Phytochemical analysis, molecular docking and molecular dynamics simulations of selected phytoconstituents from four herbs as anti-dotes for snake bites

Subasri, S.; Viswanathan, V.; Kesharwani, Manish; Velmurugan, D.

doi:10.15761/cpb.1000117

Cited by 8 publications

(5 citation statements)

References 18 publications

(19 reference statements)

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“…Analysis of the biomolecular interactions and the analysis of the interface between the arrangement and activity of proteins can aid in the development of new drugs, and the performance data from the dynamic trajectory analysis named the molecular dynamic simulation (MDS) [ 24 , 25 ] are used to analyze the stability and the intermolecular interactions of a protein-ligand complex in real-time. When a sophisticated system is subjected to an artificial environment, this technique can also be used to determine its conformational change.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Melongosides as Potential Inhibitors of NS2B-NS3 Activator-Protease of Dengue Virus (Serotype 2) by Using Molecular Docking and Dynamics Simulation Approach

Biswas¹,

Rumi

Khan³

et al. 2022

Journal of Tropical Medicine

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Dengue is a Flavivirus infection transmitted through mosquitoes of the Aedes genus, which is known to occur in over 100 countries of the world. Dengue has no available drugs for treatment; CYD-TDV is the only vaccine thus far approved for use by a few countries in the world. In the absence of drugs and a widely approved vaccine, attention has been focused on plant-derived compounds to the discovery of a potential therapeutic for DENV. The present study aimed to determine, in silico, the binding energies of the steroidal saponins, melongosides, to NS2B-NS3 activator protease of DENV-2, which plays an essential role in the viral replication. The blind molecular docking studies carried out gave binding energies (ΔG = −kcal/mol) of melongosides B, F, G, H, N, O, and P as 7.7, 8.2, 7.6, 7.8, 8.3, 8.0, and 8.0, respectively. All the melongosides interacted with the NS3 protease part of NS2B-NS3. Melongosides B, F, and N showed interactions with His51, while melongoside G interacted with Asp75 of NS3, to be noted, these are important amino acid residues in the catalytic site of the NS3 protease. However, the 200 ns molecular dynamic simulation experiment indicates significant stability of the protein-ligand interactions with the RMSD values of 2.5 Å, thus suggesting a better docking position and no disruption of the protein-ligand structure. Taken together, melongosides need further attention for more scientific studies as a DENV inhibitory agent, which if proven, in vivo and in clinical trials, can be a useful therapeutic agent against at least DENV-2.

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Section: Resultsmentioning

confidence: 99%

Evaluation of Melongosides as Potential Inhibitors of NS2B-NS3 Activator-Protease of Dengue Virus (Serotype 2) by Using Molecular Docking and Dynamics Simulation Approach

Biswas¹,

Rumi

Khan³

et al. 2022

Journal of Tropical Medicine

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“…Molecular docking is the process that estimates how two or more molecules bind together with the best structural confirmation and the lowest binding energy. The more significant and efficient drug candidates were selected based on the scoring value of molecular docking using the PyRx virtual screening tool [Version: 0.8] [ 44 , 45 ]. The docking operation for the five phytochemicals and control molecules with receptor SYK kinase found that the docking score of the control was −6.5 Kcal/mol.…”

Section: Discussionmentioning

confidence: 99%

“…Indispensable hydrogen bonds were also added to the macromolecules for more precise docking, and the total operation was conducted by the “UCSF Chimera package tool (Version-1.14)”, here must followed the “Gasteiger’s method” [ 44 ]. The prepared protein structures were saved in PDB format and conserved for further analysis [ 45 ].…”

Section: Methodsmentioning

confidence: 99%

Analysis of SYK Gene as a Prognostic Biomarker and Suggested Potential Bioactive Phytochemicals as an Alternative Therapeutic Option for Colorectal Cancer: An In-Silico Pharmaco-Informatics Investigation

Biswas¹,

Dey

Rahman

et al. 2021

JPM

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Background: SYK gene regulates the expression of SYK kinase (Spleen tyrosine kinase), an important non-receptor protein-tyrosine kinase for immunological receptor-mediated signaling, which is also considered a tumor growth metastasis initiator. An onco-informatics analysis was adopted to evaluate the expression and prognostic value of the SYK gene in colorectal cancer (CRC), the third most fatal cancer type; of late, it may be a biomarker as another targeted site for CRC. In addition, identify the potential phytochemicals that may inhibit the overexpression of the SYK kinase protein and minimize the human CRC. Materials & Methods: The differential expression of the SYK gene was analyzed using several transcriptomic databases, including Oncomine, UALCAN, GENT2, and GEPIA2. The server cBioPortal was used to analyze the mutations and copy number alterations, whereas GENT2, Gene Expression Profiling Interactive Analysis (GEPIA), Onco-Lnc, and PrognoScan were used to examine the survival rate. The protein-protein interaction network of SYK kinase and its co-expressed genes was conducted via Gene-MANIA. Considering the SYK kinase may be the targeted site, the selected phytochemicals were assessed by molecular docking using PyRx 0.8 packages. Molecular interactions were also observed by following the Ligplot+ version 2.2. YASARA molecular dynamics simulator was applied for the post-validation of the selected phytochemicals. Results: Our result reveals an increased level of mRNA expression of the SYK gene in colorectal adenocarcinoma (COAD) samples compared to those in normal tissues. A significant methylation level and various genetic alterations recurrence of the SYK gene were analyzed where the fluctuation of the SYK alteration frequency was detected across different CRC studies. As a result, a lower level of SYK expression was related to higher chances of survival. This was evidenced by multiple bioinformatics platforms and web resources, which demonstrated that the SYK gene can be a potential biomarker for CRC. In this study, aromatic phytochemicals, such as kaempferol and glabridin that target the macromolecule (SYK kinase), showed higher stability than the controls, and we have estimated that these bioactive potential phytochemicals might be a useful option for CRC patients after the clinical trial. Conclusions: Our onco-informatics investigation suggests that the SYK gene can be a potential prognostic biomarker of CRC. On the contrary, SYK kinase would be a major target, and all selected compounds were validated against the protein using in-silico drug design approaches. Here, more in vitro and in vivo analysis is required for targeting SYK protein in CRC.

