In silico molecular docking studies and ADME/T analysis of Some Flavonoids against the target of Mpro inCOVID-19

2020 ◽  
Vol 10 (2) ◽  
pp. 33-46
Author(s):  
Kaviarasu J ◽  
Suresh Kumar CA ◽  
Naimuddeen N
Keyword(s):  
Binding Energy ◽  
Development Process ◽  
Docking Studies ◽  
Lung Damage ◽  
Effective Vaccine ◽  
Kcal Mole ◽  
Respiratory Complications ◽  
Global Pandemic ◽  
In Silico Molecular Docking ◽  
Native Ligand

COVID-19 may be a devastating global pandemic round the world. While the bulk of infected cases appear mild, in some cases individuals present respiratory complications with possible serious lung damage. This virus can infect both animals and other people and its control are very difficult because there's no effective vaccine or drugs available in markets for the treatments for COVID-19 so far. During this study we docked the flavonoids against the target protein Mpro(6lu7) shows the binding energy between -8.68 kcal/mole to -6. 68 kcal/mol compare to native ligand (PRD_002214). The compounds Catechins, Luteoforol, Sappanchal-cone, Baicalein, Vitexin, Chrysosplenol, 5,6,7-Trimeth-oxyflavone showed almost equal binding energy towards the native ligand except Genistein. Our analyses revealed that the highest nine hits might function potential anti- SARS-CoV-2 lead molecules for further innovation and drug development process to combat COVID-19 also nearly as good drug likeness properties studied supported the Lipinski’s rules of 5.

scholarly journals STRUCTURE-BASED DOCKING STUDIES TOWARD EXPLORING THE POTENTIAL ANTICANCER ACTIVITY OF MORIN AGAINST NON-MELANOMA SKIN CANCER THERAPEUTIC DRUG TARGETS

2018 ◽  
Vol 11 (4) ◽  
pp. 61
Author(s):  
Anjugam C ◽  
Sridevi M ◽  
Gnanendra Ts
Keyword(s):  
Binding Energy ◽  
Anticancer Activity ◽  
Drug Targets ◽  
Docking Studies ◽  
Therapeutic Drug ◽  
Peroxisome Proliferator ◽  
Non Melanoma Skin Cancer ◽  
Cox 2 ◽  
Peroxisome Proliferator Activated Receptors ◽  
In Silico Molecular Docking

 Objective: The purpose of this study is to explore the anticancer activity of morin compound against human cyclooxygenase-2 (COX-2) and peroxisome-proliferator-activated receptors (PPARs) isotypes (PPARα and PPARγ) through in silico molecular docking studies.Methods: The 3D structures of human COX-2 complexed with ibuprofen (PDB ID: 4PH9), PPARα complexed with a synthetic agonist (2S)-2-(4- methoxy-3-{[(pyren-1-yl carbonyl) amino] methyl} benzyl) butanoic acid (PDB ID: 3VI8) and PPARγ complexed indomethacin (PDB ID: 3ADX) were retrieved from protein databank. The cocrystallized sites were considered as binding sites, and the docking with morin compound was performed along with their respective cocrystals for each target and compared their interactions and binding affinities.Results: It is observed that the morin compound exhibited better binding energy of -32.9528 kJ/mol against PPARα followed by COX-2 (binding energy: −18.4311 kJ/mol) and PPARγ (binding energy: −17.4228 kJ/mol) when compared to their cocrystallized ligands.Conclusion: The present study suggests that morin compound might serve as potential alternatives in the prevention of skin cancers by showing better activity against PPARα.

Ajmalicine and its Analogues Against AChE and BuChE for the Management of Alzheimer’s Disease: An In-silico Study

2020 ◽  
Vol 26 (37) ◽  
pp. 4808-4814
Author(s):  
Shu Liu ◽  
Minyan Dang ◽  
Yan Lei ◽  
Syed S. Ahmad ◽  
Mohammad Khalid ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Binding Energy ◽  
3D Structure ◽  
Docking Studies ◽  
Kcal Mole ◽  
In Silico Study ◽  
Phytochemical Compounds ◽  
Inhibitory Potential ◽  
Potential Inhibitors

