Computational Investigations for Identification of Bioactive Molecules from Baccaurea ramiflora and Bergenia ciliata as Inhibitors of SARS-CoV-2 Mpro

Zothantluanga, James H.; Abdalla, Mohnad; Rudrapal, Mithun; Tian, Qiang; Chetia, Dipak; Li, Jin

doi:10.1080/10406638.2022.2046613

Cited by 28 publications

(8 citation statements)

References 95 publications

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“…Molecular dynamics simulation (MDS) helps study the protein–ligand complex’s structural stability and flexibility. In this study, MDS was performed for the top hit compounds to legitimize the protein–ligand complex (PLC) and measure the ligand-binding constancy in the active site of the selected target 53 , 54 . MDS was carried out using the Desmond module of the Schrödinger Suite developed by the D.E.…”

Section: Methodsmentioning

confidence: 99%

Dual synergistic inhibition of COX and LOX by potential chemicals from Indian daily spices investigated through detailed computational studies

Rudrapal,

Eltayeb,

Rakshit

et al. 2023

Sci Rep

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Cyclooxygenase (COX) and Lipoxygenase (LOX) are essential enzymes for arachidonic acid (AA) to eicosanoids conversion. These AA-derived eicosanoids are essential for initiating immunological responses, causing inflammation, and resolving inflammation. Dual COX/5-LOX inhibitors are believed to be promising novel anti-inflammatory agents. They inhibit the synthesis of prostaglandins (PGs) and leukotrienes (LTs), but have no effect on lipoxin formation. This mechanism of combined inhibition circumvents certain limitations for selective COX-2 inhibitors and spares the gastrointestinal mucosa. Natural products, i.e. spice chemicals and herbs, offer an excellent opportunity for drug discovery. They have proven anti-inflammatory properties. However, the potential of a molecule to be a lead/ drug candidate can be much more enhanced if it has the property of inhibition in a dual mechanism. Synergistic activity is always a better option than the molecule's normal biological activity. Herein, we have explored the dual COX/5-LOX inhibition property of the three major potent phytoconsituents (curcumin, capsaicin, and gingerol) from Indian spices using in silico tools and biophysical techniques in a quest to identify their probable inhibitory role as anti-inflammatory agents. Results revealed the dual COX/5-LOX inhibitory potential of curcumin. Gingerol and capsaicin also revealed favorable results as dual COX/5-LOX inhibitors. Our results are substantiated by target similarity studies, molecular docking, molecular dynamics, energy calculations, DFT, and QSAR studies. In experimental inhibitory (in vitro) studies, curcumin exhibited the best dual inhibitory activities against COX-1/2 and 5-LOX enzymes. Capsaicin and gingerol also showed inhibitory potential against both COX and LOX enzymes. In view of the anti-inflammatory potential these spice chemicals, this research could pave the way for more scientific exploration in this area for drug discovery.

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Section: Methodsmentioning

confidence: 99%

Dual synergistic inhibition of COX and LOX by potential chemicals from Indian daily spices investigated through detailed computational studies

Rudrapal,

Eltayeb,

Rakshit

et al. 2023

Sci Rep

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“…ADMET studies were used to examine different bioavailability‐related properties on a few software [19] . The properties of ligands such as lipophilicity, water solubility, BBB permeability, and gastrointestinal absorption are also described.…”

Section: Resultsmentioning

confidence: 99%

“…ADMET studies were used to examine different bioavailabilityrelated properties on a few software. [19] The properties of ChemistrySelect ligands such as lipophilicity, water solubility, BBB permeability, and gastrointestinal absorption are also described. With drug similarity, it is qualitatively evaluated that the molecule can be an oral drug in terms of bioavailability.…”

Section: Computational Admet Studiesmentioning

confidence: 99%

Virtual Screening, Molecular Docking, Molecular Dynamics and ADMET Studies on the OTU Protease of Crimean‐Congo Hemorrhagic Fever Virus

