Skip to main content
Log in

Future prospects in antiviral therapy

  • Published:
Pharmaceutisch Weekblad Aims and scope Submit manuscript

Abstract

Two important stumbling blocks to the development of effective and nontoxic antiviral drugs are the intracellular localization of the virus and the fact that a virus uses host cell functions to multiply. Therefore, new antiviral drugs must act on a virus-specific function. Most currently available useful antiviral drugs are the result of compound screening of large numbers of possible agents. Advances in our understanding of the molecular biology and biochemistry of the viral multiplication cycle and new laboratory techniques for determining the molecular sites of action have now made it possible to develop and screen new antiviral drugs in a more purposeful manner. Another possible option in antiviral therapy is combination therapy using drugs that enhance the therapeutic effect or diminish side-effects. The most promising new antiviral drugs are discussed according to the different steps they affect in the viral multiplication process. Combination therapy is also reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Wiltink EHH, Janknegt R. Antiviral drugs. Pharm Weekbl [Sci] 1991;13:58–69.

    Google Scholar 

  2. Sim IS. Virus replication: target functions and events for virus-specific inhibiters. In: Galasso GJ, Whitley RJ, Merigan TC, eds. Antiviral agents and viral diseases of man. 3rd ed. New York: Raven Press, 1990:1–47.

    Google Scholar 

  3. Sandström E. Antiviral therapy in human immunodeficiency virus infection. Drugs 1989;38:417–50.

    PubMed  Google Scholar 

  4. Yarchoan R, Mitsuya H, Broder S. Clinical and basic advances in the anti-retroviral therapy of human immunodeficiency virus infection. Am J Med 1989;87:191–200.

    PubMed  Google Scholar 

  5. Capon DJ, Chamow SM, Mordenti J, Marsters SA, Gregory T, Mitsuya H, et al. Designing CD4 immunoadhesins for AIDS therapy. Nature 1989;337:525–531.

    PubMed  Google Scholar 

  6. Moore JP, Weiss RA, Passive primate protection. Nature 1991;352:371–7.

    Google Scholar 

  7. Daar ES, Li XL, Moudgil T, Ho DD. High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates. Proc Natl Acad Sci USA 1990;87:6574–78.

    PubMed  Google Scholar 

  8. Abrams DI, Kuno S, Wong R, Jeffords K, Nash M, Molaghan JB, et al. Oral dextran sulfate (UA 001) in the treatment of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Ann Intern Med 1989;110:183–8.

    PubMed  Google Scholar 

  9. Lüscher-Mattli M, Glück R. Dextran sulfate inhibits the fusion of influenza virus with model membranes, and suppresses influenza virus replicationin vivo. Antivir Res 1990;14:39–50.

    PubMed  Google Scholar 

  10. Kim KS, Sapienza VJ, Carp RI. Antiviral activity of arildone on deoxyribo-nucleic acid and ribonucleic acid viruses. Antimicrob Agents Chemother 1980;18:276–80.

    PubMed  Google Scholar 

  11. Badger J, Minor I, Kremer MJ, Oliveira MA, Smith TJ, Griffith JP, et al. Structural analysis of a series of antiviral agents complexed with human rhinovirus 14. Proc Natl Acad Sci USA 1988;85:3304–8.

    PubMed  Google Scholar 

  12. Rossmann MG. Antiviral agents targeted to interact with viral capsid proteins and a possible application to human immunodeficiency virus. Proc Natl Acad Sci USA 1988;85:4625–7.

    PubMed  Google Scholar 

  13. Yarchoan R, Perno CF, Thomas RV, Klecker RW, Allain J-P, Wills RJ, et al. Phase I studies of 2′,3′- dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine (AZT). Lancet 1988;1:76–81.

    PubMed  Google Scholar 

  14. Merigan TC, Skowron G, Bozette SA, Richman D, Uttamchandani R, Fischl M, et al. Circulating p24 antigen levels and responses to dideoxycytidine in human immunodeficiency virus (HIV) infections. Ann Intern Med 1989;110:189–94.

