Structure-based drug design of novel peptidomimetic cellulose derivatives as HCV-NS3 protease inhibitors

Saleh, Noha A.; Elshemey, Wael M.

doi:10.1016/j.lfs.2017.08.021

Cited by 13 publications

(18 citation statements)

References 51 publications

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“…The previous study in 2017 had suggested dimer cellulose attached to natural substrate (Glu-Asp-Val-Val-Cys-Cys) at position 6 as a promising HCV NS3 protease inhibitor ( Fig.1) [24]. In this study, some potent modifications are introduced to this promising inhibitors (parent compound).…”

Section: Resultsmentioning

confidence: 95%

“…The best scores docking systems are re-optimized via MM3 method to calculate the binding free energy. The binding energy is calculated according to the following equation [24]:…”

Section: The Biological Activitymentioning

confidence: 99%

“…The hexa-peptide sequences is the NS5A/NS5B junction for the Egyptian genotype 4 (Glu-Asp-Val-Val-Cys-Cys) consequently, it represents a natural substrate [41,42]. According to this study, the compound with hexa-peptide sequences attached to dimmer cellulose at position 6 has good inhibition activity against HCV NS3 protease [24].…”

Section: Introductionmentioning

confidence: 97%

“…One of the essential applications of CADD is the development of inhibitorssuch as anti-hepatitis C virus [18][19][20][21][22][23][24][25][26][27]. Hepatitis C virus (HCV) is a third type of hepatitis virus discovered after hepatitis A and B in 1970.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, structure-based drug design is performed to study the inhibition activity of novel compounds such as HCV NS3 protease inhibitors [24]. These inhibitors consist of dimmer cellulose and hexa-peptide sequences at different positions on cellulose.…”

Section: Introductionmentioning

confidence: 99%

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Physical properties and biological activity of some novel HCV NS3 protease inhibitors

Saleh

2018

Egypt. J. Physics

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T HEORETICAL molecular modelling mimics the physical, chemical and biological properties and the behavior of molecules using classical and quantum theoretical methods. Egypt is considered the most infected region in the world with hepatitis C virus (HCV) especially genotype 4a. The most important target enzyme for HCV inhibition is nonstructural 3 protease (NS3). Based on recent theoretical study, a possible potent inhibitor is a dimer cellulose with hexapeptide at position 6. In the present study, the physical properties and biological activity of suggested novel NS3 protease inhibitors for Egyptian genotype 4 are calculated using Parametrization method 3(PM3). These inhibitors are divided into two series. The first series is the dimer cellulose with hexapeptide modifications usingβ-amino acids, mix of α-and β-amino acids, α-ketoacids or phenyl acyl sulfonamide. The second series consists of a monomer cellulose instead of dimer cellulose with the same modifications in the hexapeptide sequences. Results show that, the two compounds with α-ketoacids in the first and second series have better physical properties as well as nearly similar biological activity compared to the recently studied inhibitor without any modifications.

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Section: Resultsmentioning

confidence: 95%

“…The best scores docking systems are re-optimized via MM3 method to calculate the binding free energy. The binding energy is calculated according to the following equation [24]:…”

Section: The Biological Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Physical properties and biological activity of some novel HCV NS3 protease inhibitors

Saleh

2018

Egypt. J. Physics

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Review on chemogenomic approaches towards hepatitis C viral targets

Venkatesan

2019

J of Cellular Biochemistry

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Hepatitis C virus (HCV) is the most prevalent viral pathogen that infects more than 185 million people worldwide. HCV infection leads to chronic liver diseases such as liver cirrhosis and hepatocellular carcinoma. Direct-acting antivirals (DAAs) are the recent combination therapy for HCV infection with reduced side effects than prior therapies. Sustained virological response (SVR) acts as a gold standard marker to monitor the success of antiviral treatment.Older treatment therapies attain 50-55% of SVR compared with DAAs which attain around 90-95%. The current review emphasizes the recent chemogenomic updates that have been unfolded through structure-based drug design of HCV drug target proteins (NS3/4A, NS5A, and NS5B) and ligand-based drug design of DAAs in achieving a stable HCV viral treatment strategies.

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In-silico study: docking simulation and molecular dynamics of peptidomimetic fullerene-based derivatives against SARS-CoV-2 Mpro

Saleh

2023

3 Biotech

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COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, has become a global pandemic resulting in significant morbidity and mortality. This study presents 12 new peptidomimetic fullerene-based derivatives in three groups that are investigated theoretically as SARS-CoV-2 M pro inhibitors to increase the chance of treating COVID-19. Studied compounds are designed and optimized at B88-LYP/DZVP method. Molecular descriptors results show the stability and reactivity of the compounds with M pro , especially in the 3rd group (Ser compounds). However, Lipinski's Rule of Five values indicates that the compounds are not suitable as oral drugs. Furthermore, molecular docking simulations are carried out to investigate the binding affinity and interaction modes of the top five compounds (compounds 1, 9, 11, 2, and 10) with the M pro protein, which have the lowest binding energy. Molecular dynamics simulations are also performed to evaluate the stability of the protein–ligand complexes with compounds 1 and 9 and compare them with natural substrate interaction. The analysis of RMSD, H-bonds, Rg, and SASA indicates that both compounds 1 (Gly-α acid) and 9 (Ser-α acid) have good stability and strong binding affinity with the M pro protein. However, compound 9 shows slightly better stability and binding affinity compared to compound 1.

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Structure-based drug design of novel peptidomimetic cellulose derivatives as HCV-NS3 protease inhibitors

Cited by 13 publications

References 51 publications

Physical properties and biological activity of some novel HCV NS3 protease inhibitors

Physical properties and biological activity of some novel HCV NS3 protease inhibitors

Review on chemogenomic approaches towards hepatitis C viral targets

In-silico study: docking simulation and molecular dynamics of peptidomimetic fullerene-based derivatives against SARS-CoV-2 Mpro

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