scholarly journals Anti-HIV Drugs and Resistance: Inhibitors of HIV-1 Reverse Transcriptase and Protease

2012 ◽  
pp. 23-44
Author(s):  
Tomozumi Imamichi
Keyword(s):  
Reverse Transcriptase ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Hiv 1

Sensitivity of V75I HIV-1 reverse transcriptase mutant selected in vitro by acyclovir to anti-HIV drugs

AIDS ◽  
2010 ◽  
Vol 24 (2) ◽  
pp. 319-323 ◽  
Author(s):  
Moira A McMahon ◽  
Janet D Siliciano ◽  
Rahul M Kohli ◽  
Robert F Siliciano
Keyword(s):  
Reverse Transcriptase ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Predicting binding modes and affinities for non-nucleoside inhibitors to HIV-1 reverse transcriptase using molecular docking

2019 ◽  
Vol 2 (1) ◽  
pp. 53-58
Author(s):  
Nguyen Truong Tien ◽  
Bui Tho Thanh
Keyword(s):  
Molecular Docking ◽  
Reverse Transcriptase ◽  
Binding Pocket ◽  
The Body ◽  
Binding Modes ◽  
Weakly Bound ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Hiv Aids

The HIV/AIDS epidemic has become one of the most dangerous causes leading to millions of deaths around the world a year. To date, there have not had effective anti-HIV drugs in the treatment of HIV/AIDS because of emerging drug-resistant HIV mutants. In this work, potential non-nucleoside reverse transcriptase inhibitors (NNRTIs) were studied by means of molecular docking. The Diversity “drug-like” database from the National Cancer Institute, is composed of 1.420 compounds, was performed docking into the NNRTI binding pocket of HIV-1 reverse transcriptase crystal structure (1fk9) by using Autodock version 4.2.6. Pharmacokinetic properties (absorption, distribution, metabolism and excretion (ADME)) and toxicity of potential inhibitors within the body were predicted by the PreADMET version 2.0. The obtained results point out that the compound, coded 2518, was discovered as a potential inhibitor that has good human intestinal absorption, weakly bound to plasma proteins as well as is negative to mutagenicity and carcinogenicity. This rational inhibitor would be further studied in order to contribute informations finding new anti-HIV drugs.

PASS-based approach to predict HIV-1 reverse transcriptase resistance

2017 ◽  
Vol 15 (02) ◽  
pp. 1650040 ◽  
Author(s):  
Olga Tarasova ◽  
Dmitry Filimonov ◽  
Vladimir Poroikov
Keyword(s):  
Amino Acid ◽  
Reverse Transcriptase ◽  
Open Data ◽  
Amino Acid Substitutions ◽  
Hiv Reverse Transcriptase ◽  
Hiv Rt ◽  
Hiv Drugs ◽  
Rt Inhibitors ◽  
Anti Hiv ◽  
Hiv 1

HIV reverse transcriptase (RT) inhibitors targeting the early stages of virus–host interactions are of great interest to scientists. Acquired HIV RT resistance happens due to mutations in a particular region of the pol gene encoding the HIV RT amino acid sequence. We propose an application of the previously developed PASS algorithm for prediction of amino acid substitutions potentially involved in the resistance of HIV-1 based on open data. In our work, we used more than 3200 HIV-1 RT variants from the publicly available Stanford HIV RT and protease sequence database already tested for 10 anti-HIV drugs including both nucleoside and non-nucleoside RT inhibitors. We used a particular amino acid residue and its position to describe primary structure-resistance relationships. The average balanced accuracy of the prediction obtained in 20-fold cross-validation for the Phenosense dataset was about 88% and for the Antivirogram dataset was about 79%. Thus, the PASS-based algorithm may be used for prediction of the amino acid substitutions associated with the resistance of HIV-1 based on open data. The computational approach for the prediction of HIV-1 associated resistance can be useful for the selection of RT inhibitors for the treatment of HIV infected patients in the clinical practice. Prediction of the HIV-1 RT associated resistance can be useful for the development of new anti-HIV drugs active against the resistant variants of RT. Therefore, we propose that this study can be potentially useful for anti-HIV drug development.

