Cheminformatics and Pharmacological Network Analysis for the Prediction of Molecular Mechanism of Herbal Drug Ligands

Mapping Intimacies ◽

10.21203/rs.3.rs-961457/v1 ◽

2021 ◽

Author(s):

Lalit Raj Singh

Keyword(s):

Network Analysis ◽

Medicinal Plants ◽

Mechanism Of Action ◽

In Silico ◽

Drug Repurposing ◽

Cyperus Rotundus ◽

Herbal Drug ◽

Global Demand ◽

Herbal Medications ◽

Genomic Relationships

Abstract The global demand for safer and more therapeutically effective medications is surging, providing medicinal plants a boost as suppliers of lead particles. The focus of current research is on an in silico comparison of one major bioactive principle and curatively designed new small drug-like molecule (scaffold analog). The recent study confirmed that the plant belongs to the Cyperaceae family and that it is Cyperus rotundus L. in taxonomy. The study's purpose was to uncover the mechanism of action of ligands/ scaffold analog by revealing genomic relationships, cellular signaling, and the top ten diseases/ illnesses that they were linked to. The scaffold analog showed promising drug-like potential as compared with cyperene. These investigations could broaden the reach of herbal medications, provide new formulations for current diseases or disorders, and pave the door for drug repurposing.

Download Full-text

Ayurvedic Medicinal Plants Against COVID-19: An In Silico Analysis

Natural Product Communications ◽

10.1177/1934578x211056753 ◽

2021 ◽

Vol 16 (11) ◽

pp. 1934578X2110567

Author(s):

Bharat Krushna Khuntia ◽

Vandna Sharma ◽

Sahar Qazi ◽

Soumi Das ◽

Shruti Sharma ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Medicinal Plants ◽

Binding Affinity ◽

In Silico ◽

In Silico Analysis ◽

Cyperus Rotundus ◽

Effective Control ◽

Picrorhiza Kurroa ◽

Silico Analysis

Even after one and a half years since the outbreak of COVID-19, its complete and effective control is still far from being achieved despite vaccination drives, symptomatic management with available drugs, and wider lockdowns. This has inspired researchers to screen potential phytochemicals from medicinal plants against SARS-CoV-2, adopting a bio-informatics approach. The current study aimed to assess anti-viral activity of the phytochemicals derived from Ayurvedic medicinal plants against SARS-CoV-2 drug targets [3-chymotrypsin-like protease (3CLpro) and RNA dependent RNA polymerase (RdRp)] using validated in silico methods.3D Structures of 196 phytochemicals from three Ayurvedic plants were retrieved from PubChem and KNApSAcK databases and screened for Absorption Distribution Metabolism Excretion and Toxicity(ADMET) to predict drug-likeness. The phytochemicals were subjected to molecular docking and only three showed promise: Acetovanillonewith a binding affinity of −4.7Kcal/mol with RdRp and −4.1 Kcal/mol with 3CL pro; myrtenol with equivalent values of −4.3 Kcal/mol with RdRP and −3.2 Kcal/mol with 3CLpro; and nimbochalcin with equivalent values of −5.0Kcal/mol with RdRp and −4.9 Kcal/mol with 3CLpro. Molecular dynamics simulation (50ns) analysis was made of 3CLpro and RdRp using Autodock Vina 1.1.2 software and VMD software. After ADMET analysis, 78 phytochemicals were found suitable for molecular docking. Three, namely acetovanillone, myrtenol and nimbochalcin from Picrorhiza kurroa, Azadirachta indica and Cyperus rotundus,respectively,exhibited good binding affinity with 3CLproand RdRp of SARS-CoV-2. Interaction analysis, molecular dynamics simulations and MM-PBSA calculations were executed for two complexes, acetovanillone_RdRp and myrtenol_3CL pro.Acetovanillone_RdRpcomplex did not display any structural change after MD simulation as compared to myrtenol_3CL pro. The overall stability of acetovanillone_6NUR was 154.7 kJ/mol, and for myrtenol_1UJ1 90.5 kJ/mol. In silico analysis revealed that acetovanillone ( Picrorhiza kurroa) and myrtenol ( Cyperus rotundus) possess anti SARS-CoV-2 activity. Further studies are needed to validate their efficacy in biological models.

