Advertisement

Pharmacological considerations of antiviral agents

  • W. H. Prusoff
  • T -S Lin
  • S. A. Siegel
  • M. L. Zucker
  • W. F. BrubakerJr
  • J. J. Lee
Chapter

Abstract

Among the various questions that may be raised in a discussion of pharmacological considerations relative to antiviral agents, we may include: (1) How does one design an effective but non-toxic antiviral agent? (2) Can we deliver the drug to the target site and maintain an antiviral concentration for the required period of time? (Here we are concerned with absorption, distribution, metabolism and excretion of the drug.) (3) How can we avoid or minimize the emergence of a resistant population of virus? (4) How can we prevent the virus from going into the latent state, but once there how can we control its reactivation?

Keywords

Trigeminal Ganglion Antiviral Agent Purine Nucleoside Phosphorylase Trigeminal Ganglion Neurone Pyrimidine Nucleoside 
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. CHENG, Y.C. & PRUSOFF, W.H. (1974). Mouse ascites sarcoma 180 deoxythymidine kinase: General properties and inhibition studies. Biochemistry, 13, 1179–1185.Google Scholar
  2. DARBY, G. & FIELD, H.J. (1984). Latency and acquired resistance — problems in chemotherapy of herpes infections. Pharmac. Ther., 23, 217–251.Google Scholar
  3. DESGRANGES, C., RAZAKA, G., DROUILLET, F., BRICAUD, H., HERDEWIJN, P. & DECLERCQ, E. (1984). Regeneration of the antiviral drug (E)-5-(2bromovinyl)-2′-deoxyuridine in vivo. NucleicAcid Res., 12, 2081–2090.Google Scholar
  4. FISCHER, P.H., LEE, J.J., CHEN, M.S., LIN, T.S. & PRUSOFF, W.H. (1979). Synergistic effect of 5′-amino-5′-deoxythymidine and 5-iodo-2′-deoxyuridine against herpes simplex virus infections in vitro. Biochem. Pharmac., 28, 3483–3486.Google Scholar
  5. FISCHER, P.H., CHEN, M.S. & PRUSOFF, W.H. (1980). The incorporation of 5-iodo-5′-amino-2′,5′-dideoxyuridine and 5-iodo-2′-deoxyuridine into herpes simplex virus DNA: A relationship to their antiviral activity and effects on DNA structure. Biochim. Biophys. Acta, 606, 236–245.Google Scholar
  6. FOX, J.S. & WHITE, D.O. (1980). Delivery of antiviral chemotherapeutic agents to neurons by retrograde axonal transport. Medical Hypothesis, 6, 773–779. HARMENBERG, J. (1983). Intracellular pools of thymidine reduce the antiviral action of acyclovir. Intervirol., 20, 48–51.Google Scholar
  7. MANCINI, W.R., DECLERCQ, E. & PRUSOFF, W.H. (1983). The relationship between incorporation of E-5-(2-bromovinyl)-2′-deoxyuridine into herpesvirus type 1 DNA with virus infectivity and DNA integrity. J. biol. Chem., 258, 123–138.Google Scholar
  8. OTTO, M.J. & PRUSOFF, W.H. (1984). The relationship between the antiviral activity of 5′-amino-5′-deoxythymidine and its incorporation into herpes simplex virus type 1 DNA. Antiviral Res. (in press).Google Scholar
  9. PRUSOFF, W.H. & OTTO, M.J. (1983). Problems in the pharmacology and pharmacokinetics of antivirals. In Problems of Antiviral Therapy, Stuart-Harris & Oxford, J. (eds), pp. 125–148, London: Academic Press.Google Scholar
  10. PRUSOFF, W.H., LIN, T-S., MANCINI, W.R., OTTO, M.J., SIEGEL, S.A. & LEE, J.J. (1984a). Overview of the possible targets for viral chemotherapy. In Targets for the Design of Antiviral Agents, Walker, R. & DeClercq, E. (eds), pp. 1–27, New York: Plenum Publishing Corporation.Google Scholar
  11. PRUSOFF, W.H., MANCINI, W.R., SIEGEL, S.A., LIN, T-S., LEE, J.J. & ZUCKER, M.L. (1984b). Molecular basis for treatment of herpesvirus infections. In Herpesvirus, UCLA Symposia on Molecular and Cellular biology, New Series, Volume 21, Rapp, F. (ed.), New York: Alan R. Liss, Inc. (in press).Google Scholar
  12. PRUSOFF, W.H., MANCINI, W.R., LIN, T.-S., LEE, J.J., SIEGEL, S.A. & OTTO, M.J. (1984c). Physical and biological consequences of incorporation of antiviral agents into virus DNA. Antiviral Res. (in press).Google Scholar
  13. TUTTLE, J.V. & KRENITSKY, T.A. (1984). Effects of acyclovir and its metabolites on purine nucleoside phosphorylase. J. biol. Chem., 259, 4065–4069.Google Scholar

Copyright information

© Macmillan Publishers Limited 1984

Authors and Affiliations

  • W. H. Prusoff
    • 1
  • T -S Lin
  • S. A. Siegel
  • M. L. Zucker
  • W. F. BrubakerJr
  • J. J. Lee
  1. 1.Department of PharmacologyYale University School of MedicineNew HavenUSA

Personalised recommendations