In silico discovery of multi-targeting inhibitors for the COVID-19 treatment by molecular docking, molecular dynamics simulation studies, and ADMET predictions

Hasan, Aso Hameed; Hussen, Narmin Hamaamin; Shakya, Sonam; Jamalis, Joazaizulfazli; Pratama, Mohammad Rizki Fadhil; Chander, Subhash; Kharkwal, Harsha; Murugesan, Sankaranarayanan

doi:10.1007/s11224-022-01996-y

Cited by 21 publications

(9 citation statements)

References 94 publications

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“…MD simulations have been conducted in many previously published studies to investigate the validity of docked complexes ( Mahmud et al, 2021 ; Hasan et al, 2022 ). MD simulation is a strong biophysical technique that can uncover proper binding conformations and other vital dynamic values of ligand–protein interactions.…”

Section: Resultsmentioning

confidence: 99%

Therapeutic effects of Crataegus monogyna inhibitors against breast cancer

et al. 2023

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Breast cancer is a silent killer disorder among women and a serious economic burden in healthcare management. Every 19 s, a woman is diagnosed with breast cancer, and every 74 s, a woman worldwide passes away from the disease. Despite the increase in progressive research, advanced treatment approaches, and preventive measures, breast cancer rates continue to increase. This study provides a combination of data mining, network pharmacology, and docking analysis that surely could revolutionize cancer treatment by exploiting prestigious phytochemicals. Crataegus monogyna is a small, rounded deciduous tree with glossy, deeply lobed leaves and flat sprays of cream flowers, followed by dark red berries in autumn. Various studies demonstrated that C. monogyna is therapeutically effective against breast cancer. However, the particular molecular mechanism is still unknown. This study is credited for locating bioactive substances, metabolic pathways, and target genes for breast cancer treatment. According to the current investigation, which examined compound–target genes–pathway networks, it was found that the bioactive compounds of C. monogyna may operate as a viable solution against breast cancer by altering the target genes implicated in the disease pathogenesis. The expression level of target genes was analyzed using GSE36295 microarray data. Docking analysis and molecular dynamic simulation studies further strengthened the current findings by validating the effective activity of the bioactive compounds against putative target genes. In summary, we propose that six key compounds, luteolin, apigenin, quercetin, kaempferol, ursolic acid, and oleanolic acid, contributed to the development of breast cancer by affecting the MMP9 and PPARG proteins. Integration of network pharmacology and bioinformatics revealed C. monogyna’s multitarget pharmacological mechanisms against breast cancer. This study provides convincing evidence that C. monogyna might partially alleviate breast cancer and ultimately lays a foundation for further experimental research on the anti-breast cancer activity of C. monogyna.

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Section: Resultsmentioning

confidence: 99%

Therapeutic effects of Crataegus monogyna inhibitors against breast cancer

et al. 2023

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“…7 ). According to the literature, RMSD value of less than 3.0 Å is the most acceptable, as the lower the RMSD value shows greater stability of complex [140] , [141] . The obtained results indicated that Piscisoflavone C forms a more stable protein–ligand complex than Dioscin and does not make any considerable conformational change in the protein structure during simulation study.…”

Section: Discussionmentioning

confidence: 99%

Potential inhibitory activity of phytoconstituents against black fungus: In silico ADMET, molecular docking and MD simulation studies

Hussen¹,

Hasan²,

Jamalis³

et al. 2022

Computational Toxicology

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“…Vina software was run in exhaustiveness = 8. The binding site was selected based on its co-crystallized ligand (N3) with the target protein [ 33 ]. Affinity scores (in kcal/mol) given by AutoDock Vina for all the compounds were obtained and ranked based on the free energy binding theory (more negative value means greater binding affinity).…”

Section: Methodsmentioning

confidence: 99%

One-pot synthesis, molecular docking, ADMET, and DFT studies of novel pyrazolines as promising SARS-CoV-2 main protease inhibitors

et al. 2022

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Pyrazoline and its derivatives have numerous prominent pharmacological effects. Focusing on its anti-viral property, we have designed and synthesized three novel pyrazoline derivatives ( A1–A3 ) through one-pot three components and characterized them using different spectroscopic techniques (FT-IR, 1 H NMR, 13 C NMR, and UV). These compounds were evaluated against SARS-CoV-2 main protease utilizing in-silico molecular docking studies. The docking results displayed good inhibitory activity of the synthesized compounds. Among them, compound A2 was the most active against targeted protein. The drug-likeness and ADMET properties were predicted to have varied profiles but could still be developed, especially A2 . DFT/TD-DFT calculations through B3LYP/6-311G++ level of theory were applied to provide comparable theoretical data along with MEP map and electronic energy gap of HOMO → LUMO. Supplementary Information The online version contains supplementary material available at 10.1007/s11164-022-04831-5.

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In silico discovery of multi-targeting inhibitors for the COVID-19 treatment by molecular docking, molecular dynamics simulation studies, and ADMET predictions

Cited by 21 publications

References 94 publications

Therapeutic effects of Crataegus monogyna inhibitors against breast cancer

Therapeutic effects of Crataegus monogyna inhibitors against breast cancer

Potential inhibitory activity of phytoconstituents against black fungus: In silico ADMET, molecular docking and MD simulation studies

One-pot synthesis, molecular docking, ADMET, and DFT studies of novel pyrazolines as promising SARS-CoV-2 main protease inhibitors

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