scholarly journals Promising inhibitors against main protease of SARS CoV-2 from medicinal plants: In silico identification

2021 ◽  
Vol 72 (2) ◽  
pp. 159-169
Author(s):  
OLUWAKEMI EBENEZER ◽  
MICHAEL SHAPI
Keyword(s):  
Medicinal Plants ◽  
Binding Affinity ◽  
In Silico ◽  
Complex Analysis ◽  
Docking Studies ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Pharmacokinetic Properties ◽  
Lipinski’S Rule Of Five ◽  
In Silico Identification

Abstract Some compounds reported as active against SARS CoV were selected, and docking studies were performed using the main protease of SARS CoV-2 as the receptor. The docked complex analysis shows that the ligands selectively bind with the target residues and binding affinity of amentoflavone (–10.1 kcal mol–1), isotheaflavin-3’-gallate (–9.8 kcal mol–1), tomentin A and D (–8.0 and –8.8 kcal mol–1), theaflavin-3,3’-digallate (–8.6 kcal mol–1), papyriflavonol A (–8.4 kcal mol–1), iguesterin (–8.0 kcal mol–1) and savinin (–8.3 kcal mol–1) were ranked above the binding affinity of the reference, co-crystal ligand, ML188, a furan-2-carboxamide-based compound. To pinpoint the drug-like compound among the top-ranked compounds, the Lipinski’s rule of five and pharmacokinetic properties of all the selected compounds were evaluated. The results detailed that savinin exhibits high gastrointestinal absorption and can penetrate through the blood-brain barrier. Also, modifying these natural scaffolds with excellent binding affinity may lead to discovering of anti-SARS CoV agents with promising safety profiles.

scholarly journals Design of Chalcones of 7-Azaindole as Raf-B Inhibitors

2019 ◽  
Vol 4 (4) ◽  
pp. 606-608 ◽  
Author(s):  
D. Giles ◽  
V.N. Saiprabha ◽  
G. Yeshna
Keyword(s):  
Binding Affinity ◽  
Active Site ◽  
In Silico ◽  
Significant Interaction ◽  
Docking Score ◽  
Lipinski’S Rule ◽  
Lipinski’S Rule Of Five

The present work deals with the design of 7-azaindole derivatives for its Raf-B inhibition. All the designed compounds follows Lipinski’s rule of five. In silico ADME predictions of all the designed compounds suggests that none of the compounds have problem with bioavailability. The compounds were designed on the binding affinity towards the Raf-B inhibition. It was observed that few of the designed compounds were found to have significant interaction with the active site of the receptor. The compounds possessing 3-hydroxyl-2-methyl as substitution in chalcone was found to possess maximum docking score than other designed compounds.

In silico insight into the inhibitory effects of active antidiabetic compounds from medicinal plants against SARS-CoV-2 replication and posttranslational modification

Coronaviruses ◽  
2021 ◽  
Vol 02 ◽  
Author(s):  
Habibu Tijjani ◽  
Adamu Idris Matinja ◽  
Ahmed Olatunde ◽  
Maryam Haladu Zangoma ◽  
Abubakar Mohammed ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
In Silico ◽  
Experimental Studies ◽  
Inhibitory Effects ◽  
Post Translational Modifications ◽  
Lipinski’S Rule ◽  
In Silico Studies ◽  
Lipinski’S Rule Of Five ◽  
Mutation Assay ◽  
Insight Into

Background: The recent reemergence of the coronavirus (COVID-19) caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has prompted for the search of effective treatments in forms of drugs and vaccines. Aim: In this regards, we performed an in silico studies of 39 active antidiabetic compounds from medicinal plants to provide insight into their possible inhibitory potentials against SARS-CoV-2 replications and post-translational modifications. Top 12 active antidiabetic compounds with potential for dual inhibition of the replications and post-translational modifications of SARS-CoV-2 were analyzed. Results: Boswellic acids, celastrol, rutin, sanguinarine, silymarin and withanolides expressed binding energy for 3- chymotrypsin-like protease (3CLpro) (-8.0 to -8.9 Kcal/mol), papain-like protease (PLpro) (-9.1 to -10.2 Kcal/mol) and RNA-dependent RNA polymerase (RdRp) (-8.5 to -9.1 Kcal/mol) which were higher than that of the reference drugs (Lopinavir and Remdesivir) used in this study. Sanguinarine, silymarin and withanolides are most drugable phytochemicals among the other following phytochemicals as they obey the Lipinski’s rule of five analyses. Sanguinarine, silymarin and withanolides express moderately soluble with no hepatotoxicity, while silymarin and withanolides cannot permeate the blood-brain barrier and showed no Salmonella typhimurium reverse mutation assay (AMES) toxicity, unlike sanguinarine from the predictive absorption, distribution, metabolism, elimination, and toxicity (ADMET) studies. Conclusion: Sanguinarine, silymarin and withanolides could be proposed for further experimental studies for their development as possible phytotherapy for the COVID-19 pandemic.

scholarly journals Computational analysis by molecular docking of thirty alkaloid compounds from medicinal plants as potent inhibitors of SARS-CoV-2 main protease

2021 ◽  
Vol 4 (4) ◽  
pp. 487-503
Author(s):  
Tunga Kuhana A ◽  
◽  
Jason T. Kilembe ◽  
Aristote Matondo ◽  
Khamis M. Yussuf ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Medicinal Plants ◽  
Computational Analysis ◽  
Potential Drug ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Potential Inhibitors ◽  
Therapeutic Profile

Year 2020 has been highly affected by the COVID-19 outbreak. The urgent need for a potent and effective drug for the treatment of this malignancy put pressure on researchers and scientists worldwide to develop a potential drug or a vaccine to resist SARS-CoV-2 virus. We report in this paper the assessment of the efficiency of thirty alkaloid compounds derived from African medicinal plants against the SARS-CoV-2 main protease through molecular docking and bioinformatics approaches. The results revealed four potential inhibitors (ligands 18, 21, 23 and 24) with 12.26 kcal/mol being the highest binding energy. Additionally, in silico drug-likeness and ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) properties for the four ligands showed a good predicted therapeutic profile of druggability, and fully obey the Lipinski's rule of five as well.

