Use of virtual screening for discovering antiretroviral compounds interacting with the HIV-1 nucleocapsid protein.
The HIV-1 nucleocapsid protein (NC) is considered as an emerging drug target for the therapy of AIDS. Several studies have highlighted the crucial role of NC within the viral replication cycle. However, although NC inhibition has provided in vitro and in vivo antiretroviral activity, drug-candidates which interfere with NC functions are still missing in the therapeutic arsenal against HIV. Based on previous studies, where the dynamic behavior of NC and its ligand binding properties have been investigated by means of computational methods, here we used a virtual screening protocol for discovering novel antiretroviral compounds which interact with NC. The antiretroviral activity of virtual hits was tested in vitro, whereas biophysical studies elucidated the direct interaction of most active compounds with NC(11-55), a peptide corresponding to the zinc finger domain of NC. Two novel antiretroviral small molecules capable of interacting with NC are presented here.
Università di Roma La Sapienza, Dipartimento di Chimica e Tecnologie del Farmaco, piazzale A. Moro 5, I-00185 Roma, Italy.
Mattia
M
Mori
Patrizia
P
Schult-Dietrich
Beata
B
Szafarowicz
Nicolas
N
Humbert
Francois
F
Debaene
Sarah
S
Sanglier-Cianferani
Ursula
U
Dietrich
Yves
Y
Mély
Maurizio
M
Botta
D019380:Anti-HIV Agents / Q000302:isolation & purification* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015497:HIV-1 / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors*
D019380:Anti-HIV Agents; C071884:NCP7 protein, Human immunodeficiency virus 1; D054301:gag Gene Products, Human Immunodeficiency Virus