Computational Analysis of Amiloride Analogue Inhibitors of Coxsackievirus B3 RNA Polymerase.

ABSTRACT: Coxsackievirus B3 (CVB3) is a picornavirus that is responsible for a significant proportion of human myocarditis. However, no antiviral treatment is currently available to treat this disease or indeed any picornaviral infections. Previously it was shown that amiloride and its derivative 5-(N-ethyl-N-isopropyl)amiloride inhibit the in vitro enzymatic activity of CVB3 RNA polymerase (3D^pol). Here we measure and compare the inhibitory activity of ten amiloride analogues against CVB3 3D^pol. We show that replacement of the 3,5-diaminopyrazinyl moiety of amiloride causes loss of the inhibitory activity, whereas modifications at the 5-amino and guanidino groups increase or decrease potency. Importantly, a combination of substitutions at both the 5

SUBMITTER: Holien JK 

PROVIDER: S-EPMC4610404 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature