African derived phytocompounds may interfere with SARS-CoV-2 RNA capping machinery via inhibition of 2′-O-ribose methyltransferase: An in silico perspective

Gyebi, Gideon A.; Ogunyemi, Oludare M.; Adefolalu, Adedotun A.; Rodriguez-Martínez, Alejandro; López-Pastor, Juan F.; Banegas-Luna, Antonio Jesús; Pérez‐Sánchez, Horacio; Adegunloye, Adegbenro P.; Ogunro, Olalekan Bukunmi; Afolabi, Saheed O.

doi:10.1016/j.molstruc.2022.133019

Cited by 11 publications

(5 citation statements)

References 72 publications

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“…By examining the SASA (Solvent-Accessible Surface Area) of the compound within the protein binding region, we observe a range between 370 Å and 390 Å. A reduction in MolSA implies a compacting effect, surface burial, or the closure of pockets (Gyebi et al, 2022). Conversely, a signi cant increase in MolSA may indicate structural expansion, surface exposure, or the opening of cavities or binding sites.…”

Section: Discussionmentioning

confidence: 93%

Computational Discovery of Potent Imidazole Derivatives as Inhibitors of SARS-CoV-2 Main Protease: An Integrated Approach Combining Molecular Dynamics and Binding Affinity Analysis

Babalola,

Adegboyega

2023

Preprint

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One of the most pressing challenges associated with SARS treatment is the emergence of new variants that may be transmissible, causing more severe disease or being resistant to the current standard of treatment. This study aimed to identify potential drug candidates from newly synthesized imidazole derivatives against SARS-CoV-2 Main Protease (Mpro), a crucial drug target for treating viral infection, using a computational approach that integrated molecular docking and dynamics simulation. In this study, we utilized AutoDock Vina within the PyRx workspace for molecular docking analysis to explore the inhibitory effects of the compounds on the Mpro, a drug target for SARS-CoV-2. The ADMET properties of these compounds, including absorption, distribution, metabolism, excretion, and toxicity, were evaluated using the SwissADME and ADMETLab servers. Every one of the 18 compounds that were tested demonstrated strong binding affinities towards Mpro, with Imidazolyl-methanone C10 showing the most significant binding affinity. Moreover, pyridyl imidazole C5, thiophenyl-imidazole C1, and quinoline imidazole C14 displayed binding affinities of -8.3, -8.2, and -7.7 Kcal/mol, respectively. These compounds interacted with specific amino acid residues (HIS A:41 - CYS A:145) within the Mpro protein. To assess the stability of the ligand with the best binding affinity, molecular dynamics (MD) simulations were conducted using Schrodinger software, which revealed its stability over the simulation period. The study provides valuable insights into the potential of imidazole derivatives as SARS-CoV-2 Mpro inhibitors. All compounds including C10 display promising characteristics and hold potential as a drug candidate for SARS-CoV-2. However, further optimization and experimental validation of these compounds are necessary to advance their development as effective therapeutics against viral infections.

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Section: Discussionmentioning

confidence: 93%

Computational Discovery of Potent Imidazole Derivatives as Inhibitors of SARS-CoV-2 Main Protease: An Integrated Approach Combining Molecular Dynamics and Binding Affinity Analysis

Babalola,

Adegboyega

2023

Preprint

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“…By examining the SASA (solvent-accessible surface area) of the compound within the protein binding region, we observe a range from 370 Å to 390 Å. A reduction in MolSA implies a compacting effect, surface burial, or the closure of pockets [40]. Conversely, a significant increase in MolSA may indicate structural expansion, surface exposure, or the opening of cavities or binding sites.…”

Section: Discussionmentioning

confidence: 94%

Computational Discovery of Novel Imidazole Derivatives as Inhibitors of SARS-CoV-2 Main Protease: An Integrated Approach Combining Molecular Dynamics and Binding Affinity Analysis

Babalola,

Adegboyega

2024

COVID

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One of the most pressing challenges associated with SARS treatment is the emergence of new variants that may be transmissible, causing more severe disease or being resistant to the current standard of treatment. This study aimed to identify potential drug candidates from novel imidazole derivatives against SARS-CoV-2 main protease (Mpro), a crucial drug target for treating viral infection, using a computational approach that integrated molecular docking and dynamics simulation. In this study, we utilized AutoDock Vina within the PyRx workspace for molecular docking analysis to explore the inhibitory effects of the compounds on the Mpro, a drug target for SARS-CoV-2. The ADMET properties of these compounds, including absorption, distribution, metabolism, excretion, and toxicity, were evaluated using the SwissADME and ADMETLab servers. Each of the 18 compounds that were tested demonstrated strong binding affinities towards Mpro, with imidazolyl–methanone C10 showing the most significant binding affinity. Moreover, pyridyl–imidazole C5, thiophenyl–imidazole C1, and quinoline–imidazole C14 displayed binding affinities of −8.3, −8.2, and −7.7 Kcal/mol, respectively. These compounds interacted with specific amino acid residues (HIS A:41—CYS A:145) within the Mpro protein. To assess the stability of the ligand with the best binding affinity, molecular dynamics (MD) simulations were conducted using Schrodinger software, which revealed its stability over the simulation period. The study provides valuable insights into the potential of imidazole derivatives as SARS-CoV-2 Mpro inhibitors. All compounds including C10 display promising characteristics and hold potential as drug candidates for SARS-CoV-2. However, further optimization and experimental validation of these compounds are necessary to advance their development as effective therapeutics against viral infections.

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“…The lead bioactive flavonoids did not cause the protein's structural conformation to change; instead, a more compact structure was created, as seen by the flexibility of the amino acid residues of the protein targets that were accessible using the RMSF plots. 53,54 When comparing the lead bioactive flavonoid–bound complexes to the unbound protein, the close mean values for the different thermodynamic parameters show that the structural integrity of the enzymes was not compromised by bioactive flavonoid binding, 53,55 allowing for additional research on the complexes.…”

Section: Discussionmentioning

confidence: 99%

Exploring beetroot (Beta vulgaris L.) for diabetes mellitus and Alzheimer's disease dual therapy: in vitro and computational studies

Ojo,

Gyebi,

Ezenabor

et al. 2024

RSC Adv.

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African derived phytocompounds may interfere with SARS-CoV-2 RNA capping machinery via inhibition of 2′-O-ribose methyltransferase: An in silico perspective

Cited by 11 publications

References 72 publications

Computational Discovery of Potent Imidazole Derivatives as Inhibitors of SARS-CoV-2 Main Protease: An Integrated Approach Combining Molecular Dynamics and Binding Affinity Analysis

Computational Discovery of Potent Imidazole Derivatives as Inhibitors of SARS-CoV-2 Main Protease: An Integrated Approach Combining Molecular Dynamics and Binding Affinity Analysis

Computational Discovery of Novel Imidazole Derivatives as Inhibitors of SARS-CoV-2 Main Protease: An Integrated Approach Combining Molecular Dynamics and Binding Affinity Analysis

Exploring beetroot (Beta vulgaris L.) for diabetes mellitus and Alzheimer's disease dual therapy: in vitro and computational studies

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