    PubMed  Google Scholar 

  15. Yarchoan R, Pluda JM, Thomas RV, Mitsuya H, Brouwers P, Wyvill KM, et al. Long term toxicity/activity profile of 2′,3′-dideoxyinosine in AIDS or AIDS-related complex. Lancet 1990;336:526–9.

    PubMed  Google Scholar 

  16. Ho H-T, Hitchcock MJM. Cellular pharmacology of 2′,3′-dideoxy-2′,3′-didehydrothymidine, a nucleoside analog active against humanimmunodeficiency virus. Antimicrob Agents Chemother 1989;33:844–9.

    PubMed  Google Scholar 

  17. Lake-Bakaar DM, Lindborg B, Datema R. Improvement of the absorption of oral (R,S)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine, an anti-varicella-zoster virus drug, in rats and monkeys. Antimicrob Agents Chemother 1989;33:110–2.

    PubMed  Google Scholar 

  18. Carter WA, Strayer DR, Brodsky I, Lewin M, Pellegrino MG, Einck L, et al. Clinical, immunological and virological effects of ampligen, a mismatched double-stranded RNA, in patients with AIDS or AIDS-related complex. Lancet 1987;1:1286–92.

    PubMed  Google Scholar 

  19. Karpas A, Fleet GWJ, Dwek RA, Petursson S, Namgoong SK, Ramsden NG, et al. Aminosugar derivatives as potential anti-human immunodeficiency virus agent. Proc Natl Acad Sci USA 1988;85:9229–33.

    PubMed  Google Scholar 

  20. Lang J-M, Touraine J-L, Trepo C. Randomised, double-bind, placebo controlled trial of dithiocarb sodium (“Imuthiol”) in human immunodeficiency virus infection. Lancet 1988;2:702–6.

    PubMed  Google Scholar 

  21. Reisinger EC, Kern P, Ernst M, Bock P, Flad HD, Dietrich M, et al. Inhibition of HIV progression by dithiocarb. Lancet 1990;335:679–82.

    PubMed  Google Scholar 

  22. Fischl MA, Parker CB, Pettinelli C, Wulfsohn M, Hirsch MS, Collier AC, et al. A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. N Engl J Med 1990;323:1009–14.

    PubMed  Google Scholar 

  23. Collier AC, Bozzette S, Coombs RW, Causey DM, Schoenfeld DA, Spector SA, et al. A pilot study of low-dose zidovudine in human immunodeficiency virus infection. N Engl J Med 1990;323:1015–21.

    PubMed  Google Scholar 

  24. Larder BA, Darby G, Richman DD. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 1989;243:1731–4.

    PubMed  Google Scholar 

  25. Hammer SM, Gillis JM. Synergistic activity of granulocyte-macrophage colony-stimulating factor and 3′-azido-3′-deoxythymidine against human immunode-ficiencyvirusin vitro. Antimicrob Agents Chemother 1987;31:1046–50.

    PubMed  Google Scholar 

  26. Baldwin GC, Fuller ND, Roberts RL, Ho DD, Golde DW. Granulocyte- and granulocyte-macrophage colony-stimulating factors enhance neutrophil cytotoxicity toward HIV-infected cells. Blood 1989;74:1673–7.

    PubMed  Google Scholar 

  27. Hardy WD, Spector S, Polsky B, Crumpacker C, Holland G, Freeman W, et al. Combined ganciclovir (GCV) and recombinant humangranulocyte-macro-phage-stimulating factor (GM-CSF) vs ganciclovir alone for cytomegalovirus (CMV) retinitis in AIDS, [Abstract]. Thirtieth Interscience Conference on Antimicrobial Agents and Chemotherapy, 1990; New Orleans, abstract 9.

  28. Freitas VR, Frase-Smith EB, Matthews TR. Increased efficacy of ganciclovir in combination with foscarnet against cytomegalovirus and herpes simplex virus type 2in vitro andin vivo. Antiviral Res 1989;12:205–12.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wiltink, E.H.H. Future prospects in antiviral therapy. Pharmaceutisch Weekblad Scientific Edition 14, 268–274 (1992). https://doi.org/10.1007/BF01962549

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01962549

Keywords

Navigation