Pharmacophore modeling and molecular docking led to the discovery of inhibitors of human immunodeficiency virus-1 replication targeting the human cellular aspartic acid-glutamic acid-alanine-aspartic acid box polypeptide 3

Giovanni Maga; Federico Falchi; Anna Garbelli; Amalia Belfiore; Myriam Witvrouw; Fabrizio Manetti; Maurizio Botta

doi:10.1021/jm8008844

Pharmacophore modeling and molecular docking led to the discovery of inhibitors of human immunodeficiency virus-1 replication targeting the human cellular aspartic acid-glutamic acid-alanine-aspartic acid box polypeptide 3

J Med Chem. 2008 Nov 13;51(21):6635-8. doi: 10.1021/jm8008844. Epub 2008 Oct 4.

Authors

Giovanni Maga¹, Federico Falchi, Anna Garbelli, Amalia Belfiore, Myriam Witvrouw, Fabrizio Manetti, Maurizio Botta

Affiliation

¹ Istituto di Genetica Molecolare, IGM-CNR, Via Abbiategrasso 207, I-27100 Pavia, Italy. maga@igm.cnr.it

PMID: 18834110
DOI: 10.1021/jm8008844

Abstract

HIV-1 replication has been inhibited by using a compound able to target the human cellular cofactor DEAD-box ATPase DDX3, essential for HIV-1 RNA nuclear export. This compound, identified by means of a computational protocol based on pharmacophoric modeling and molecular docking calculations, represents the first small molecule with such a mechanism of action and could lay the foundations for a pioneering approach for the treatment of HIV-1 infections.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Crystallography, X-Ray
DEAD-box RNA Helicases / antagonists & inhibitors*
DEAD-box RNA Helicases / chemistry
DEAD-box RNA Helicases / metabolism*
Drug Evaluation, Preclinical
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
HIV-1 / drug effects*
HIV-1 / enzymology*
Humans
Models, Molecular
Protein Structure, Tertiary
Virus Replication*

Substances

Enzyme Inhibitors
DDX3X protein, human
DEAD-box RNA Helicases