Pharmaceuticals (May 2024)

Small Molecule Drugs Targeting Viral Polymerases

  • Deborah Palazzotti,
  • Martina Sguilla,
  • Giuseppe Manfroni,
  • Violetta Cecchetti,
  • Andrea Astolfi,
  • Maria Letizia Barreca

DOI
https://doi.org/10.3390/ph17050661
Journal volume & issue
Vol. 17, no. 5
p. 661

Abstract

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Small molecules that specifically target viral polymerases—crucial enzymes governing viral genome transcription and replication—play a pivotal role in combating viral infections. Presently, approved polymerase inhibitors cover nine human viruses, spanning both DNA and RNA viruses. This review provides a comprehensive analysis of these licensed drugs, encompassing nucleoside/nucleotide inhibitors (NIs), non-nucleoside inhibitors (NNIs), and mutagenic agents. For each compound, we describe the specific targeted virus and related polymerase enzyme, the mechanism of action, and the relevant bioactivity data. This wealth of information serves as a valuable resource for researchers actively engaged in antiviral drug discovery efforts, offering a complete overview of established strategies as well as insights for shaping the development of next-generation antiviral therapeutics.

Keywords