A Preclinical Assessment To Repurpose Drugs To Target Type 1 Diabetes-Associated Type B Coxsackieviruses

Aim To screen several antiviral drugs systematically for their efficacy against type B coxsackieviruses. Methods Ten drugs with different antiviral mechanisms were analysed for their efficacy against prototype strains of type B coxsackieviruses in A549 cells. Cell viability was quantified in fixed cells using a colorimetric assay. Median effective dose was interpolated from the triplicated experiments and the dose-response curves were generated for each drug-virus combination. Drug cytotoxicity was similarly quantified and selectivity indices calculated. Results Hizentra, pleconaril, fluoxetine, norfluoxetine, ribavirin, favipiravir, and guanidine hydrochloride were able to abrogate infection by all tested viruses, with the exception of complete inefficacy of pleconaril against coxsackievirus B3 and favipiravir against coxsackievirus B2. The effective doses for Hizentra, enviroxime, ribavirin, favipiravir, and pleconaril were clearly below their therapeutic serum concentrations, while the effective concentrations of fluoxetin, norfluoxetine and itraconazole exceeded their therapeutic serum concentrations. Lovastatin and azithromycin did not efficiently block type B coxsackieviruses. Conclusion Hizentra, enviroxime, pleconaril, ribavirin, and favipiravir are effective against type B coxsackievirusesin vitroin their therapeutic serum concentrations. These antiviral drugs are therefore attractive candidates for type 1 diabetes prevention/treatment trials. They can also be used in other clinical conditions caused by type B coxsackieviruses.