New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections

Chem Asian J. 2019 Nov 18;14(22):3962-3968. doi: 10.1002/asia.201900841. Epub 2019 Aug 7.

Abstract

Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. They can be considered as either (i) adenine analogues (3-deazaneplanocin A, galidesivir, GS-6620 and remdesivir) or (ii) guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). All eight owe their mechanism of action to hydrogen bonded base pairing with either (i) uracil or (ii) cytosine. Four out of the eight compounds (galidesivir, GS-6620, remdesivir and pyrazofurin) are C-nucleosides, and two of them (GS-6620, remdesivir) also contain a phosphoramidate part. The C-nucleoside and phosphoramidate (and for the adenine analogues the 1'-cyano group as well) may be considered as essential attributes for their antiviral activity.

Keywords: antivirals; ebola; hemorrhagic fever viruses; nucleoside analogues.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Adenine / therapeutic use
  • Amides / chemistry
  • Amides / metabolism
  • Amides / pharmacology
  • Amides / therapeutic use
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Base Pairing
  • Ebolavirus / drug effects
  • Guanine / analogs & derivatives*
  • Guanine / pharmacology
  • Guanine / therapeutic use
  • Hemorrhagic Fevers, Viral / drug therapy*
  • Humans
  • Nucleotides / chemistry
  • Nucleotides / therapeutic use
  • Phosphoric Acids / chemistry
  • Phosphoric Acids / therapeutic use
  • Pyrazines / chemistry
  • Pyrazines / metabolism
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use
  • Triazines / chemistry
  • Triazines / therapeutic use

Substances

  • Amides
  • Antiviral Agents
  • GS-6620
  • Nucleotides
  • Phosphoric Acids
  • Pyrazines
  • Triazines
  • Guanine
  • phosphoramidic acid
  • favipiravir
  • Adenine