QSAR Analysis and Molecular Docking Simulation of Suggested Peptidomimetic NS3 Protease Inhibitors

Mostafa, Hamdy I.A.; Elbialy, Nihal Saad; Ezat, Ahmed A.; Saleh, Noha A.; Ibrahim, Medhat

doi:10.2174/15734099113096660048

Cited by 12 publications

(8 citation statements)

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“…The use of mathematical models describing the effectiveness of a drug as a potent activator or inhibitor of specific enzyme has been given a growing attention for drug design in the last decade. Structurespecific properties that could be modeled using a mathematical equation is the key for fabrication of novel antiviral drugs for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) (Ibrahim et al, 2012;Mostafa et al, 2014;Saleh et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

IDX-184 is a superior HCV direct-acting antiviral drug: a QSAR study

Elfiky

Elshemey

2016

Med Chem Res

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Quantitative structure-activity relationship (QSAR) parameters are good indicators for the reactivity of direct-acting antiviral drugs. Since molecular structure is related to molecular function, careful selection of molecular substitutions will result in more drugs that are potent. In this work, QSAR parameters are selected in order to compare the four drugs used as nucleotide inhibitors (NIs) for non-structural 5B (NS5B) RNA-dependent RNA polymerase (RdRp) of hepatitis C virus (HCV). These drugs are: ribavirin (widely used over the last 20 years), sofosbuvir (approved on December 2013 by FDA), and finally IDX-184 and R7128 (phase IIb of clinical trial drugs). The nucleotide analogues uracil (U), guanine (G), and cytosine (C) from which these drugs are fabricated are also compared to that group of drugs. QSAR parameters suggested that the drug IDX-184 is the best among all of the studied NIs. It also shows that NIs are always more reactive than their parent nucleotide.

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Section: Introductionmentioning

confidence: 99%

IDX-184 is a superior HCV direct-acting antiviral drug: a QSAR study

Elfiky

Elshemey

2016

Med Chem Res

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“…and Gly27 (for second monomer of HIV protease) are selected as group. Performing genetic algorithm, FASTDOCK, and PMF scoring function [42][43][44] was used to fit the ligand into the selected HIV protease active site residues. The optimization is recalculated for docking systems at MM3 force field.…”

Section: Docking Calculationsmentioning

confidence: 99%

On the Molecular Modeling Analyses of Novel HIV-1 Protease Inhibitors Based on Modified Chitosan Dimer

Al-Fifi

Saleh

Elhaes

et al. 2015

International Journal of Spectroscopy

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The molecular modeling studies include quantitative structure activity relationship, IR spectra, and docking calculations, occurring for novel inhibitors based on chitosan dimer which were tried as HIV protease. The inhibitors were investigated with molecular modeling calculations at different level of theories. Each compound has phenol with hydroxymethylcarbonyl (HMC) group which added to chitosan in positions 2, 3, 2′, or 3′. The geometry of studied compounds is optimized with semiempirical PM3 method. Quantitative structure activity relationship (QSAR) properties of the suggested compounds are calculated at the same level of theory. Depending on QSAR calculations, the compounds with positions 2 and 2′ are less hydrophilic. The position 2′ compound makes good docking interaction into HIV protease active site. Calculated IR spectra indicate that the interaction through hydrogen bonding through the hydrogen of OH at positions 3 and 3′ gives rise to two OH bands one for chitosan and the other for phenol and HMC group. While at position 3′ CH band starts to appear.

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“…The development of inhibitors and antiviral drugs such as anti-hepatitis C virus is one of the serious applications [18][19][20][21][22][23][24][25][26][27]. One of the most common viruses in the world is hepatitis C virus (HCV).…”

Section: Introductionmentioning

confidence: 99%

The calculated binding energy of peptide-mimic inhibitors with some mutated HCV NS3 protease

Saleh

2019

Egypt. J. Physics

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H EPATITIS C virus is considered one of the worldwide viruses with very large percentage of infection in population. It is as an epidemic disease in Egypt. The introduced compounds (a and b) in this study were previously investigated and gave good binding affinity and good inhibition activity with wild-type HCV NS3 protease. In the present work, calculated molecular docking and binding energy calculations are performed to predict the inhibition activity of suggested compounds against some mutated HCV NS3 proteases. Compound a has hexa-peptide with α-ketoacids instead of the thiol group (SH) of cysteine residues attached to monomer cellulose at position 6 and compound b has hexa-peptide with α-ketoacids instead of the thiol group (SH) of cysteine residues attached to dimer cellulose at position 6. Based on the calculated binding energy and number of hydrogen bonds in docking interaction between the compounds and mutated NS3 protease,the inhibition activity of compounds a and b with NS3 protease mutations is more than that with wild-type NS3 protease. Especially withD168V NS3 protease mutation.The mutation in virus enzymes is one of the major obstacles in hepatitis C virus treatment.

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QSAR Analysis and Molecular Docking Simulation of Suggested Peptidomimetic NS3 Protease Inhibitors

Cited by 12 publications

References 0 publications

IDX-184 is a superior HCV direct-acting antiviral drug: a QSAR study

IDX-184 is a superior HCV direct-acting antiviral drug: a QSAR study

On the Molecular Modeling Analyses of Novel HIV-1 Protease Inhibitors Based on Modified Chitosan Dimer

The calculated binding energy of peptide-mimic inhibitors with some mutated HCV NS3 protease

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