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- Title
A preclinical assessment to repurpose drugs to target type 1 diabetes‐associated type B coxsackieviruses.
- Authors
Sioofy‐Khojine, A. B.; Honkimaa, A.; Hyöty, H.
- Abstract
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 coxsackieviruses in vitro in 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. What's new?: Type B coxsackieviruses are associated with type 1 diabetes.Although many drugs have shown anti‐enterovirus properties, no antiviral drug has currently been licensed specifically for the treatment of enterovirus infections.Repurposing antiviral drugs represent an attractive opportunity in type 1 diabetes prevention trials.Dose and spectrum tests against type B coxsackieviruses showed that Hizentra, enviroxime, ribavirin, pleconaril and favipiravir would be the best candidates for this strategy.Ribavirin and itraconazole were less effective but were able to impair virus replication.Our results can be used to design clinical trials aimed at eradication from the pancreas of persistent infection and preventing/treating type 1 diabetes.Using antiviral drugs to treat children with type 1 diabetes will help to elucidate the involvement of enteroviruses, including coxsackieviruses, over the course of the condition.
- Subjects
ANTIVIRAL agents; CELL lines; COLORIMETRY; COXSACKIEVIRUSES; DRUG design; DOSE-effect relationship in pharmacology; CLINICAL drug trials; DRUG toxicity; FLUOXETINE; TYPE 1 diabetes; ORGANIC compounds; RIBAVIRIN; CELL survival; IN vitro studies; ITRACONAZOLE; PHARMACODYNAMICS
- Publication
Diabetic Medicine, 2020, Vol 37, Issue 11, p1849
- ISSN
0742-3071
- Publication type
Article
- DOI
10.1111/dme.14175