Structure-Based Virtual Screening, Docking, ADMET, Molecular Dynamics, and MM-PBSA Calculations for the Discovery of Potential Natural SARS-CoV-2 Helicase Inhibitors from the Traditional Chinese Medicine

Metwaly, Ahmed M.; Elwan, Alaa; El-Attar, Abdul-Aziz M.M.; Al-Rashood, Sara T.; Eissa, Ibrahim H.

doi:10.1155/2022/7270094

Cited by 13 publications

(7 citation statements)

References 112 publications

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“…Also, the exploration of 5956 traditional Chinese medicine to identify potential inhibitors for the SARS-CoV-2 helicase enzyme was conducted. 17 Viral helicases are a sort of enzyme that is responsible for the unpack of the duplex oligonucleotides (RNA or DNA) into their constituent single strands besides other significant functions in the replication process. 18 Consequently, the inhibition of that vital enzyme could be a crucial step in the fight against the target virus.…”

Section: Introductionmentioning

confidence: 99%

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Computer-aided drug discovery of natural antiviral metabolites as potential SARS-CoV-2 helicase inhibitors

Elkaeed,

Eissa,

Saleh

et al. 2024

Journal of Chemical Research

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In our quest to discover effective inhibitors against severe acute respiratory syndrome coronavirus 2 helicase, a diverse set of more than 300 naturally occurring antiviral metabolites was investigated. Employing advanced computational techniques, we initiated the selection process by analyzing and comparing the co-crystallized ligand (VXG) of the severe acute respiratory syndrome coronavirus 2 helicase protein (PDB ID: 5RMM) to identify compounds with structurally similar features and potential for comparable binding. Through structural similarity and pharmacophore research, 13 compounds that shared important characteristics with VXG were pinpointed. Subsequently, these candidates were subjected to molecular docking to identify seven compounds that demonstrated favorable energy profiles and accurate binding to the severe acute respiratory syndrome coronavirus 2 helicase. Among these, mycophenolic acid emerged as the most promising candidate. To ensure the safety and viability of the selected compounds, we conducted ADMET tests, which confirmed the favorable characteristics of mycophenolic acid, and the safety of atropine and plumbagin. Building on these results, we performed additional analyses on mycophenolic acid, including various molecular dynamics simulations. These investigations demonstrated that mycophenolic acid exhibited optimal binding to the severe acute respiratory syndrome coronavirus 2 helicase, maintaining flawless dynamics throughout the simulations. Furthermore, the Molecular Mechanics Poisson–Boltzmann Surface Area tests provided strong evidence that mycophenolic acid successfully formed a stable connection with the severe acute respiratory syndrome coronavirus 2 helicase, with a calculated free energy value of −294 kJ mol−1. These encouraging findings provide a solid foundation for further research, including in vitro and in vivo studies, on the three identified compounds. The potential efficacy of these compounds as treatment options for coronavirus-19 warrants further exploration and may hold significant promise in the ongoing fight against the pandemic.

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Section: Introductionmentioning

confidence: 99%

“…Also, the exploration of 5956 traditional Chinese medicine to identify potential inhibitors for the SARS-CoV-2 helicase enzyme was conducted. 17…”

Section: Introductionmentioning

confidence: 99%

Computer-aided drug discovery of natural antiviral metabolites as potential SARS-CoV-2 helicase inhibitors

Elkaeed,

Eissa,

Saleh

et al. 2024

Journal of Chemical Research

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“…Also, we conducted an exploration of a collection of 5956 compounds sourced from traditional Chinese medicine with the aim of identifying potential natural inhibitors for the SARS-CoV-2 helicase enzyme. 22 We herein report the structure and ligand-based in silico discovery of potential SARS-CoV-2 helicase inhibitors among 4924 natural African metabolites. The screened compounds were obtained from the African Natural Products Database, which was collected from various natural products databases of several African regions covering from 1962 to 2019.…”

Section: Introductionmentioning

confidence: 99%

Computer-Assisted Drug Discovery of Potential African Anti-SARS-CoV-2 Natural Products Targeting the Helicase Protein