Background: Alzheimer's disease (AD) is the most well-known reason for disability in persons aged greater than 65 years worldwide. AD influences the part of the brain that controls cognitive and non-cognitive functions. Objective: The study focuses on the screening of natural compounds for the inhibition of AChE and BuChE using a computational methodology. Methods: We performed a docking-based virtual screening utilizing the 3D structure of AChE and BuChE to search for potential inhibitors for AD. In this work, a screened inhibitor Ajmalicine similarity search was carried out against a natural products database (Super Natural II). Lipinski rule of five was carried out and docking studies were performed between ligands and enzyme using ‘Autodock4.2’. Results: wo phytochemical compounds SN00288228 and SN00226692 were predicted for the inhibition of AChE and BuChE, respectively. The docking results revealed Ajmalicine, a prominent natural alkaloid, showing promising inhibitory potential against AChE and BuChE with the binding energy of -9.02 and -8.89 kcal/mole, respectively. However, SN00288228- AChE, and SN00226692-BuChE were found to have binding energy -9.88 and -9.54 kcal/mole, respectively. These selected phytochemical compounds showed better interactions in comparison to Ajmalicine with the target molecule. Conclusion: The current study verifies that SN00288228 and SN00226692 are more capable inhibitors of human AChE and BuChE as compared to Ajmalicine with reference to ΔG values.

scholarly journals Is ACE2 a friend or foe in the fight against the COVID19 pandemic?

2020 ◽  
Author(s):  
Nafis Hossain
Keyword(s):  
Viral Entry ◽  
Ace Inhibitor ◽  
Degradation Products ◽  
Protective Role ◽  
Lung Damage ◽  
Ang Ii ◽  
Respiratory Complications ◽  
Major Barrier ◽  
Viral Attachment ◽  
Global Pandemic

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for an unprecedented global pandemic that has prompted attempts to mitigate its rapid transmission. A major barrier has been a limited understanding of the mechanisms that underlie its pathogenesis. Angiotensin converting enzyme (ACE) 2 may be an important receptor that the virus targets to establish infection, and this is upregulated with ACE inhibitor and angiotensin-receptor blocker (ARB) therapy. It has been suggested that avoidance of ACE inhibitor/ARB therapy may be advisable due to the theoretical risk of SARS-CoV-2 infection in these patients. A review of the literature to further investigate this possibility corroborated the significance of ACE2 for viral entry of SARS-CoV-2. However, the development of potentially fatal respiratory complications (i.e. acute respiratory distress syndrome; ARDS) appears to be influenced by a downregulation of ACE2 activity, rather than an increase. The literature suggests ACE2 has a protective role against lung injury by cleaving angiotensin II (Ang II). The effects of this are twofold: accumulated Ang II is associated with more pronounced lung deterioration, and the loss of its degradation products that have anti-inflammatory properties enables unopposed lung damage to take place. There is emerging evidence that this is also true for SARS-CoV-2 infection; increased viral load is associated with higher Ang II and extent of lung damage. Overall, the evidence indicates that viral attachment decreases, rather than increases, ACE2 activity which may contribute to the respiratory complications seen in severe cases. As such, discontinuation of ACE inhibitor/ARB therapy is currently not warranted.

Molecular Docking Studies for Protein-Targeted Drug Development in SARS-CoV-2

2021 ◽  
Vol 18 ◽  
Author(s):  
Ahmad Dzulfikri Nurhan ◽  
Maria Apriliani Gani ◽  
Saipul Maulana ◽  
Siswandono Siswandono ◽  
Chrismawan Ardianto ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Docking Studies ◽  
Binding Energies ◽  
Spike Glycoprotein ◽  
Protein Targets ◽  
Lipinski’S Rule ◽  
Global Pandemic ◽  
Potential Inhibitors ◽  
3Cl Protease

Background: The SARS-CoV-2/COVID-19 infection has resulted in a global pandemic and emergency. Currently, there is no therapeutic agent that has been proven to be effective and selective to deal with this pandemic. Objective: In this study, we explored and screened 401 compounds-related viruses that may inhibit one or more of the three protein targets in SARS-CoV-2 (3CL protease, RdRp, and spike glycoprotein) using in-silico approach. Methods: Lipinski's rule of five was used as an initial screening for these compounds. Ligand preparation was carried out using JChem software and Schrödinger's LigPrep module, while protein elucidation used AutoDockTools-1.5.6. Molecular docking was analyzed using AutoDockVina. Results: A total of five compounds-related viruses were obtained from each SARS-CoV-2 protein with ideal and potential binding energy as a candidate for target protein inhibitor on SARS-CoV-2. At the protein 3CL protease imatinib, TAK-981, lopinavir, mefloquine, and sitagliptin were found to be potential inhibitors of this protein. In the protein RdRp tetrandrine, relacatib, AZD7986, imatinib, and TAK-981 revealed potential as an inhibitor of this protein. At the protein spike, glycoprotein AZD7986, selinexor, imatinib, lopinavir, and ciclesonide, were found to have potential as inhibitors of these proteins. All these compounds have better binding energy than the three comparator drugs (remdesivir, chloroquine, and hydroxychloroquine). Conclusion: We have obtained several compounds-related viruses with reliable binding energies to the SARS-CoV-2 proteins and potentially better than the three comparator drugs. Furthermore, this research will pave the way for accelerating the development of Covid-19 drugs.

