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Acyclic nucleosides as antiviral compounds

S Freeman1, J M Gardiner

  • 1Department of Pharmacy, University of Manchester, UK.

Molecular Biotechnology
|April 1, 1996
PubMed
Summary
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Acyclic nucleosides like acyclovir are vital antiviral drugs. Prodrugs and novel analogs offer improved bioavailability and broader activity against viral infections, including HIV and herpesviruses.

Area of Science:

  • Virology
  • Medicinal Chemistry
  • Pharmacology

Background:

  • Acyclovir effectively treats herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections by inhibiting viral DNA polymerase.
  • Low oral bioavailability of acyclovir necessitates the development of prodrugs, such as valaciclovir for shingles treatment.
  • Ganciclovir targets cytomegalovirus (CMV), and famciclovir, a penciclovir prodrug, is also used for shingles.

Purpose of the Study:

  • To review the development and applications of acyclic nucleoside analogs in antiviral therapy.
  • To highlight novel compounds with activity against resistant viral strains and emerging viral diseases.
  • To explore the potential of acyclic nucleosides in combination therapies and other disease treatments.

Main Methods:

Related Experiment Videos

  • Review of existing literature on acyclic nucleoside antiviral drugs.
  • Discussion of drug mechanisms, including DNA polymerase inhibition and reverse transcriptase binding.
  • Exploration of prodrug strategies and novel analog development.

    • Main Results:

    • Acyclic nucleoside phosphonates like PMEA and (S)-HPMPC show promise against various herpesviruses and in HIV treatment.
    • (S)-HPMPC demonstrates significant in vivo activity against HSV, VZV, CMV, and Epstein-Barr virus (EBV).
    • Acyclic nucleoside-containing oligonucleotides offer nuclease resistance for potential antisense/antigene therapy.
    • HEPT targets HIV-1 reverse transcriptase, and some analogs inhibit nucleoside phosphorylase.

    Conclusions:

    • Acyclic nucleosides represent a versatile class of antiviral agents with diverse mechanisms and applications.
    • Prodrugs and novel analogs are crucial for enhancing efficacy and overcoming resistance.
    • These compounds hold therapeutic potential in treating viral infections, HIV, and potentially in combination cancer therapies.