Metwaly,

Alesawy,

Alsfouk

et al. 2024

Natural Product Communications

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Objectives: In our continuous efforts to combat COVID-19, our objective was to conduct a comprehensive computer-aided drug design study utilizing 4924 African natural metabolites sourced from diverse databases across various African regions from 1962 to 2019. The primary goal was to target the SARS-CoV-2 helicase, a crucial enzyme in viral replication. Methods: We employed structural fingerprint and molecular similarity studies with VXG, the co-crystallized ligand, as a reference. Subsequently, docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were conducted. Results: The structural fingerprint analysis identified 200 structurally similar compounds, then the molecular similarity studies selected 40 compounds. Among them, 15 metabolites with low free energies, favorable binding modes, and promising ADMET properties were identified. Four compounds were excluded according to the toxicity studies. Compound 1552, 1-(( S)-2,3-dihydro-2-(( R)-1-hydroxypropan-2-yl)benzofuran-5-yl)ethenone, exhibited the most favorable docking results. Molecular dynamics simulations conclusively demonstrated its stable binding to the SARS-CoV-2 helicase, characterized by low energy and optimal dynamics. Conclusion: The findings suggest promising avenues for potential COVID-19 cures, encouraging further exploration through in vitro and in vivo studies of the identified compounds, particularly compound 1552.

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“…29 Additionally, we explored a collection of 5956 compounds from traditional Chinese medicine to identify potential natural inhibitors for the SARS-CoV-2 Helicase. 30 Lastly, we discovered the most active semisynthetic inhibitor for the COVID-19 papain-like protease from a group of 69 molecules. 31 For this study, a curated set of 4924 African natural products was meticulously selected.…”

Section: Introductionmentioning

confidence: 99%

Computer-assisted drug discovery of potential natural inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase through a multi-phase in silico approach

Elkaeed,

Alsfouk,

Ibrahim

et al. 2023

Antiviral Therapy

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Background The COVID-19 pandemic has led to significant loss of life and economic disruption worldwide. Currently, there are limited effective treatments available for this disease. SARS-CoV-2 RNA-dependent RNA polymerase (SARS-CoV-2 RdRp) has been identified as a potential target for drug development against COVID-19. Natural products have been shown to possess antiviral properties, making them a promising source for developing drugs against SARS-CoV-2. Objectives The objective of this study is to identify the most effective natural inhibitors of SARS-CoV-2 RdRp among a set of 4924 African natural products using a multi-phase in silico approach. Methods The study utilized remdesivir (RTP), the co-crystallized ligand of RdRp, as a starting point to select compounds that have the most similar chemical structures among the examined set of compounds. Molecular fingerprints and structure similarity studies were carried out in the first part of the study. The second part of the study included molecular docking against SARS-CoV-2 RdRp (PDB ID: 7BV2) and Molecular Dynamics (MD) simulations including the calculation of RMSD, RMSF, Rg, SASA, hydrogen bonding, and PLIP. Moreover, the calculations of Molecular mechanics with generalised Born and surface area solvation (MM-GBSA) Lennard-Jones and Columbic electrostatic interaction energies have been conducted. Additionally, in silico ADMET and toxicity studies were performed to examine the drug likeness degrees of the selected compounds. Results Eight compounds were identified as the most effective natural inhibitors of SARS-CoV-2 RdRp. These compounds are kaempferol 3-galactoside, kaempferol 3- O- β-D-glucopyranoside, mangiferin methyl ether, luteolin 7- O- β-D-glucopyranoside, quercetin- O- β-D-3-glucopyranoside, 1-methoxy-3-indolylmethyl glucosinolate, naringenin, and asphodelin A 4’- O- β-D-glucopyranoside. Conclusion The results of this study provide valuable information for the development of natural product-based drugs against COVID-19. However, the elected compounds should be further studied in vitro and in vivo to confirm their efficacy in treating COVID-19.

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Structure-Based Virtual Screening, Docking, ADMET, Molecular Dynamics, and MM-PBSA Calculations for the Discovery of Potential Natural SARS-CoV-2 Helicase Inhibitors from the Traditional Chinese Medicine

Cited by 13 publications

References 112 publications

Computer-aided drug discovery of natural antiviral metabolites as potential SARS-CoV-2 helicase inhibitors

Computer-aided drug discovery of natural antiviral metabolites as potential SARS-CoV-2 helicase inhibitors

Computer-Assisted Drug Discovery of Potential African Anti-SARS-CoV-2 Natural Products Targeting the Helicase Protein

Computer-assisted drug discovery of potential natural inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase through a multi-phase in silico approach

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