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

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.