Autor(es): Nguyen Phuong T V, Yu Haibo, Keller Paul A

Resumo: The recent emergence - re-emergence of alphaviruses, in particular the chikungunya virus (CHIKV), in numerous countries has invoked a worldwide threat to human health, while simultaneously generating an economic burden on affected countries. There are currently no vaccines or effective drugs available for the treatment of the CHIKV, - with few lead compounds reported, the vital medicinal chemistry is significantly more challenging. This study reports on the discovery of potential inhibitors for the nsP3 macro domain of CHIKV using molecular docking, virtual screening, - molecular dynamics simulations, as well as work done to evaluate - confirm the active site of nsP3. Virtual screening was carried out based on blind docking as well as focused docking, using the database of 1541 compounds from NCI Diversity Set II, to identify hit compounds for nsP3. The top hit compounds were further subjected to molecular dynamic simulations, yielding a greater underst-ing of the dynamic behavior of nsP3 - its complexes with various lig-s, concurrently confirming the outcomes of docking, - establishing in silico lead compounds which target the CHIKV nsP3 enzyme.

Palavras-Chave: Chikungunya virus; Molecular docking; Virtual screening; Molecular dynamics simulations nsP3 macro domain

Imprenta: Journal of Molecular Modeling, v. 20, n. 5, p. 2216, 2014

Identificador do objeto digital: 10.1007/s00894-014-2216-6

Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Molecular structure ; Chikungunya virus - Proteins ; Chikungunya Virus - Virus ; Chikungunya virus - Molecular screening ; Chikungunya virus - Vaccine ; Chikungunya virus - Public health

Data de publicação: 2014

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