Benserazide, the first allosteric inhibitor of Coxsackievirus B3 3C protease

Bo Kyoung Kim, Joong Heui Cho, Pyeonghwa Jeong, Youngjin Lee, Jia Jia Lim, Kyoung Ryoung Park, Soo Hyun Eom, Yong Chul Kim

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Abstract Coxsackievirus B3 is the main cause of human viral myocarditis and cardiomyopathy. Virally encoded Coxsackievirus 3C protease (3Cpro) plays an essential role in viral proliferation. Here, benserazide was discovered as a novel inhibitor from a drug library screen targeting Coxsackievirus 3Cpro 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.

Original languageEnglish
Pages (from-to)1795-1801
Number of pages7
JournalFEBS Letters
Issue number15
Publication statusPublished - 8 Jul 2015
Externally publishedYes


  • 3C protease
  • Allosteric binding site
  • Benserazide
  • Coxsackievirus B3
  • Enzyme kinetics
  • Non-competitive inhibitor

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