Drug design: new inhibitors for HIV-1 protease based on Nelfinavir as lead.

Article Details

Citation

Perez MA, Fernandes PA, Ramos MJ

Drug design: new inhibitors for HIV-1 protease based on Nelfinavir as lead.

J Mol Graph Model. 2007 Oct;26(3):634-42. Epub 2007 Mar 24.

PubMed ID
17459746 [ View in PubMed
]
Abstract

Nelfinavir (Viracept) is a potent, non-peptidic inhibitor of HIV-1 Protease, which has been marketed for the treatment of HIV infected patients. However, HIV-1 develops drug-resistance which decreases the affinity of Nelfinavir for the binding pocket of Protease. We present here three new variants of Nelfinavir, which we have designed with computational tools, with greater affinity for HIV-1 Protease than Nelfinavir itself. Accordingly, we have introduced rational modifications in Nelfinavir, optimizing its affinity to the most conserved amino acids in Protease, in order to increase the efficiency of the three new inhibitors. Minimization and molecular dynamics simulations have been carried out on four complexes, HIV-1 Protease with Nelfinavir and subsequently with the new inhibitors, respectively, in order to analyze the behavior of the systems. Additionally, we have calculated the binding free energy differences Protease:inhibitor, which gave us a quantitative idea of the new molecules inhibitory efficiency in silico.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
NelfinavirHIV-1 proteaseProteinHuman Immunodeficiency Virus
Yes
Inhibitor
Details