Abstract Coxsackievirus B3 is the main cause of human viral myocarditis and cardiomyopathy. Virally encoded Coxsackievirus 3C protease (3C pro ) plays an essential role in viral proliferation. Here, benserazide was discovered as a novel inhibitor from a drug library screen targeting Coxsackievirus 3C pro using a FRET-based enzyme assay. Benserazide, whose chemical structure has no electrophilic functional groups, was characterized as a non-competitive inhibitor by enzyme kinetic studies. A molecular docking study with benserazide and its analogs indicated that a novel putative allosteric binding site was involved. Specifically, a 2,3,4-trihydroxybenzyl moiety was determined to be a key pharmacophore for the enzyme's inhibitory activity. We suggest that the putative allosteric binding site may be a novel target for future therapeutic strategies.
Kim, B. K., Cho, J. H., Jeong, P., Lee, Y., Lim, J. J., Park, K. R., … Kim, Y. C. (2015). Benserazide, the first allosteric inhibitor of Coxsackievirus B3 3C protease. FEBS Letters, 589(15), 1795–1801. https://doi.org/10.1016/j.febslet.2015.05.027