Broad-Spectrum Flavivirus Inhibitors: a Medicinal Chemistry Point of View

ChemMedChem. 2020 Dec 15;15(24):2391-2419. doi: 10.1002/cmdc.202000464. Epub 2020 Oct 22.

Abstract

Infections by flaviviruses, such as Dengue, West Nile, Yellow Fever and Zika viruses, represent a growing risk for global health. There are vaccines only for few flaviviruses while no effective treatments are available. Flaviviruses share epidemiological, structural, and ecologic features and often different viruses can co-infect the same host. Therefore, the identification of broad-spectrum inhibitors is highly desirable either for known flaviviruses or for viruses that likely will emerge in the future. Strategies targeting both virus and host factors have been pursued to identify broad-spectrum antiflaviviral agents. In this review, we describe the most promising and best characterized targets and their relative broad-spectrum inhibitors, identified by drug repurposing/libraries screenings and by focused medicinal chemistry campaigns. Finally, we discuss about future strategies to identify new broad-spectrum antiflavivirus agents.

Keywords: Dengue; Medicinal chemistry; Zika; antiviral agents; flavivirus inhibitors.

Publication types

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

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / therapeutic use*
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / therapeutic use*
  • Flavivirus / chemistry
  • Flavivirus / drug effects*
  • Flavivirus / enzymology
  • Flavivirus Infections / drug therapy*
  • Humans

Substances

  • Antiviral Agents
  • Enzyme Inhibitors