scholarly journals Potent Synergistic Anti-Human Immunodeficiency Virus (HIV) Effects Using Combinations of the CCR5 Inhibitor Aplaviroc with Other Anti-HIV Drugs

2008 ◽  
Vol 52 (6) ◽  
pp. 2111-2119 ◽  
Author(s):  
Hirotomo Nakata ◽  
Seth M. Steinberg ◽  
Yasuhiro Koh ◽  
Kenji Maeda ◽  
Yoshikazu Takaoka ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Synergistic Effects ◽  
Immunodeficiency Virus ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Nonparametric Statistical ◽  
Anti Hiv ◽  
Ccr5 Inhibitor ◽  
Hiv 1

ABSTRACT Aplaviroc (AVC), an experimental CCR5 inhibitor, potently blocks in vitro the infection of R5-tropic human immunodeficiency virus type 1 (R5-HIV-1) at subnanomolar 50% inhibitory concentrations. Although maraviroc is presently clinically available, further studies are required to determine the role of CCR5 inhibitors in combinations with other drugs. Here we determined anti-HIV-1 activity using combinations of AVC with various anti-HIV-1 agents, including four U.S. Food and Drug Administration-approved drugs, two CCR5 inhibitors (TAK779 and SCH-C) and two CXCR4 inhibitors (AMD3100 and TE14011). Combination effects were defined as synergistic or antagonistic when the activity of drug A combined with B was statistically greater or less, respectively, than the additive effects of drugs A and A combined and drugs B and B combined by using the Combo method, described in this paper, which provides (i) a flexible choice of interaction models and (ii) the use of nonparametric statistical methods. Synergistic effects against R5-HIV-1Ba-L and a 50:50 mixture of R5-HIV-1Ba-L and X4-HIV-1ERS104pre (HIV-1Ba-L/104pre) were seen when AVC was combined with zidovudine, nevirapine, indinavir, or enfuvirtide. Mild synergism and additivity were observed when AVC was combined with TAK779 and SCH-C, respectively. We also observed more potent synergism against HIV-1Ba-L/104pre when AVC was combined with AMD3100 or TE14011. The data demonstrate a tendency toward greater synergism with AVC plus either of the two CXCR4 inhibitors compared to the synergism obtained with combinations of AVC and other drugs, suggesting that the development of effective CXCR4 inhibitors may be important for increasing the efficacies of CCR5 inhibitors.

scholarly journals Fullerene Derivatives of Nucleoside HIV Reverse Transcriptase Inhibitors—In Silico Activity Prediction

2018 ◽  
Vol 19 (10) ◽  
pp. 3231 ◽  
Author(s):  
Aleksandra Dąbrowska ◽  
Tomasz Pieńko ◽  
Przemysław Taciak ◽  
Katarzyna Wiktorska ◽  
Zdzisław Chilmonczyk ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Hiv Reverse Transcriptase ◽  
Reverse Transcriptase Inhibitors ◽  
Activity Prediction ◽  
Hiv Therapy ◽  
C20 Fullerene ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Similar Affinity ◽  
Hiv 1

Here we present new derivatives of nucleoside reverse transcriptase inhibitors with a C20 fullerene. The computational chemistry methods used in this study evaluate affinity of designed compounds towards the HIV-1 reverse transcriptase (RT) binding site and select the most active ones. The best of the designed compounds have superior or similar affinity to RT active site in comparison to most active test compounds, including drugs used in anti-HIV therapy.

Lack of synergy in the inhibition of HIV-1 reverse transcriptase by combinations of the 5′-triphosphates of various anti-HIV nucleoside analogs

1993 ◽  
Vol 22 (4) ◽  
pp. 295-308 ◽  
Author(s):  
E.Lucile White ◽  
William B. Parker ◽  
Larry J. Ross ◽  
William M. Shannon
Keyword(s):  
Reverse Transcriptase ◽  
Nucleoside Analogs ◽  
Anti Hiv ◽  
Hiv 1
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