Docking and QM/MM Studies of NS2B-NS3pro Inhibitors: a Molecular Target against the Dengue Virus

AUTOR(ES)

Godói, Isabella P., Lima, William Gustavo, Comar Junior, Moacyr, Alves, Ricardo José, Ferreira, Jaqueline Maria S., Kong, De-Xin, Taranto, Alex G.

FONTE

J. Braz. Chem. Soc.

DATA DE PUBLICAÇÃO

2017-05

RESUMO

Dengue virus (DENV) has been characterized as having great clinical importance in the world, as there is no specific treatment against this virus. The NS2B-NS3pro complex is essential for the replication and maturation of DENV and is a potential pharmacological target. The present study aims to evaluate and understand the interactions and affinities (via molecular docking/AutoDock Vina) of 16 peptidomimetic derivatives applied to a NS2B-NS3pro DENV-2 complex constructed by homology modeling (via SWISS-MODEL). Two compounds were selected as potential inhibitors of this protein complex. In addition, these compounds possess important interactions involving Ser135, Gly169 and Tyr161, which have been described previously to be fundamental to the recognition of inhibitors directed to this receptor. Thus, the involvement of these residues is significant pharmacologically because they may contribute to the inhibitory action of this molecular target against DENV.

Documentos Relacionados

• Molecular dynamics simulations and QM/MM studies of the reactivation by 2-PAM of tabun inhibited human acethylcolinesterase
• Isotropic and anisotropic NMR chemical shifts in liquid water: a sequential QM/MM study
• Processing and localization of Dengue virus type 2 polyprotein precursor NS3-NS4A-NS4B-NS5.
• Cleavage of the dengue virus polyprotein at the NS3/NS4A and NS4B/NS5 junctions is mediated by viral protease NS2B-NS3, whereas NS4A/NS4B may be processed by a cellular protease.
• Chromophore Structure of Cyanobacterial Phytochrome Cph1 in the Pr State: Reconciling Structural and Spectroscopic Data by QM/MM Calculations