Identification of Broad-Spectrum Dengue/Zika Virus Replication Inhibitors by Functionalization of Quinoline and 2,6-Diaminopurine Scaffolds

ChemMedChem. 2018 Jul 18;13(14):1371-1376. doi: 10.1002/cmdc.201800178. Epub 2018 Jun 1.

Abstract

Social and demographic changes across the world over the past 50 years have resulted in significant outbreaks of arboviruses such as dengue virus (DENV) and Zika virus (ZIKV). Despite the increased threat of infection, no approved drugs or fully protective vaccines are available to counteract the spread of DENV and ZIKV. The development of "broad-spectrum" antivirals (BSAs) that target common components of multiple viruses can be a more effective strategy to limit the rapid emergence of viral pathogens than the classic "one-bug/one-drug" approach. Starting from previously identified multitarget DENV inhibitors, herein we report the identification of novel 2,6-diaminopurine derivatives that are able to block the replication of both Zika virus and all serotypes of dengue virus (DENV 1-4) in infected cells.

Keywords: 2,6-diaminopurines; broad-spectrum antivirals; co-infections; dengue; zika.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Aminopurine / analogs & derivatives*
  • 2-Aminopurine / chemistry
  • 2-Aminopurine / pharmacology
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Coinfection / drug therapy
  • Dengue / drug therapy
  • Dengue Virus / drug effects*
  • Drug Design
  • Drug Discovery
  • Humans
  • Models, Molecular
  • Quinolines / chemistry*
  • Quinolines / pharmacology*
  • Virus Replication / drug effects
  • Zika Virus / drug effects*
  • Zika Virus Infection / drug therapy

Substances

  • Antiviral Agents
  • Quinolines
  • 2-Aminopurine
  • 2,6-diaminopurine