Identification of tyrosine kinase inhibitors from Panax bipinnatifidus and Panax pseudoginseng for RTK—HER2 and VEGFR2 receptors, by in silico approach

Paul, Dipayan; Mahanta, Saurov; Tag, Hui; Das, Sanjib Kumar; Gupta, Debmalya Das; Tanti, Bhaben; Ananthan, R.; Das, Ranjan; Jambhulkar, Sanjay; Hui, Pallabi K.

doi:10.1007/s11030-021-10304-5

Cited by 16 publications

(13 citation statements)

References 46 publications

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“…The predicted 3D structure of the SARS-CoV-2 M protein was processed and prepared for Molecular Docking in Protein Preparation Wizard of Epik module of Schrödinger Suite, 2020-3 ( Paul et al, 2021 ). The similar binding sites and excess water molecules in the protein structure were removed, and the bond orders were refined.…”

Section: Methodsmentioning

confidence: 99%

“…Using the Prime module of Schrodinger Suite, 2020-3, the missing chain atoms were added ( Suganya et al, 2014 ). Further, the 3D structure of the protein was minimized using Optimized Potentials For Liquid Simulations-3 (OPLS3e) molecular force field with RMSD (Root Mean Square Deviation) of crystallographic heavy atoms which were kept at 0.3Å ( Paul et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

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Plant Source Derived Compound Exhibited In Silico Inhibition of Membrane Glycoprotein In SARS-CoV-2: Paving the Way to Discover a New Class of Compound For Treatment of COVID-19

Mahanta¹,

Naiya

Biswas

et al. 2022

Front. Pharmacol.

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SARS-CoV-2 is the virus responsible for causing COVID-19 disease in humans, creating the recent pandemic across the world, where lower production of Type I Interferon (IFN-I) is associated with the deadly form of the disease. Membrane protein or SARS-CoV-2 M proteins are known to be the major reason behind the lower production of human IFN-I by suppressing the expression of IFNβ and Interferon Stimulated Genes. In this study, 7,832 compounds from 32 medicinal plants of India possessing traditional knowledge linkage with pneumonia-like disease treatment, were screened against the Homology-Modelled structure of SARS-CoV-2 M protein with the objective of identifying some active phytochemicals as inhibitors. The entire study was carried out using different modules of Schrodinger Suite 2020-3. During the docking of the phytochemicals against the SARS-CoV-2 M protein, a compound, ZIN1722 from Zingiber officinale showed the best binding affinity with the receptor with a Glide Docking Score of −5.752 and Glide gscore of −5.789. In order to study the binding stability, the complex between the SARS-CoV-2 M protein and ZIN1722 was subjected to 50 ns Molecular Dynamics simulation using Desmond module of Schrodinger suite 2020-3, during which the receptor-ligand complex showed substantial stability after 32 ns of MD Simulation. The molecule ZIN1722 also showed promising results during ADME-Tox analysis performed using Swiss ADME and pkCSM. With all the findings of this extensive computational study, the compound ZIN1722 is proposed as a potential inhibitor to the SARS-CoV-2 M protein, which may subsequently prevent the immunosuppression mechanism in the human body during the SARS-CoV-2 virus infection. Further studies based on this work would pave the way towards the identification of an effective therapeutic regime for the treatment and management of SARS-CoV-2 infection in a precise and sustainable manner.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Plant Source Derived Compound Exhibited In Silico Inhibition of Membrane Glycoprotein In SARS-CoV-2: Paving the Way to Discover a New Class of Compound For Treatment of COVID-19

Mahanta¹,

Naiya

Biswas

et al. 2022

Front. Pharmacol.

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“…Although the actual mode of action of most of these chemicals is still unknown, screening of some effective plant metabolites and detailed analyses will generate treasures of effective natural medicines in the future. Although out of the purview of this present review, many interesting receptor kinase inhibitors have already been reported from plants to inhibit spread of cancerous tissues (Paul et al 2021). Natural medicines derived from plant products are mostly non-toxic, well-tolerated with minimum side effects, and highly absorptive in nature by the immunogenic pathways of the human body.…”

Section: Introductionmentioning

confidence: 93%

Natural therapeutics against SARS CoV2: the potentiality and challenges

Bhar

Jain

Das

2022

Vegetos

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The incidence of the COVID-19 pandemic completely reoriented global socio-economic parameters and human civilization have experienced the worst situation in the recent past. The rapid mutation rates in viruses have continuously been creating emerging variants of concerns (VOCs) which devastated different parts of the world with subsequent waves of infection. Although, series of antiviral drugs and vaccines were formulated but cent percent effectiveness of these drugs is still awaited. Many of these drugs have different side effects which necessitate proper trial before release. Plants are the storehouse of antimicrobial metabolites which have also long been utilized as traditional medicines against different viral infections. Although, proper mechanism of action of these traditional medicines are unknown, they may be a potential source of effective anti-COVID drug for future implications. Advanced bioinformatic applications have opened up a new arena in predicting these repurposed drugs as a potential COVID mitigator. The present review summarizes brief accounts of the corona virus with their possible entry mechanism. This study also tries to classify different possible anti COVID-19 plant-derived metabolites based on their probable mode of action. This review will surely provide useful information on repurposed drugs to combat COVID-19 in this critical situation.

