期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 91, 期 -, 页码 72-90出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2014.09.099
关键词
Variola virus; Thymidylate kinase; Smallpox; Docking; Molecular dynamics
资金
- Brazilian financial agency Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [304557/2012-9, 474757/2012-9]
- Brazilian financial agency Fundacao de Amparo ao Ensino e Pesquisa do Estado do Rio de Janeiro (FAPERJ) [E-26/102.993/2012]
- Brazilian financial agency Fundacao de Amparo ao Ensino e Pesquisa de Minas Gerais (FAPEMIG) [PPM-00499-13, PPM-00434-13]
- Brazilian financial agency Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/Ministerio da Defesa (CAPES/MD) [PD 1782/2008]
Recently we constructed a homology model of the enzyme thymidylate kinase from Variola virus (VarTMPK) and proposed it as a new target to the drug design against smallpox. In the present work, we used the antivirals cidofovir and acyclovir as reference compounds to choose eleven compounds as leads to the drug design of inhibitors for VarTMPK. Docking and molecular dynamics (MD) studies of the interactions of these compounds inside VarTMPK and human TMPK (HssTMPK) suggest that they compete for the binding region of the substrate and were used to propose the structures of ten new inhibitors for VarTMPK. Further docking and MD simulations of these compounds, inside VarTMPK and HssTMPK, suggest that nine among ten are potential selective inhibitors of VarTMPK. (C) 2014 Elsevier Masson SAS. All rights reserved.
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