HIV-1 Reverse Transcriptase (RT) is a multifunctional enzyme responsible for the transcription of the RNA genome of the HIV virus into DNA suitable for incorporation within the DNA of human host cells. Its crucial role in the viral life cycle has made it one of the major targets for antiretroviral drug therapy. The Non-Nucleoside RT Inhibitor (NNRTI) class of drugs binds allosterically to the e...

Inhibitors of the excision reaction catalysed by HIV-1 RT (reverse transcriptase) represent a promising approach in the fight against HIV, because these molecules would interfere with the main mechanism of resistance of this enzyme towards chain-terminating nucleotides. Only a limited number of compounds have been demonstrated to inhibit this reaction to date, including NNRTIs (non-nucleoside R...

HIV-1 RT is one of the key enzymes in the duplication of HIV-1. Inhibitors of HIV-1 RT are classified as nonnucleoside RT inhibitors (NNRTIs) and nucleoside analogues. NNRTIs bind in a region not associated with the active site of the enzyme. Within the NNRTI category, there is a set of inhibitors commonly referred to as TIBO inhibitors. Fifty TIBO inhibitors were used in the work to build 3-D ...

BACKGROUND Transposable Elements (TEs) comprise nearly 45% of the entire genome and are part of sophisticated regulatory network systems that control developmental processes in normal and pathological conditions. The retroviral/retrotransposon gene machinery consists mainly of Long Interspersed Nuclear Elements (LINEs-1) and Human Endogenous Retroviruses (HERVs) that code for their own endogeno...

Understanding the molecular mechanisms of HIV-1 reverse transcriptase (RT) action and drug inhibition is essential for designing effective antiretroviral therapies. Although comparisons of the different crystal forms of RT give insights into the flexibility of different domains, a direct computational assessment of the effect of inhibitor binding on the collective dynamics of RT is lacking. A s...

Background. The Russian HIV-1 epidemic is caused by several virus variants with strong founder effects. The most common variant, subtype A-FSU (Former Soviet Union), which began spreading among intravenous drug users in the 1990s, causes most of the 800,000 Russian infections. The spectrum of drug-resistance mutations (DRMs) in ARV-treated patients with this strain has not been studied. Methods...

A series of 2'-substituted cyclobutyl nucleoside analogs were efficiently prepared by constructing the core cyclobutyl ring using different [2+2] cycloaddition approaches. The triphosphate derivative of a cyclobutyl nucleoside was also synthesized and evaluated against wild-type and mutant HIV reverse transcriptases (RT). Whereas the nucleoside analogs were inactive against HIV-1 in culture, th...

pulmonary hypertension is rare but is one of the complications that occur due to hiv infection. symptoms of hiv-associated pulmonary arterial hypertension are often non-specific but the main symptom of the disease is dyspnea. in this cross-sectional study, we measured systolic pulmonary arterial pressure (spap) by echocardiographic methods among hiv-positive patients who received art. this rese...

in this study the uptake and metabolism of adenosine by mitochondria has been investigated. incubation of cem cells mitochondria preparation with [3h] -adenosine showed substantial uptake and metabolism of adenosine. adenosine was both anabolized to amp, adp and atp, and also catabolized to inosine. the highest concentration of metabolites in extracted mitochondria was due to amp. the mitochond...

Inspired by our previous efforts to improve the drug-resistance profiles of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs), a novel series “dual-site” binding diarylpyrimidine (DAPY) derivatives targeting both NNRTI adjacent site and NNRTIs pocket (NNIBP) were designed, synthesized, evaluated for their anti-HIV potency in TZM-bl MT-4 cells. Eight compounds exhibited moderate exc...