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“…The local tribal communities of the Eastern Himalayan region of India use the rhizome as an antidote for snake and insect poison [17]. The steroidal saponins are the major class of compounds reported from Paris polyphylla rhizomes and also comprise triterpenoid saponins [18,19], while steroidal saponins such as dioscin, polyphyllin D, and balanitin 7 are reported as bioactive phytocompounds from the rhizome of P. polyphylla Smith [20]. Recent phytochemical studies on P. polyphylla from Eastern Himalaya have confirmed the diosgenin and other steroidal saponins, namely, pennogenin and 7-Ketodiosgenin acetate as major bioactive phytoconstituents [19].…”

Section: Introductionmentioning

confidence: 99%

“…The steroidal saponins are the major class of compounds reported from Paris polyphylla rhizomes and also comprise triterpenoid saponins [18,19], while steroidal saponins such as dioscin, polyphyllin D, and balanitin 7 are reported as bioactive phytocompounds from the rhizome of P. polyphylla Smith [20]. Recent phytochemical studies on P. polyphylla from Eastern Himalaya have confirmed the diosgenin and other steroidal saponins, namely, pennogenin and 7-Ketodiosgenin acetate as major bioactive phytoconstituents [19]. However, molecular docking studies of individual phytoconstituents (steroidal saponins) of P. polyphylla effective against specific breast cancer receptors are not reported to date.…”

Section: Introductionmentioning

confidence: 99%

Identification of phytocompounds from Paris polyphylla Smith as potential inhibitors against two breast cancer receptors (ER\a and EGFR tyrosine kinase) through chromatographic and In silico approaches

Gupta¹,

Mahanta²,

Das³

et al. 2022

J App Biol biotech

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In the current decade, the potential side effects caused by synthetic kinase domain inhibitors have paved the way for developing an alternative anti-breast cancer drug from botanical sources. Estrogen receptor-α (ERα) and epidermal growth factor receptor (EGFR) tyrosine kinase receptors play a key role in the activation of genomic and nongenomic related pathways of breast cancer progression. Paris polyphylla Smith (Melanthiaceae) is a rich source of steroidal saponins reported as an anti-breast cancer agent used among the local communities of Asian countries. In the present study, a total of 116 phytocompounds were characterized and identified from P. polyphylla rhizomes using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry tools. They were subjected to virtual screening, molecular docking, and molecular simulation analysis with these two breast cancer receptors. Among them, only three steroidal saponins, namely, diosgenin, pennogenin, and 7-ketodiosgenin acetate binding affinity with target receptors were on the higher side when compared with natural ligands. The highest affinity for the receptors ERα and EGFR tyrosine kinase was shown by 7-ketodiosgenin acetate with docking scores of −10.4 Kcal/mol and −11.2 Kcal/mol, respectively, followed by diosgenin and pennogenin. LigPlot + analysis revealed that the selected three steroidal saponins utilized a combination of hydrogen bonding and hydrophobic interactions to align themselves more efficiently in the ligand-binding pocket of the target receptors. Molecular simulation analysis revealed a stable interaction between the phytocompounds and the target receptors. Lipinski's rule confirmed pennogenin as the best phytocompound that could be used as a potential inhibitor against the two target breast cancer receptors (ERα and EGFR tyrosine kinase).

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Identification of tyrosine kinase inhibitors from Panax bipinnatifidus and Panax pseudoginseng for RTK—HER2 and VEGFR2 receptors, by in silico approach

Cited by 16 publications

References 46 publications

Plant Source Derived Compound Exhibited In Silico Inhibition of Membrane Glycoprotein In SARS-CoV-2: Paving the Way to Discover a New Class of Compound For Treatment of COVID-19

Plant Source Derived Compound Exhibited In Silico Inhibition of Membrane Glycoprotein In SARS-CoV-2: Paving the Way to Discover a New Class of Compound For Treatment of COVID-19

Natural therapeutics against SARS CoV2: the potentiality and challenges

Identification of phytocompounds from Paris polyphylla Smith as potential inhibitors against two breast cancer receptors (ER\a and EGFR tyrosine kinase) through chromatographic and In silico approaches

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