 25:53–57, 1984.PubMedGoogle Scholar
  98. 97.
    Galegov, G.A., Pushkarskaya, N.L., Obrosova-Serova, N.P. and Zhdanov, V.M. Experimentia 33:905–906, 1977.CrossRefGoogle Scholar
  99. 98.
    Wilson, S.Z., Knight, V., Wyde, P.R., Drake, S. and Couch, R.B. Antimicrob. Agents Chemother. 17:642–648, 1980.PubMedGoogle Scholar
  100. 99.
    Hayden, F.G., Cote, K.M. and Douglas, R.G., Jr. Antimicrob. Agents Chemother. 17:865–870, 1980.PubMedGoogle Scholar
  101. 100.
    Came, P.E., Schafer, T.W. and Silver, G.H. J. Infect. Dis. 133 Supplement: A136–139, 1976.PubMedCrossRefGoogle Scholar
  102. 101.
    Grunert, R.R. Ann. Rev. Microbiol. 33:335–353, 1979.CrossRefGoogle Scholar
  103. 102.
    Bleidner, W.E., Harmon, J.B., Hewes, W.E., Lynes, T.E. and Hermann, E.C. J. Pharmacol. Exp. Ther. 150:484–490, 1965.PubMedGoogle Scholar
  104. 103.
    Hayden, F.G., Hoffman, H.E. and Spyker, D.A. Antimicrob. Agents Chemother. 23:458–464, 1983.PubMedGoogle Scholar
  105. 104.
    Karlowski, T.R., Chalmers, T.C., Frenkel, L.D., Kapikian, A.Z., Lewis, T.L. and Lynch, J.M. JAMA 231:1038–1042, 1975.PubMedCrossRefGoogle Scholar
  106. 105.
    Chalmers, T.C. Amer. J. Med. 58:532–536, 1975.PubMedCrossRefGoogle Scholar
  107. 106.
    Coulehna, J.L., Eberhard, S., Kapner, L., Taylor, F., Rogers, K. and Garry, P. N. Engl. J. Med. 295:973–977, 1976.CrossRefGoogle Scholar
  108. 107.
    Pitt, H.A. and Costrini, A.M. JAMA 241:908–911, 1979.PubMedCrossRefGoogle Scholar
  109. 108.
    Carr, A.B., Einstein, R., Lai, L.Y.C., Martin, N.G. and Starmer, G.A. Med. J. Aust. 2:411–412, 1981.PubMedGoogle Scholar
  110. 109.
    Eby, G.A., Davis, D.R. and Halcomb, W.H. Antimicrob. Agents Chemother. 25:20–24, 1984.PubMedGoogle Scholar
  111. 110.
    Farr, B.M. and Gwaltney, J.M., Jr. J. Chronic Diseases, in press.Google Scholar
  112. 111.
    Richman, D.D., Yazaki, P. and Hostetier, K.Y. Virology 112:81–90, 1981.PubMedCrossRefGoogle Scholar
  113. 112.
    Powell, K.R., Shorr, R., Cherry, J.D. and Hendley, J.O. J. Infect. Dis. 136:109–111, 1977.CrossRefGoogle Scholar
  114. 113.
    Hayden, F.G., Minocha, A., Spyker, D.A. and Hoffman, H.E. Antimicrob. Agents Chemother. 28:216–221, 1985.PubMedGoogle Scholar
  115. 114.
    Knight, V., Wilson, S.Z., Quarles, J.M., Greggs, S.E., McClung, H.W., Waters, B.K., Cameron, R.W., Zerwas, J.M. and Couch, R.B. Lancet 2:945–949, 1981.PubMedCrossRefGoogle Scholar
  116. 115.
    Hayden, F.G. and Gwaltney, J.M., Jr. Antiviral Res. 3:67–71, 1983.PubMedCrossRefGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing 1988

Authors and Affiliations

  • S. J. Sperber
    • 1
  • F. G. Hayden
    • 1
  1. 1.Departments of Internal Medicine and PathologyUniversity of Virginia School of MedicineCharlottesvilleUSA

Personalised recommendations