scholarly journals STRUCTURE PREDICTION AND IN SILICO DESIGNING OF DRUGS AGAINST KALLIKREIN PROTEIN 12

2017 ◽  
Vol 9 (2) ◽  
pp. 64
Author(s):  
Manish Devgan
Keyword(s):  
Binding Energy ◽  
In Silico ◽  
Structure Prediction ◽  
Docking Studies ◽  
Receptor Protein ◽  
Loop Modeling ◽  
Autodock Vina ◽  
Potential Therapeutic Target ◽  
Plot Analysis ◽  
In Silico Molecular Docking

Objective: Human Kallikrein protein 12 (hK12) might serve as a novel diagnostic and prognostic biomarker, as well as a potential therapeutic target, in gastric cancer.Methods: In this work, a theoretical model of hK12 receptor protein was generated using the concepts of homology modeling and loop modeling. The resulting model was validated with Ramachandran plot analysis. The ligands generated with the help of Drug bank were docked against hK12 receptor protein using AutoDock Vina in PyRx 0.8. The structure of ligand DB04786 (Suramin), with least binding energy, was varied by using ACD/ChemSketch 8.0 and the docking was done for the resulting 16 new ligands.Results: The results indicated that the ligand10 bears the minimum binding energy (-12.3 Kcal/mol) with the target protein and thus the prospects of binding are high. The results also clearly demonstrated that the in silico molecular docking studies of selected ligands, i.e., suramin, ligands 5, 6, 10 and 16 with hK12 protein exhibited favourable binding interactions and warranted.Conclusion: Further studies needed for the development of potent inhibitors for the overexpression of hK12 protein making the management of gastric cancer more efficient.

scholarly journals In silico molecular docking of quercetin as anti-colorectal cancer agents by inhibiting LT4AH

2021 ◽  
Vol 1 (2) ◽  
pp. 16
Author(s):  
Made Agus Widiana Saputra ◽  
Anak Agung Istri Rani Mahaswari ◽  
Ni Ketut Sri Anggreni ◽  
Wahyu Nadi Eka Putri ◽  
Ni Putu Linda Laksmiani
Keyword(s):  
Colorectal Cancer ◽  
Molecular Docking ◽  
Binding Energy ◽  
In Silico ◽  
Malignant Neoplasm ◽  
Docking Method ◽  
Leukotriene A4 Hydrolase ◽  
Leukotriene A4 ◽  
In Silico Molecular Docking ◽  
Native Ligand

Colorectal cancer is a malignant neoplasm originating from the colon or rectum. Overexpression of leukotriene A4 hydrolase (LTA4H) increases the growth of HCT116 colon cancer cells, therefore, this enzyme becomes an attractive target for commercial drug bestatin. Meanwhile, quercetin is a member of flavonoids possessing a wide variety of anticancer. This study aimed to determine the potential of quercetin as anti-colorectal cancer by inhibiting LTA4H through in silico molecular docking. The docking process involved optimizing quercetin structure, preparing LTA4H protein (PDB ID: 3U9W), validating the molecular docking method, and docking quercetin and bestatin on LTA4H. The binding energy of quercetin to LTA4H was -9.57 kcal/mol, while 28P native ligand and bestatin yielded -10.22 kcal/mol and -9.10 kcal/mol, respectively. Based on the binding energy value, quercetin has a potential inhibitory against the LTA4H.

scholarly journals Are the SARS-CoV-2 Variants Greater Threats? - An In Silico Analysis of the Spike Protein

2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Wilson J ◽  
◽  
Sokolova V ◽  
Ji H F ◽  
◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Docking Studies ◽  
Binding Affinities ◽  
S Protein ◽  
Preventative Measures ◽  
Global Pandemic ◽  
Production And Distribution ◽  
In Silico Molecular Docking ◽  
Silico Analysis

March 2020 marked the beginning of a global pandemic caused by SARSCoV- 2. With the development, production and distribution of several vaccines there are hopes to an end in sight. However, with the emergence of several mutated viral strains concerns are mounting as to the effectiveness of the current treatments and preventative measures against the new strains. Herein we analyzed and compared the interaction of the SARS-CoV-2 Spike (S) protein and its variants with human Angiotensin Converting Enzyme (ACE-2) and the binding affinities of several possible S-protein inhibitors with these variants via in silico molecular docking studies. The binding affinities of all the variants to ACE- 2 are less than that of SARS-CoV-2, indicating they are less potent than SARSCoV- 2. The inhibitors, however, showed decreased binding affinity to most of the mutant S-proteins than SARS-CoV-2, indicating it is more difficult to treat COVID using the therapeutic approach targeting the S-protein.

