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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
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Antiviral nucleoside analogs.

Vladimir E Kataev1, Bulat F Garifullin1

  • 1Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Akademika Arbuzova St., Kazan, 420088 Tatarstan Russia.

Chemistry of Heterocyclic Compounds
|May 19, 2021
PubMed
Summary

This review covers nucleoside analog synthesis, focusing on prodrugs for cell entry and activation. It lists approved antivirals for HIV, hepatitis, and influenza, plus emerging SARS-CoV-2 therapies like remdesivir.

Keywords:
antiviral activitynucleoside analogspronucleotides

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Area of Science:

  • Medicinal Chemistry
  • Virology
  • Drug Discovery

Background:

  • Native nucleosides can be modified to create diverse nucleoside analogs.
  • Nucleoside analogs are crucial in antiviral therapy, targeting viral replication.
  • Prodrug strategies enhance cellular uptake and metabolic activation of nucleoside analogs.

Purpose of the Study:

  • To review the synthesis and applications of nucleoside analogs.
  • To highlight prodrug strategies for nucleoside analog delivery.
  • To catalog antiviral nucleoside analogs used for HIV, hepatitis B, C, influenza, and coronaviruses.

Main Methods:

  • Literature review of nucleoside analog synthesis.
  • Analysis of prodrug design for nucleoside analogs.
  • Compilation of approved and investigational antiviral nucleoside analogs.

Main Results:

  • Extensive libraries of nucleoside analogs with varied structures have been synthesized.
  • Prodrug forms facilitate cell penetration and conversion to active triphosphate metabolites.
  • Numerous cyclic nucleoside analogs are approved for treating viral infections like HIV, hepatitis B/C, and influenza.
  • Emerging nucleoside analogs show promise against SARS-CoV and MERS-CoV, with remdesivir approved for COVID-19.

Conclusions:

  • Nucleoside analog modification and prodrug synthesis are vital for developing effective antiviral agents.
  • The development of nucleoside analogs has significantly impacted the treatment of major viral diseases.
  • Ongoing research continues to yield novel nucleoside analogs with potential against emerging viral threats.