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“…All the interacted twenty genes are directly or indirectly connected with different cancer. HCLS1 contains the potential prognostic characteristics with CRC [67], Lyn can be used as a prime target for the treatment of hormone-refractory human prostate cancer (PC), and Lyn is also involved in the activation of CRC [68,69], PTEN was identified as a tumor suppressor and a therapeutic target for cancer [70], WIPF1 is a candidate of the breast, brain, and colorectal cancer prognosis [71], as an ErbB subfamily, the ErbB4 gene plays a significant role in breast carcinogenesis with breast cancer prognostics and therapy [72], CBL-b can regulate cancer metastasis [73], EPOR contributes to breast cancer progression [74], CTTN can be used as new molecular therapeutic targets for Esophageal squamous cell carcinoma (ESCC) and CTTN also promotes the proliferation of CRC cells [75,76] and so on. Here, these 2 categories of protein-protein interaction networks depicted that SYK has interacted with those genes that are somehow involved in tumor suppression or tumor promotion.…”

Section: Discussionmentioning

confidence: 99%

“…2.7 Extracting lead molecule for Optimization Phytochemicals were first retrieved from the PubChem data base to prepare the Ligand for the docking of protein-ligands and obtained the 3D phytochemical structure required for molecular docking. The compounds were prepared as a ligand by using UCSF Chimera 1.14 (https://www.cgl.ucsf.edu/chimera/) tool, where optimization of ligand, added hydrogen atoms, charges at zero, and the output file saves as PDB format [40].…”

Section: Correlation Analysis and Interaction Networkmentioning

confidence: 99%

Evaluation of SYK Gene as a Prognostic Biomarker and Suggested Aromatic Potential Phytochemicals to Halt the Colorectal Cancer

Biswas¹,

Dey²,

Rahman³

et al. 2021

Preprint

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Background: Colorectal cancer is considered the third most fetal among all type of cancer. Spleen tyrosine kinase (SYK) is a non-receptor type tyrosine-protein that plays crucial role in signaling mediated via immune receptor. We adopted an onco-informatics analysis to evaluate the SYK expression and prognostic value of SYK in colorectal cancer, and identification of potential phytochemicals which may inhibit overexpression of SYK protein as well as minimized colorectal cancer. Materials & Methods: Differential expression of SYK gene was analyzed using the several transcriptomic databases including Oncomine, UALCAN, GENT2 and GEPIA2. The server, cBioPortal was used to analyze mutation and copy number alterations whereas GENT2, GEPIA, OncoLnc and PrognoScan were employed to examine the survival rate. A protein-protein interaction network of SYK and co-expressed genes of SYK was conducted via GeneMANIA. Considering SYK gene encoding protein as drug target, selected phytochemicals were assessed by molecular docking using PyRx 0.8 packages. YASARA molecular dynamics simulators were applied for the post validation of the molecular docking data. Results: We have observed significant overexpression of mRNA expression levels of SYK gene colorectal adenocarcinoma (COAD) samples compared with normal tissues. Significant methylation level and various genetic alterations are assembled in SYK gene which can lead to the development of colorectal cancer. As a result, lower level of SYK expression was related to the more chances of patients’ survival by which all the outcomes from the multiple bioinformatics platforms and web resources have demonstrated the significant evidences that the SYK kinsase can possess as a potential biomarker for the treatment of colorectal cancer. Here, aromatic phytochemicals namely, Kaempferol and Glabridin targeting SYK showed more stability compared to controls and may be useful for the treatment of colorectal cancer. Conclusion: Our study showed dysregulated expression of SYK in colorectal cancer and potentiality to act as a biomarker for the prognosis of CRC. Moreover, we have shown phytochemicals (Kaempferol and Glabridin) target SYK as potential treatment strategies and drug repositioning potentiality in colorectal cancer.

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Phytochemical analysis, molecular docking and molecular dynamics simulations of selected phytoconstituents from four herbs as anti-dotes for snake bites

Cited by 8 publications

References 18 publications

Evaluation of Melongosides as Potential Inhibitors of NS2B-NS3 Activator-Protease of Dengue Virus (Serotype 2) by Using Molecular Docking and Dynamics Simulation Approach

Evaluation of Melongosides as Potential Inhibitors of NS2B-NS3 Activator-Protease of Dengue Virus (Serotype 2) by Using Molecular Docking and Dynamics Simulation Approach

Analysis of SYK Gene as a Prognostic Biomarker and Suggested Potential Bioactive Phytochemicals as an Alternative Therapeutic Option for Colorectal Cancer: An In-Silico Pharmaco-Informatics Investigation

Evaluation of SYK Gene as a Prognostic Biomarker and Suggested Aromatic Potential Phytochemicals to Halt the Colorectal Cancer

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