<i>In silico</i> analysis of marine natural product from sponge (<i>Clathria</i> Sp.) for their activity as inhibitor of SARS-CoV-2 Main Protease

Ramadhan, Dwi Syah Fitra; Siharis, Fatmasari; Abdurrahman, Syawal; Isrul, Muhammad; Fakih, Taufik Muhammad

doi:10.1080/07391102.2021.1959405

Cited by 15 publications

(11 citation statements)

References 24 publications

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“…The appropriateness of these parameters was assessed via the root mean square deviation (RMSD) between the ligand molecule that scored highest postdocking and the co-crystallized ligand molecule. As a general rule, an RMSD of ≤ 2 Å [26] indicates a successful replication of the initial binding mode between ligand and receptor through the docking procedure, thereby affirming the reasonableness of the docking parameters.…”

Section: Re-docking Of Ligand Molecules With Receptor Targetsmentioning

confidence: 73%

In silico study to identify novel NEK7 inhibitors from natural source by a combination strategy

Zhang

Yao

et al. 2023

Preprint

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Cancer remains a significant health problem and stands as one of the primary causes of death worldwide. NEK7, a NIMA-related protein kinase, plays a crucial role in spindle assembly and cell division. Dysregulation of the NEK7 protein contributes to the development and progression of various malignancies, such as colon cancer and breast cancer. Therefore, the inhibition of NEK7 shows promise as a potential clinical target for anticancer therapy. Nevertheless, there is a dearth of high-quality NEK7 inhibitors. In this study, we utilized virtual screening, molecular docking, silicon-based pharmacokinetics, molecular dynamics (MD) simulations, and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA)-based binding free energy calculations to comprehensively analyze effective natural inhibitors that target NEK7 within the current framework. By employing molecular docking, including semi-flexible and flexible docking methods, we identified three natural products as hit compounds with binding modes similar to the active control dabrafenib. ADME/T predictions indicated that these hit molecules exhibited lower toxicity when administered orally. Additionally, through DFT calculations, we determined that the popular compound (-)-balanol possessed high chemical activity. Finally, 100 ns molecular dynamics simulations and energy decomposition revealed that the hit compounds displayed superior binding energy compared to the active control and demonstrated higher affinity. Based on the findings of our current research, we conclude that these newly discovered natural inhibitors may serve as parent structures for the development of more potent derivatives with promising biological activities. However, further experimental validation is necessary as part of subsequent investigations.

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Section: Re-docking Of Ligand Molecules With Receptor Targetsmentioning

confidence: 73%

In silico study to identify novel NEK7 inhibitors from natural source by a combination strategy

Zhang

Yao

et al. 2023

Preprint

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“…Nevertheless, first, the authors validated our setup docking protocol. As a result, the authors’ docking protocol passed an acceptance criterion (root-mean-square deviation, RMSD, <2), indicating a reliable docking result [ 21 , 22 ]. The validation result is in a supplementary file (Figures S4 and S5) .…”

Section: Resultsmentioning

confidence: 99%

“…The RMSD of the whole zebrafish MC1R plus α-MSH obtained from the docking server was calculated and compared to human MC1R protein bound with α-MSH, our template. The total RMSD value was less than 2 Å ( Figure S9C ), indicating an accepted range to consider as a precise prediction [ 21 , 22 ]. Therefore, the selected binding pocket on the zebrafish MC1R was later used for ligand–protein docking in the following steps.…”

Section: Resultsmentioning

confidence: 99%

“…Next, the authors extracted α-MSH from the original model obtained in the previous paragraph and re-docked it back to the binding pocket. As a result, the established docking parameters could imitate the original model with an RMSD value equal to 1.118 Å, Figure S10 [ 21 , 22 ]. Finally, the authors docked two more derivatives of each compound (six compounds in total, Figures S11 and S12 ), helping to identify the best docking pose of each molecule after superpositioning all obtained docking poses [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

