Advances in Nucleoside and Nucleotide Analogues in Tackling Human Immunodeficiency Virus and Hepatitis Virus Infections

ChemMedChem. 2021 May 6;16(9):1403-1419. doi: 10.1002/cmdc.202000849. Epub 2021 Feb 12.

Abstract

Nucleoside and nucleotide analogues are structurally similar antimetabolites and are promising small-molecule chemotherapeutic agents against various infectious DNA and RNA viruses. To date, these analogues have not been documented in-depth as anti-human immunodeficiency virus (HIV) and anti-hepatitis virus agents, these are at various stages of testing ranging from pre-clinical, to those withdrawn from trials, or those that are approved as drugs. Hence, in this review, the importance of these analogues in tackling HIV and hepatitis virus infections is discussed with a focus on the viral genome and the mechanism of action of these analogues, both in a mutually exclusive manner and their role in HIV/hepatitis coinfection. This review encompasses nucleoside and nucleotide analogues from 1987 onwards, starting with the first nucleoside analogue, zidovudine, and going on to those in current clinical trials and even the drugs that have been withdrawn. This review also sheds light on the prospects of these nucleoside analogues in clinical trials as a treatment option for the COVID-19 pandemic.

Keywords: HIV; hepatitis; mechanism of drug action; nucleosides; nucleotides; viral genome; viral polymerases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • COVID-19 / epidemiology
  • COVID-19 Drug Treatment
  • Clinical Trials as Topic
  • Drug Repositioning
  • HIV / drug effects
  • HIV / enzymology
  • HIV Infections / drug therapy*
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • Hepatitis Viruses / drug effects
  • Hepatitis Viruses / enzymology
  • Hepatitis, Viral, Human / drug therapy*
  • Humans
  • Nucleosides / therapeutic use*
  • Nucleotides / therapeutic use*
  • Pandemics
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors
  • Reverse Transcriptase Inhibitors / therapeutic use
  • SARS-CoV-2 / drug effects

Substances

  • Anti-HIV Agents
  • Nucleosides
  • Nucleotides
  • Reverse Transcriptase Inhibitors
  • RNA-Dependent RNA Polymerase
  • HIV Reverse Transcriptase