Molecular recognition in the human immunodeficiency virus capsid and antiviral design.
Many compounds able to interfere with HIV-1 infection have been identified; some 25 of them have been approved for clinical use. Current anti-HIV-1 therapy involves the use of drug cocktails, which reduces the probability of virus escape. However, many issues remain, including drug toxicity and the emergence of drug-resistant mutant viruses, even in treated patients. Therefore, there is a constant need for the development of new anti-HIV-1 agents targeting other molecules in the viral cycle. The capsid protein CA plays a key role in many molecular recognition events during HIV-1 morphogenesis and uncoating, and is eliciting increased interest as a promising target for antiviral intervention. This article provides a structure-based, integrated review on the CA-binding small molecules and peptides identified to date, and their effects on virus capsid assembly and stability, with emphasis on recent results not previously reviewed. As a complement, we present novel experimental results on the development and proof-of-concept application of a combinatorial approach to study molecular recognition in CA and its inhibition by peptide compounds.
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Rebeca
R
Bocanegra
Alicia
A
Rodríguez-Huete
Miguel Ángel
MÁ
Fuertes
Marta
M
Del Álamo
Mauricio G
MG
Mateu
D019380:Anti-HIV Agents / Q000302:isolation & purification* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D016655:HIV Core Protein p24 / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24