Yildirim

Çeli̇k

2022

ChemistrySelect

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Crimean-Congo hemorrhagic fever (CCHF) is caused by the Nairovirus genus CCHF virus from the Bunyaviridae family, which is called by the same name. The effective reservoir for the spread of the virus is the ticks of the genus Hyalomma. The CCHF disease has a mortality rate of 30 % in the world and 5 % in Turkey. Although it has a high mortality rate, there is only one approved drug available to treat the disease. Currently, ribavirin is the only drug approved by the WHO (World Health Organization) for the CCHF virus. However, although it has been proven to be effective in the early diagnosis of the disease in non-randomized studies, there is still controversial due to the lack of randomized studies. OTU (ovarian tumor), an enzyme that plays a role in viral replication and suppression of the immune system, was chosen as a protease drug target. Computer-aided drug design aims to increase the success rate while reducing the time and budget spent. Virtual screening, molecular docking, molecular dynamics simulations and AD-MET studies are stages of computer-aided drug design. In this thesis; as a result of virtual scanning and molecular docking study, the active ingredients of protokylol, rimiterol, and aspoxicillin, which have high values on the OTU protease enzyme of CCHF, were selected. Then, ligand enzyme complexes were investigated by molecular dynamics simulations and ADMET studies.

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“…Molecular docking was performed with the AutoDockVina to investigate the binding affinity of vasicine toward each target proteins. Discovery Studio Visualizer 2020 was used for the visualization of protein-ligand interactions ( 43 , 50 – 53 ). The drug-likeness of vasicine was studied using Swiss ADME ( 54 – 57 ).…”

Section: Methodsmentioning

confidence: 99%

Valorization of Adhatoda vasica leaves: Extraction, in vitro analyses and in silico approaches

et al. 2023

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Adhatoda vasica (also called Vasaka) is a traditional medicinal herb used traditionally for the relief of cough, asthma, nasal congestion, bronchial inflammation, upper respiratory infections, bleeding disorders, skin diseases, leprosy, tuberculosis, diabetes, allergic conditions, rheumatism, tumor, and many more diseases. The present study aims to investigate the biological activities of vasicine, a potent alkaloid from A. vasica with different biological/ pharmacological assays and in silico techniques. Vasicine showed antimicrobial activity as evidenced fromthe colony-forming unit assay. It showed antioxidant activity in ABTS scavenging assay (IC50 = 11.5 μg/ml), ferric reducing power assay (IC50 = 15 μg/ml), DPPH radical scavenging assay (IC50 = 18.2 μg/ml), hydroxyl radical scavenging assay (IC50 = 22 μg/ml), and hydrogen peroxide assay (IC50 = 27.8 μg/ml). It also showed anti-inflammatory activity in proteinase inhibitory assay (IC50 = 76 μg/ml), BSA method (IC50 = 51.7 μg/ml), egg albumin method (IC50 = 53.2 μg/ml), and lipooxygenase inhibition assay (IC50 = 76 μg/ml). Vasicine showed antidiabetic activity in α-amylase inhibition assay (IC50 = 47.6 μg/ml), α-glucosidase inhibition assay (IC50 = 49.68 μg/ml), and non-enzymatic glycosylation of hemoglobin assay. It showed antiviral activity against HIV-protease (IC50 = 38.5 μg/ml). Vasicine also showed anticancer activity against lung cancer cells (IC50 = 46.5 μg/ml) and human fibroblast cells (IC50 = 82.5 μg/ml). In silico studies revealed that similar to the native ligands, vasicine also showed a low binding energy, i.e., good binding affinity for the active binding sites and interacted with α-amylase (-6.7 kcal/mol), α-glucosidase (-7.6 kcal/mol), cyclooxygenase (-7.4 kcal/mol), epidermal growth factor receptor (-6.4 kcal/mol), lipooxygenase (-6.9 kcal/mol), and HIV-protease (-6.4 kcal/mol). The present study ascertains the potential of vasicine as a bioactive compound isolated from A. vasica having therapeutic usefulness in many human diseases.

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Computational Investigations for Identification of Bioactive Molecules from Baccaurea ramiflora and Bergenia ciliata as Inhibitors of SARS-CoV-2 M^pro

Cited by 28 publications

References 95 publications

Dual synergistic inhibition of COX and LOX by potential chemicals from Indian daily spices investigated through detailed computational studies

Dual synergistic inhibition of COX and LOX by potential chemicals from Indian daily spices investigated through detailed computational studies

Virtual Screening, Molecular Docking, Molecular Dynamics and ADMET Studies on the OTU Protease of Crimean‐Congo Hemorrhagic Fever Virus

Valorization of Adhatoda vasica leaves: Extraction, in vitro analyses and in silico approaches

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