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.
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.
Maga
Giovanni
G
Istituto di Genetica Molecolare, IGM-CNR, Via Abbiategrasso 207, I-27100 Pavia, Italy. maga@igm.cnr.it
Falchi
Federico
F
Garbelli
Anna
A
Belfiore
Amalia
A
Witvrouw
Myriam
M
Manetti
Fabrizio
F
Botta
Maurizio
M
D018360:Crystallography, X-Ray; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D014779:Virus Replication
D004791:Enzyme Inhibitors; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases