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

Ajay Kumar Timiri, Syed Hussain Basha, Rana Abdelnabi, Johan Neyts, Pieter Leyssen, Barij Nayan Sinha, Venkatesan Jayaprakash

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.

Keywords


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

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References


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DOI: http://dx.doi.org/10.14805/jphchem.2017.art83

DOI (PDF): http://dx.doi.org/10.14805/jphchem.2017.gal41

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