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In Vitro, In Vivo, and In Silico Analyses of Molecular Anti-Pigmentation Mechanisms of Selected Thai Rejuvenating Remedy and Bioactive Metabolites

et al. 2023

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Thai rejuvenating remedies are mixed herbal formulas promoting longevity. Due to the complexity, the biological activities of these remedies are minimal. Therefore, in this study, the authors evaluated the anti-pigmentation effect at the molecular level of the selected Thai rejuvenating remedy to fulfill the knowledge gap. First, the authors found that the selected remedy showed promising activity against the tyrosinase enzyme with an IC50 value of 9.41 µg/mL. In the comparison, kojic acid (positive control) exhibited an IC50 value of 3.92 µg/mL against the same enzyme. Later, the authors identified glabridin as a bioactive molecule against tyrosinase with an IC50 value of 0.08 µg/mL. However, ethyl p-methoxycinnamate was the most abundant metabolite found in the remedy. The authors also found that the selected remedy and glabridin reduced the melanin content in the cell-based assay (B16F1) but not in the zebrafish larvae experiment. Finally, the authors conducted a computational investigation through molecular docking proposing a theoretical molecular interplay between glabridin, ethyl p-methoxycinnamate, and target proteins (tyrosinase and melanocortin-1 receptor, MC1R). Hence, in this study, the authors reported the molecular anti-pigmentation mechanism of the selected Thai rejuvenating remedy for the first time by combining the results from in silico, in vitro, and in vivo experiments.

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“…(marine sponge) natural compounds (Clathrin-A; -6.67 kcal/mol, Clathrin-B -7.09 kcal/mol, Clathsterol; -2.20 kcal/mol, and Mirabilin-G; -7.38 kcal/mol). Among these four compounds, Clathsterol showed four H-bond formations (CYS145, HIS163, THR26, GLY143) and Mirabilin-G showed one H-bond formation (GLU166) in Domain -I and Domain -II [36]. According to [37] the docking studies for 57 antiviral marine alkaloids with SARS-CoV-2 Main protease.…”

Section: Sars-cov-2 Mainmentioning

confidence: 99%

Screening and Druggability Analysis of Marine Active Metabolites against SARS-CoV-2: An Integrative Computational Approach

Murugesan¹,

Ragavendran²,

Almasi‐Hashiani³

et al. 2022

Preprint

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered a recent pandemic of respiratory disease and affected almost every country all over the world. A large amount of natural bioactive compounds is under clinical investigation for various diseas-es. Especially, marine natural compounds are gaining more attention in the new drug develop-ment process. The present study has aimed to identify potential marine-derived inhibitors against the target proteins of COVID-19 using a computational approach. Currently, 16 marine clinical-level compounds were selected for computational screening against the four SARS-CoV-2 main proteases. Computational screening resulted from the best drug candidates for each target based on the binding affinity scores and amino acid interactions. Among these, five marine-derived compounds namely Chrysophaentin A (-6.6 kcal/mol), Geodisterol sulfates (-6.6 kcal/mol), Hymenidin (-6.4 kcal/mol), Plinabulin (-6.4 kcal/mol) and Tetrodotoxin (-6.3 kcal/mol) expressed the minimized binding energy and molecular interactions such as covalent and hydrophobic interactions to the SARS CoV-2 Main Protease. Using Molecular dynamic stud-ies, the Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), Radius of Gyration (ROG), and Hydrogen bonds (H-Bonds) values were calculated for SARS-CoV-2 Main Protease with Hymenidin docked complex. Additionally, in silico Druglikeness and pharmaco-kinetic property assessments of the compounds demonstrated favorable druggability. These re-sults suggested that marine natural compounds are capable of fighting SARS-CoV-2. Further, in vitro and in vivo studies need to be carried out to confirm their inhibitory potential.

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In silico analysis of marine natural product from sponge (Clathria Sp.) for their activity as inhibitor of SARS-CoV-2 Main Protease

Cited by 15 publications

References 24 publications

In silico study to identify novel NEK7 inhibitors from natural source by a combination strategy

In silico study to identify novel NEK7 inhibitors from natural source by a combination strategy

In Vitro, In Vivo, and In Silico Analyses of Molecular Anti-Pigmentation Mechanisms of Selected Thai Rejuvenating Remedy and Bioactive Metabolites

Screening and Druggability Analysis of Marine Active Metabolites against SARS-CoV-2: An Integrative Computational Approach

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