METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY
Abstract
Dilated cardiomyopathy as a consequence of myocarditis induced by Coxsackieviruses group B3 (CVB3) is a worldwide cause of morbidity
and death for which current therapies have shown only modest effectiveness. In the present study we tested the efficacy of a novel CVB3
small interfering RNA (siRNA), directed against the protease 2A genome region (siRNA 3626), alone or in combination with another recently
described protease 2A siRNA (siRNA 3541). siRNAs (400 nM) were delivered by lipofection to HeLa cells, which were then infected by
CVB3 and analyzed. Under optimized transfection conditions, siRNA 3626 markedly improved the viability of CVB3-infected HeLa cells.
This was due to a drastic reduction in the amounts of CVB3 genome, viral capsid protein VP1 and vital virions. Finally, the combination of
siRNA 3626/3541 did not potentiate the anti-CVB3 effect compared with an equimolar concentration of either siRNA. In conclusion, these
data show the potency of siRNA 3626 in downmodulating CVB3 infection together with the lack of any significant transfection-related toxicity.
In addition to placing the selected siRNA 3626 among the most effective anti-CVB3 agents so far described, these data fully justify
future attempts to further optimize the siRNA-mediated approach to CVB3-induced myocarditis.
