<i>In silico</i> identification of potential SARS COV-2 2′-<i>O</i>-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations

Hassab, Mahmoud A. El; Ibrahim, Tamer M.; Shoun, Aly A.; Al-Rashood, Sara T.; Alkahtani, Hamad M.; Alharbi, Amal; Eskandrani, Razan O.; Eldehna, Wagdy M.

doi:10.1039/d1ra01809d

Cited by 17 publications

(12 citation statements)

References 53 publications

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“…The free EGFR enzyme and the retrieved docking coordinates of the same enzyme bound Erlotinib, 9k and 9g were used as input structures for the molecular dynamics. The typical work scheme of Gromacs simulation was applied to conduct the four MDS 41 – 45 (Supplementary Materials).…”

Section: Methodsmentioning

confidence: 99%

Design, synthesis, in vitro biological assessment and molecular modeling insights for novel 3-(naphthalen-1-yl)-4,5-dihydropyrazoles as anticancer agents with potential EGFR inhibitory activity

Eldehna

Hassab

Elsayed

et al. 2022

Sci Rep

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Currently, the humanity is in a fierce battle against various health-related challenges especially those associated with human malignancies. This created the urge to develop potent and selective inhibitors for tumor cells through targeting specific oncogenic proteins possessing crucial roles in cancer progression and survive. In this respect, new series of pyrazole-thiazol-4-one hybrids (9a–p) were synthesized as potential anticancer agents. All the synthesized molecules exhibited potent antiproliferative actions against breast cancer (BC) T-47D and MDA-MB-231 cell lines with IC50 ranges 3.14–4.92 and 0.62–58.01, respectively. Moreover, the most potent anti-proliferative counterparts 9g and 9k were assessed against EGFR. They displayed nanomolar inhibitory activity, IC50 267 ± 12 and 395 ± 17 nM, respectively. Worth noting, both compounds 9g and 9k induced apoptosis in MDA-MB-231 cells, and resulted in a cell cycle arrest at G2/M phase. Furthermore, an in silico analysis including docking and molecular dynamic simulations was performed.

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Section: Methodsmentioning

confidence: 99%

Design, synthesis, in vitro biological assessment and molecular modeling insights for novel 3-(naphthalen-1-yl)-4,5-dihydropyrazoles as anticancer agents with potential EGFR inhibitory activity

Eldehna

Hassab

Elsayed

et al. 2022

Sci Rep

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“…Later on, complex topology was generated through joining both ligand and enzymes. As already published in the literature, the typical scheme for enzyme-ligand simulations by GROMACS was applied, starting with system solvation using a single point charge (SPC) water model and ending with neutralization by adding the suitable number of counter ions (El Hassab et al 2020, 2021, 2022a, 2022b.…”

Section: Molecular Dynamicsmentioning

confidence: 99%

Phytochemical Investigation of Egyptian Spinach Leaves, a Potential Source for Antileukemic Metabolites: In Vitro and In Silico Study

Abdelgawad

Hetta

Ibrahim

et al. 2022

Rev. Bras. Farmacogn.

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Spinacia oleracea L., Amaranthaceae, leaves cultivated in Egypt demonstrated a potential antileukemic activity against the chronic myeloid leukemia, K562 cell line. Thus, the aim of this study is to carry out a phytochemical investigation of S. oleracea leaves as well as the isolation of its antileukemic phytoconstituents. Phytochemical investigation of S. oleracea leaves resulted in the isolation of seventeen known compounds. The biological study revealed that compounds hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a remarkable antiproliferative activity against K562 cells in vitro. A mechanistic in silico study showed that hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a strong binding affinity towards topoisomerase (docking score −12.50, −9.19, and −13.29 kcal/mol, respectively), and showed as well a strong binding affinity towards Abl kinase (docking score −11.91, −9.35, and −12.59 kcal/mol, respectively). Molecular dynamics study revealed that 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid produced stable complexes with both topoisomerase and Abl kinase with RMSD values of 1.81 and 1.85 Å, respectively. As a result of our findings, we recommend more in vivo and preclinical studies to confirm the potential benefit of spinach leaves for chronic myeloid leukemia patients. Graphical Abstract

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“…In the repurposing against nsp16 involving 4200 drugs or compounds, the best one predicted from MM-PBSA was Carba-nicotinamide-adenine-dinucleotide . The potency of hundreds of bioactive compounds to methyltransferase was also studied via docking and MM/PBSA calculations. , Moreover, El Hassab et al designed a new methyltransferase inhibitor AP-20 based on fragments and calculated the binding affinity using MM/PBSA. Since the MMLFA-1/SARS-CoV-2 Orf7a complex contributes to SARS-CoV-2 infectivity and pathogenicity, Ongaro et al used MM/GBSA calculations to study the interactions inside the MMLFA-1/SARS-CoV-2 Orf7a complex.…”

Section: Methods and Approachesmentioning

confidence: 99%

“…In the work of searching COVID-19 therapeutics, most pharmacophore models focused on Mpro. ,,,,− Pharmacophore models were used to screen inhibitor compounds to SARS-CoV-2 from FDA-approved drugs, , DrugBank, or HIV inhibitors. , A fragment-based pharmacophore model was built from 22 noncovalent fragments cocrystallized with Mpro . More pharmacophore models were created for Mpro, − PLpro, and nsp16 …”

Section: Methods and Approachesmentioning

confidence: 99%

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Gao¹,

Wang²,

Chen³

et al. 2022

Chem. Rev.

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Despite tremendous efforts in the past two years, our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus–host interactions, immune response, virulence, transmission, and evolution is still very limited. This limitation calls for further in-depth investigation. Computational studies have become an indispensable component in combating coronavirus disease 2019 (COVID-19) due to their low cost, their efficiency, and the fact that they are free from safety and ethical constraints. Additionally, the mechanism that governs the global evolution and transmission of SARS-CoV-2 cannot be revealed from individual experiments and was discovered by integrating genotyping of massive viral sequences, biophysical modeling of protein–protein interactions, deep mutational data, deep learning, and advanced mathematics. There exists a tsunami of literature on the molecular modeling, simulations, and predictions of SARS-CoV-2 and related developments of drugs, vaccines, antibodies, and diagnostics. To provide readers with a quick update about this literature, we present a comprehensive and systematic methodology-centered review. Aspects such as molecular biophysics, bioinformatics, cheminformatics, machine learning, and mathematics are discussed. This review will be beneficial to researchers who are looking for ways to contribute to SARS-CoV-2 studies and those who are interested in the status of the field.

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In silico identification of potential SARS COV-2 2′-O-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations

Abstract: The identification of AP-20 as a potential SARS COV-2 2′-O-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations.

Cited by 17 publications

References 53 publications

Design, synthesis, in vitro biological assessment and molecular modeling insights for novel 3-(naphthalen-1-yl)-4,5-dihydropyrazoles as anticancer agents with potential EGFR inhibitory activity

Design, synthesis, in vitro biological assessment and molecular modeling insights for novel 3-(naphthalen-1-yl)-4,5-dihydropyrazoles as anticancer agents with potential EGFR inhibitory activity

Phytochemical Investigation of Egyptian Spinach Leaves, a Potential Source for Antileukemic Metabolites: In Vitro and In Silico Study

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

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