scholarly journals Bioisosteric Replacement as a Tool in Anti-HIV Drug Design

2020 ◽  
Vol 13 (3) ◽  
pp. 36 ◽  
Author(s):  
Alexej Dick ◽  
Simon Cocklin
Keyword(s):  
Drug Design ◽  
Chemical Space ◽  
Experimental Therapeutics ◽  
Scaffold Hopping ◽  
Bioisosteric Replacement ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Hiv 1

Bioisosteric replacement is a powerful tool for modulating the drug-like properties, toxicity, and chemical space of experimental therapeutics. In this review, we focus on selected cases where bioisosteric replacement and scaffold hopping have been used in the development of new anti-HIV-1 therapeutics. Moreover, we cover field-based, computational methodologies for bioisosteric replacement, using studies from our group as an example. It is our hope that this review will serve to highlight the utility and potential of bioisosteric replacement in the continuing search for new and improved anti-HIV drugs.

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.

Model of full-length HIV-1 integrase complexed with viral DNA as template for anti-HIV drug design

2004 ◽  
Vol 18 (12) ◽  
pp. 739-760 ◽  
Author(s):  
Rajeshri G. Karki ◽  
Yun Tang ◽  
Terrence R. Burke ◽  
Marc C. Nicklaus
Keyword(s):  
Drug Design ◽  
Full Length ◽  
Viral Dna ◽  
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.

scholarly journals Molecular dynamics for structural complexes of potential HIV-1 inhibitors with the viral envelope gp120 protein

2018 ◽  
Vol 62 (5) ◽  
pp. 576-584
Author(s):  
I. A. Kashyn ◽  
G. I. Nikolaev ◽  
M. A. Tuzikov ◽  
A. M. Andrianov
Keyword(s):  
Molecular Dynamics ◽  
Viral Envelope ◽  
Amino Acid Residues ◽  
Free Energies ◽  
Gp120 Protein ◽  
Dynamics Simulations ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Envelope Gp120

Molecular dynamics simulations for the structural complexes of potential HIV-1 inhibitors with the viral envelope gp120 protein were carried out. Free energies of the formation of these supramolecular structures and contributions of individual amino-acid residues of gp120 to the enthalpy binding were calculated. The residues of gp120 critical for interactions with the ligands were identified. Based on the data obtained, five compounds promising for synthesis and testing for antiviral activity were selected. It is suggested that these compounds may be successfully used in the design of novel, potent and broad anti-HIV drugs.

scholarly journals Discovery, SAR study and ADME properties of methyl 4-amino-3-cyano-1-(2-benzyloxyphenyl)-1H-pyrazole-5-carboxylate as an HIV-1 replication inhibitor

2020 ◽  
Vol 11 (5) ◽  
pp. 577-582
Author(s):  
Jeanne Fichez ◽  
Cathia Soulie ◽  
Laurent Le Corre ◽  
Sophie Sayon ◽  
Stéphane Priet ◽  
...  
Keyword(s):  
Viral Resistance ◽  
Adme Properties ◽  
Replication Inhibitor ◽  
Hiv Drugs ◽  
Sar Study ◽  
Anti Hiv ◽  
Hiv 1

Identified as an HIV-1 inhibitor in cellulo, this pyrazole does not belong to the three main classes of anti HIV-drugs, a feature of prime interest in the context of viral resistance.

In Silico Investigation of a HIV-1 Vpr Inhibitor Binding Site: Potential for Virtual Screening and anti-HIV Drug Design

2014 ◽  
pp. n/a-n/a ◽  
Author(s):  
Sy Bing Choi ◽  
Yee Siew Choong ◽  
Akiko Saito ◽  
Habibah A. Wahab ◽  
Nazalan Najimudin ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Drug Design ◽  
Binding Site ◽  
In Silico ◽  
Inhibitor Binding ◽  
Anti Hiv ◽  
Hiv 1
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