The protease from simian immunodeficiency virus (SIV) was chemically synthesized by automated solid-phase technology as an NH2-terminally extended derivative, capped with biotin. Biotin-linker-(SIV protease (1-99)): the linker segment, Gly-Gly-Asp-Arg-Gly-Phe-Ala-Ala, corresponds to the amino acid sequence preceding that of the protease in the SIV gag/pol precursor polyprotein. Accordingly, the...

L-696,474, an inhibitor of the HIV-1 protease, was discovered in extracts of the fungal culture Hypoxylon fragiforme (MF5511; ATCC 20995). L-696,474 is a novel cytochalasin with a molecular weight of 477 and an empirical formula of C30H39NO4. L-696,474 inhibited HIV-1 protease activity with an IC50 of 3 microM and the mode of inhibition was competitive with respect to substrate (apparent Ki = 1...

In this study, application of a new hybrid docking-quantitative structure activity relationship (QSAR) methodology to model and predict the HIV-1 protease inhibition activities of a series of newly synthesized chemicals is reported. This approach can provide valuable information about the most important chemical and structural features of the ligands that affect their inhibitory activities. Doc...

Molecular dynamics simulations are performed to investigate the dynamic properties of wild-type HIV-1 protease and its two multi-drug-resistant variants (Flap + (L10I/G48V/I54V/V82A) and Act (V82T/I84V)) as well as their binding with APV and DRV inhibitors. The hydrophobic interactions between flap and 80 s (80's) loop residues (mainly I50-I84' and I50'-I84) play an important role in maintainin...

OBJECTIVES This study evaluates the impact of specific HIV-1 protease-compensatory mutations (wild-type amino acids in non-B subtypes) on virological response to a first-line lopinavir/ritonavir-containing regimen in an HIV-1 subtype B-infected population. PATIENTS AND METHODS The prevalence of protease-compensatory mutations from 1997 to 2011 was calculated in 3063 drug-naive HIV-1 B-infecte...

HIV protease inhibitors must penetrate into cells to exert their action. Differences in the intracellular pharmacokinetics of these drugs may explain why some patients fail on therapy or suffer from drug toxicity. Yet, there is no information available on the intracellular levels of HIV protease inhibitors in HIV infected children, which is in part due to the large amount of sample that is norm...

Objective: HIV-1 has been a killer disease since two decades ago, while a potential cure has not yet discovered due to the fast mutations of the HIV1 enzymes,i.e reverse transcriptase, integrase, and protease. Apart of HIV-1, malaria has been the biggest cause of death in human and it is mostly found in the East part of Indonesia. There are some enzymes in the food vacuole of Plasmodium falcipa...

OBJECTIVES HIV-1 genotyping is widely accepted as a diagnostic tool to optimize therapy changes in patients whose antiretroviral regimen is failing. Phenotyping can substantially complement the information obtained from genotyping, especially in the presence of complex mutational patterns. However, drug susceptibility tests are laborious and require biosafety facilities. We describe the molecul...

OBJECTIVE To describe a syndrome of peripheral lipodystrophy (fat wasting of the face, limbs and upper trunk), hyperlipidaemia and insulin resistance in patients receiving potent HIV protease inhibitor therapy. DESIGN Cross-sectional study. SETTING Outpatient clinic of a university teaching hospital. PATIENTS HIV-infected patients either receiving at least one protease inhibitor (n=116) o...

Maturation of human immunodeficiency virus (HIV) depends on the processing of Gag and Pol polyproteins by the viral protease, making this enzyme a prime target for anti-HIV therapy. Among the protease substrates, the nucleocapsid-p1 (NC-p1) sequence is the least homologous, and its cleavage is the rate-determining step in viral maturation. In the other substrates of HIV-1 protease, P1 is usuall...