Novel Synergistic Anti-Enteroviral Drug Combinations

Viruses. 2022 Aug 25;14(9):1866. doi: 10.3390/v14091866.


Background: Enterovirus infections affect people around the world, causing a range of illnesses, from mild fevers to severe, potentially fatal conditions. There are no approved treatments for enterovirus infections. Methods: We have tested our library of broad-spectrum antiviral agents (BSAs) against echovirus 1 (EV1) in human adenocarcinoma alveolar basal epithelial A549 cells. We also tested combinations of the most active compounds against EV1 in A549 and human immortalized retinal pigment epithelium RPE cells. Results: We confirmed anti-enteroviral activities of pleconaril, rupintrivir, cycloheximide, vemurafenib, remdesivir, emetine, and anisomycin and identified novel synergistic rupintrivir-vemurafenib, vemurafenib-pleconaril and rupintrivir-pleconaril combinations against EV1 infection. Conclusions: Because rupintrivir, vemurafenib, and pleconaril require lower concentrations to inhibit enterovirus replication in vitro when combined, their cocktails may have fewer side effects in vivo and, therefore, should be further explored in preclinical and clinical trials against EV1 and other enterovirus infections.

Keywords: antiviral drug combination; antiviral strategy; broad-spectrum antiviral agent; echovirus; enterovirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anisomycin / therapeutic use
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Cycloheximide / therapeutic use
  • Drug Combinations
  • Emetine
  • Enterovirus Infections*
  • Humans
  • Picornaviridae*
  • Vemurafenib / therapeutic use


  • Antiviral Agents
  • Drug Combinations
  • Vemurafenib
  • Anisomycin
  • Cycloheximide
  • Emetine

Grants and funding

This research was funded by the European Regional Development Fund, the Mobilitas Pluss Project grant MOBTT39.