A Computational Model for Docking of Noncompetitive Neuraminidase Inhibitors and Probing their Binding Interactions with Neuraminidase of Influenza Virus H5N1

The H1N1 pandemic in 2009 and the H5N1 outbreak in 2005 have shocked the world as millions of people were infected and hundreds of thousands died due to the infections by the influenza virus. Oseltamivir, the most common drug to block the viral life cycle by inhibiting neuraminidase (NA) enzyme, has been less effective in some resistant cases due to the virus mutation. Presently, the binding of 10 chalcone derivatives towards H5N1 and H1N1 NAs in the non-catalytic and catalytic sites was studied using molecular docking. The in silico study was also conducted for its drug-like likeness such as Lipinski Rule, mutagenicity, toxicity and pharmacokinetic profiles. The result demonstrates that two chalcones (1c and 2b) have the potential for future NA inhibitor development. Compound 1c inhibits H5N1 NA and H1N1 NA with IC50 of 27.63 µM and 28.11 µM, respectively, whereas compound 2b inhibits NAs with IC50 of 87.54 µM and 73.17 µM for H5N1 and H1N1, respectively. The in silico drug-like likeness prediction reveals that 1c is 62% better than 2b (58%) in meeting the criteria. The results suggested that 1c and 2b have potencies to be developed as non-competitive inhibitors of neuraminidase for the future development of anti-influenza drugs.

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“…Although the potency of such a compound was not as strong as the known drugs, it may overcome the drug i.e. H274Y for the N1 protein [22].…”

Section: Introductionmentioning

confidence: 95%

A study on catalytic and non-catalytic sites of H5N1 and H1N1 neuraminidase as the target for chalcone inhibitors

et al. 2021

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“…They found only the values of MMPBSA using the normal mode method were close to experimental values (Wright et al, 2014 ). Influenza was also an important research topic in antiviral compounds, with targets such as neuraminidase protein (Wang and Chen, 2014 ; Tran et al, 2015 ; Chintakrindi et al, 2016 ; Yang et al, 2016 ), non-structural proteins (Ai et al, 2014 ), H7N9 neuraminidase (Phanich et al, 2016 ), and the M2 proton channel (Homeyer et al, 2016 ). Other antiviral targets were also examined, such as RNA-dependent RNA polymerase (Yu et al, 2014 ; Wang J. H. et al, 2016 ), NS3/4A hepatitis C virus protease (Xue et al, 2014 ; Fu and Wei, 2015 ; Meeprasert et al, 2016 ), human furin (Omotuyi, 2015 ), and the capsomere of virus-like particles (Li Y. Y. et al, 2014 ).…”

Section: Applications Of Mmpbsamentioning

confidence: 99%

Recent Developments and Applications of the MMPBSA Method

Wang

Greene

Xiao

et al. 2018

Front. Mol. Biosci.

416

327

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The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach has been widely applied as an efficient and reliable free energy simulation method to model molecular recognition, such as for protein-ligand binding interactions. In this review, we focus on recent developments and applications of the MMPBSA method. The methodology review covers solvation terms, the entropy term, extensions to membrane proteins and high-speed screening, and new automation toolkits. Recent applications in various important biomedical and chemical fields are also reviewed. We conclude with a few future directions aimed at making MMPBSA a more robust and efficient method.

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“…228,229 Chalcones have also shown antiviral efficacy against various human viruses, including the herpes simplex virus (HSV), hepatitis viruses, HIV, influenza viruses, and human immunodeficiency virus (HIV). They have been demonstrated to suppress viral gene expression, lower viral load, and prevent viral replication such as MERS-CoV, 230 HIV, 10,[231][232][233] influenza virus, [234][235][236] herpes simplex virus (HSV), 237 dengue virus (DEN), 238 human rhinovirus (HRV) 239,240 and hepatitis C virus (HCV). [241][242][243] Several human viruses have been found to react with hydroxyl chalcone derivatives 3, 4, 6, 60, and 158-168, as shown in Fig.…”

Section: Organic and Biomolecular Chemistry Reviewmentioning

confidence: 99%

Synthesis, reactions and application of chalcones: a systematic review

2023

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A Computational Model for Docking of Noncompetitive Neuraminidase Inhibitors and Probing their Binding Interactions with Neuraminidase of Influenza Virus H5N1

Abstract: We conclude that non-competitive type of inhibition, as shown in this study, can serve as an effective method to block NA and evade the currently seen drug resistance.

Cited by 11 publications

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A study on catalytic and non-catalytic sites of H5N1 and H1N1 neuraminidase as the target for chalcone inhibitors

A study on catalytic and non-catalytic sites of H5N1 and H1N1 neuraminidase as the target for chalcone inhibitors

Recent Developments and Applications of the MMPBSA Method

Synthesis, reactions and application of chalcones: a systematic review

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