Monensin and salinomycin inhibited enterovirus 71 infection dose-dependently with IC50 values of 0.25 μM and 1.49 μM and selectivity indices of 139.84 and 28.13, respectively, by neutralizing endolysosomal pH and blocking viral entry and maturation.
Do the ionophore antibiotics monensin and salinomycin reduce enterovirus infection in human rhabdomyosarcoma cells?
Monensin and salinomycin exhibit broad-spectrum antiviral activity against enteroviruses in vitro by neutralizing endolysosomal pH, thereby inhibiting viral entry and maturation.
Effect estimate: IC50 0.25 μM for Monensin, IC50 1.49 μM for Salinomycin; Selectivity index 139.84 for Monensin, 28.13 for Salinomycin
Enteroviruses, which belong to the Picornaviridae family, are implicated in a variety of illnesses that range from mild to severe, with some infections potentially being life-threatening. Among these, Enterovirus 71 (EV71) is recognized as one of the most virulent members of the enterovirus genus. Currently, there are no effective treatments available for EV infections. Ionophore antibiotics are small, hydrophobic, and lipophilic molecules approved for use in veterinary medicine as anti-coccidial feed additives. Notably, ionophore antibiotics such as monensin (MON) and salinomycin (SAL) have shown antiviral activity against specific virus groups, although the modes of actions are not yet well understood. This study investigates the antiviral effects and mechanisms of MON and SAL against enteroviruses. Our findings reveal a dose-dependent reduction in EV71 infection, with 50% inhibitory concentrations of 0.25 μM for MON and 1.49 μM for SAL. Mechanistic investigations demonstrated that both agents primarily inhibit EV71 infection at the entry stage, independent of viral binding and internalization. Furthermore, these agents effectively neutralized low pH levels within endolysosomes, which was associated with a decrease in antiviral efficacy when acidic conditions were maintained in the medium. Additionally, both agents showed the ability to block viral maturation, which requires an acidic environment. The antiviral effects of MON and SAL were also observed against various serotypes of enteroviruses. In summary, MON and SAL exhibit antiviral efficacy by neutralizing endolysosomal pH during the viral entry process, suggesting a potential broad-spectrum antiviral strategy that could be applicable to other viruses with similar replication pathways.
Hsu et al. (Tue,) conducted a other in Enterovirus infection including EV71 and other enterovirus serotypes. Monensin and Salinomycin vs. DMSO (control) was evaluated on Reduction in EV71 viral infection and protein expression measured by TCID50 assay and Western blot analysis (IC50 0.25 μM for Monensin, IC50 1.49 μM for Salinomycin; Selectivity index 139.84 for Monensin, 28.13 for Salinomycin). Monensin and salinomycin inhibited enterovirus 71 infection dose-dependently with IC50 values of 0.25 μM and 1.49 μM and selectivity indices of 139.84 and 28.13, respectively, by neutralizing endolysosomal pH and blocking viral entry and maturation.