Research Articles

In silico development of a novel putative inhibitor of the 3C protease of Coxsackievirus B3 with a benzene sulfonamide skeleton

Vol. 4 No. 3 (2017) 25-34 Published August 9, 2017

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Abstract

Availability of X-ray crystal structure of 3C protease of several enteroviruses provided an opportunity for in silico drug design and development approach. Presented study is aimed at designing a novel compound targeting 3C protease of Coxsackievirus (CVB3), which is reported frequently to cause myocarditis in North America and Europe. A pthalimido-sulfonamide derivative (ZINC13799063) was identified through high-throughput virtual screening (HTVS) approach from the top HITs. A small library of phalimido-sulphonamides was enumerated to find a potential LEAD. Compound 17 from the library was found to inhibit CVB3 selectively in cell based antiviral assay at a concentration of EC50=1.0±0.1 µM with a selectivity index of >140. Molecular dynamics study was performed to investigate the selective inhibition of CVB3 over CVB4.

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Timiri, A. K.; Hussain Basha, S.; Abdelnabi, R.; Neyts, J.; Leyssen, P.; Sinha, B. N.; Jayaprakash, V. In Silico Development of a Novel Putative Inhibitor of the 3C Protease of Coxsackievirus B3 With a Benzene Sulfonamide Skeleton. J Pharm Chem 2017, 4 (3), 25-34. https://doi.org/10.14805/jphchem.2017.art83.
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Received
July 29, 2017
Published
August 9, 2017
Section
Research Articles
Pages
25-34

Keywords

  • Coxsackie virus B3
  • Virtual Screening
  • protease inhibitors
  • Sulfonamide
  • Molecular dynamics

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