Download Full-text

Faculty Opinions recommendation of In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1115434.14726302 ◽

2011 ◽

Author(s):

Patrick Duffy

Keyword(s):

High Throughput ◽

Mechanism Of Action ◽

In Silico ◽

High Throughput Screen ◽

Activity Profiling

Download Full-text

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999200824115536 ◽

2020 ◽

Vol 23 ◽

Author(s):

Sisir Nandi ◽

Mohit Kumar ◽

Mridula Saxena ◽

Anil Kumar Saxena

Keyword(s):

Molecular Docking ◽

In Silico ◽

Drug Repurposing ◽

Clinical Settings ◽

The Novel ◽

In Silico Docking ◽

Biochemical Mechanisms ◽

Novel Coronavirus ◽

In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

Download Full-text

Drug repurposing using similarity-based target prediction, docking studies and scaffold hopping of lefamulin

Letters in Drug Design & Discovery ◽

10.2174/1570180817999201201113712 ◽

2020 ◽

Vol 17 ◽

Author(s):

Shikha Sharma ◽

Shweta Sharma ◽

Vaishali Pathak ◽

Parwinder Kaur ◽

Rajesh Kumar Singh

Keyword(s):

In Silico ◽

Target Prediction ◽

Drug Repurposing ◽

Docking Studies ◽

Target Protein ◽

Future Perspective ◽

Antibacterial Drug ◽

Scaffold Hopping ◽

Target Proteins ◽

Renin Inhibitors

Aim: To investigate and validate the potential target proteins for drug repurposing of newly FDA approved antibacterial drug. Background: Drug repurposing is the process of assigning indications for drugs other than the one(s) that they were initially developed for. Discovery of entirely new indications from already approved drugs is highly lucrative as it minimizes the pipeline of the drug development process by reducing time and cost. In silico driven technologies made it possible to analyze molecules for different target proteins which are not yet explored. Objective: To analyze possible targets proteins for drug repurposing of lefamulin and their validation. Also, in silico prediction of novel scaffolds from lefamulin has been performed for assisting medicinal chemists in future drug design. Methods: A similarity-based prediction tool was employed for predicting target protein and further investigated using docking studies on PDB ID: 2V16. Besides, various in silico tools were employed for prediction of novel scaffolds from lefamulin using scaffold hopping technique followed by evaluation with various in silico parameters viz., ADME, synthetic accessibility and PAINS. Results: Based on the similarity and target prediction studies, renin is found as the most probable target protein for lefamulin. Further, validation studies using docking of lefamulin revealed the significant interactions of lefamulin with the binding pocket of the target protein. Also, three novel scaffolds were predicted using scaffold hopping technique and found to be in the limit to reduce the chances of drug failure in the physiological system during the last stage approval process. Conclusion: To encapsulate the future perspective, lefamulin may assist in the development of the renin inhibitors and, also three possible novel scaffolds with good pharmacokinetic profile can be developed into both as renin inhibitors and for bacterial infections.

Download Full-text

In Silico Docking, ADMET and QSAR Study of few Antimalarial Phytoconstituents as Inhibitors of Plasmepsin II of P. falciparum Against Malaria

Current Drug Therapy ◽

10.2174/1574885514666190923112738 ◽

2020 ◽

Vol 15 (3) ◽

pp. 264-273

Author(s):

Syeda Sabiha Salam ◽

Pankaj Chetia ◽

Devid Kardong

Keyword(s):

Medicinal Plants ◽

In Silico ◽

Computational Study ◽

Binding Energies ◽

Eastern Region ◽

Relationship Analysis ◽

The North ◽

North Eastern ◽

Plasmepsin Ii ◽

Antimalarial Compounds

Background: Malaria is endemic in various parts of India particularly in the North- Eastern states with Plasmodium falciparum-the most prevalent human malaria parasite. Plantderived compounds have always received tremendous importance in the area of drug discovery and development and scientific study of traditional medicinal plants are of great importance to mankind. Objective: The present work deals with the computational study of some antimalarial compounds obtained from a few medicinal plants used by the tribal inhabitants of the North-Eastern region of India for treating malaria. Methods: In silico methodologies were performed to study the ligand-receptor interactions. Target was identified based on the pharmacophore mapping approach. A total of 18 plant-derived compounds were investigated in order to estimate the binding energies of the compounds with their drug target through molecular docking using Autodock 4.2. ADMET filtering for determining the pharmacokinetic properties of the compounds was done using Mobyle@RPBS server. Subsequent Quantitative-Structure Activity Relationship analysis for bioactivity prediction (IC50) of the compounds was done using Easy QSAR 1.0. Results: The docking result identified Salannin to be the most potent Plasmepsin II inhibitor while the QSAR analysis identified Lupeol to have the least IC50 value. Most of the compounds have passed the ADME/Tox filtration. Conclusion: Salannin and Lupeol were found to be the most potent antimalarial compounds that can act as successful inhibitors against Plasmepsin II of P. falciparum. The compounds Salannin and Lupeol are found in Azadirachta indica and Swertia chirata plants respectively, abundantly available in the North-Eastern region of India and used by many inhabiting tribes for the treatment of malaria and its symptoms.

Download Full-text

Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666190916141934 ◽

2019 ◽

Vol 18 (8) ◽

pp. 581-597 ◽

Cited By ~ 1

Author(s):

Ambreen Fatima ◽

Yasir Hasan Siddique

Keyword(s):

Medicinal Plants ◽

Mechanism Of Action ◽

Neurodegenerative Disorders ◽

Treatment Strategies ◽

Dietary Supplementation ◽

Plant Polyphenols ◽

Promising Candidate ◽

Naturally Occurring ◽

The Brain

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

Download Full-text