Molecular Docking Studies of Indolyl-Benzodioxyl-Chalcone, Pyrrolyl-Benzodioxyl- Chalcone, and Thiophenyl-Benzodioxyl-Chalcone as an Antimalarial Agent

2021 ◽  
Vol 874 ◽  
pp. 136-142
Author(s):  
Kamilia Mustikasari ◽  
Joshua Eka Harap ◽  
Tanto Budi Susilo ◽  
Noer Komari
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Docking Studies ◽  
Kcal Mole ◽  
Docking Simulations ◽  
Drug Candidates ◽  
Hydrogen Bond Interactions ◽  
New Compounds ◽  
Native Ligand

The drug resistance condition of P. falciparum pose a major challenge in the fight against malaria. This prompts a comprehensive research in an effort to discover new drug candidates. Therefore, chalcone was modified into 24 new compounds, including indolyl-benzodioxyl-chalcone, pyrrolyl-benzodioxyl-chalcone, and thiophenyl-benzodioxyl-chalcone in the course of this study. Moreover, these compounds are commercial malaria mediciations screened for their inhibitory activity using molecular docking simulations. Subsequent results of combined indolyl-benzodioxyl-chalcone and PfDHFR-TS showed the intrinsic indolyl components produced stronger interactions referenced to pyrrolyl-benzodioxyl-chalcone, thiophenyl-benzodioxyl-chalcone, and chloroguanide. Under these circumstances, intense PfDHFR-TS-indolyl-benzodioxyl-chalcone complex was produced with lower binding affinity values (-7.32 to -8.43 kcal/mole) referenced to PfDHFR-TS-pyrrolyl-benzodioxyl-chalcone (-6.38 to -6.68 kcal/mole), PfDHFR-TS-Thiophenyl-benzodioxyl-chalcone (-6.47 to -6.52 kcal/mole), and PfDHFR-TS-chloroguanide (-6.75 kcal/mole). Furthermore, the hydrogen bond interactions developed by indolyl-benzodioxyl-chalcone (7-10) are observably similar to standard chloroguanide compounds and WR99210. These compounds also possess a binding affinity similar to WR99210 (native ligand) and are expected to be potentially anti-malarial candidates.

Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies

2020 ◽  
Vol 20 (3) ◽  
pp. 223-235
Author(s):  
Pooja Shah ◽  
Vishal Chavda ◽  
Snehal Patel ◽  
Shraddha Bhadada ◽  
Ghulam Md. Ashraf
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Reductase Activity ◽  
Infarct Volume ◽  
Docking Studies ◽  
Serum Glucose ◽  
In Vivo Studies ◽  
In Silico Molecular Docking

Background: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. Objective: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. Material and Methods: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. Results: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. Conclusion: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

Molecular docking studies of tea (Thea sinensis Linn.) polyphenols inhibition pattern with Rat P-glycoprotein

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Babar Ali ◽  
Qazi Mohammad Sajid Jamal ◽  
Showkat R. Mir ◽  
Saiba Shams ◽  
Mohammad Amjad Kamal
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Oral Administration ◽  
Docking Studies ◽  
Vital Role ◽  
Glycoprotein P ◽  
High Affinity ◽  
P Glycoprotein ◽  
Inhibition Pattern

AbstractSince 3000 B.C., evergreen plant Thea sinensis (Theaceae) is used both as a social and medicinal beverage. Leaves of T. sinensis contain amino acids, vitamins, caffeine, polysaccharides and polyphenols. Most of the natural medicinal actions of tea are due to the availability and abundance of polyphenols mainly catechins. It has also been stated that some catechins were absorbed more rapidly than other compounds after the oral administration of tea and could increase the bio-enhancing activities of anticancer drugs by inhibiting P-glycoprotein (P-gp). The results of the molecular docking showed that polyphenols bind easily to the active P-gp site. All compounds exhibited fluctuating binding affinity ranged from −11.67 to −8.36 kcal/mol. Observed binding energy required for theaflavin to bind to P-gp was lowest (−11.67 kcal/mol). The obtained data that supports all the selected polyphenols inhibited P-gp and therefore may enhance the bioavailability of drugs. This study may play a vital role in finding hotspots in P-gp and eventually may be proved useful in designing compounds with high affinity and specificity to the protein.

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