Novel 7-substituted Fluoroquinolone Citrate Conjugates as Powerful Antibacterial and Anticancer Agents: Synthesis and Molecular Docking Studies

2019 ◽  
Vol 23 (18) ◽  
pp. 1992-2003
Author(s):  
Tejeswara R. Allaka ◽  
Jaya S. Anireddy
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Line ◽  
Anticancer Agents ◽  
Docking Studies ◽  
Significant Activity ◽  
Anticancer Activities ◽  
Lipinski’S Rule ◽  
Ic50 Value ◽  
Pharmacokinetic Properties ◽  
Lipinski’S Rule Of Five

In this study, the synthesis and evaluation of norfloxacin analogues of dimethyl citrate conjugates were described and their antibacterial and anticancer activities were assessed. The cognate 7-substituted norfloxacin citrate conjugates are active against various strains of bacteria, including MRSA (methicillin-resistant Staphylococcus aureus) with higher activity than ciprofloxacin. Screening results indicated that compound 10 possessed good antibacterial activity against several microorganisms, with MIC values in the range of 0.16-0.35 mg/mL and MBCs in the range of 0.55-0.84 mg/mL. Experiments indicated that 9 demonstrated the most significant activity towards the HCT-15 cell line with IC50 value 8.2 ± 0.139 and against the HT-29 cell line with IC50 8.9 ± 0.122. The title compounds were also evaluated for determining the molecular and pharmacokinetic properties and drug-likeness model scores by using the Molinspiration-2008 and MolSoft-2007 softwares. The region isomeric conjugates followed the Lipinski’s rule of five can be considered as potential antibacterial and anticancer bioavailable oral leads. Compounds 9 and 10 possessed maximum drug-likeness scores. The docking pose interactions of target compounds with the active site of enzyme PDB: 2ZCS of Staphylococcus aureus were estimated by using Autodock 4.2, to calculate the affinity, binding orientation of the ligand with the target protein and to explore the finest conformations. The target compounds, 7, 8, 9, 10, with protein, were loaded separately into Auto dock tools (ADT) and evaluated. The citrate conjugates, 8, 9, showed better docking scores with amino acids Lys17, Ser21, Val268, Lys273 and Arg171, Arg265, Val268, Val273 with the binding energy -5.70, -5.57 kcal/mol and dissociation constant 66.62, 82.13 µM respectively.

scholarly journals Computational analysis by molecular docking of thirty alkaloid compounds from medicinal plants as potent inhibitors of SARS-CoV-2 main protease

2020 ◽  
Author(s):  
Tunga Kuhana A. ◽  
Jason T. Kilembe ◽  
Aristote Matondo ◽  
Khamis M. Yussuf ◽  
Lauraine Nininahazwe ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Medicinal Plants ◽  
Computational Analysis ◽  
Binding Energies ◽  
Effective Drug ◽  
Potential Drug ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Potential Inhibitors

Abstract 2020 has been highly affected by the COVID-19 outbreak. The urgent needs for a potent and effective drug for treatment of this malignance put pressure on researchers and scientists worldwide to develop potential drug or a vaccine to resist SARS-CoV-2. We report in this paper the assessment of the efficiency of thirty alkaloid compounds derived from African medicinal plants against the SARS-CoV-2 main protease through molecular docking and bioinformatics approaches. The results reveal four potential inhibitors (ligands 18, 21, 23 and 24) with the highest binding energies up to 12.26 kcal/mol with good profile of ADMET, as well as fully obey the Lipinski’s rule of five.

Discovery of Some Antiviral Natural products to fight against Novel Corona Virus (SARS-CoV-2) using Insilico approach

2020 ◽  
Vol 23 ◽  
Author(s):  
Ashish Shah ◽  
Vaishali Patel ◽  
Bhumika Parmar
Keyword(s):  
Binding Affinity ◽  
Protein S ◽  
Docking Studies ◽  
Spike Protein ◽  
Enveloped Viruses ◽  
Bioactivity Prediction ◽  
Corona Virus ◽  
Main Protease ◽  
Antiviral Activities ◽  
Deadly Disease

Background: Novel Corona virus is a type of enveloped viruses with a single stranded RNA enclosing helical nucleocapsid. The envelope consists of spikes on the surface which are made up of proteins through which virus enters into human cells. Until now there is no specific drug or vaccine available to treat COVID-19 infection. In this scenario, reposting of drug or active molecules may provide rapid solution to fight against this deadly disease. Objective: We had selected 30 phytoconstituents from the different plants which are reported for antiviral activities against corona virus (CoVs) and performed insilico screening to find out phytoconstituents which have potency to inhibit specific target of novel corona virus. Methods: We had perform molecular docking studies on three different proteins of novel corona virus namely COVID-19 main protease (3CL pro), papain-like protease (PL pro) and spike protein (S) attached to ACE2 binding domain. The screening of the phytoconstituents on the basis of binding affinity compared to standard drugs. The validations of screened compounds were done using ADMET and bioactivity prediction. Results: We had screened five compounds biscoclaurine, norreticuline, amentoflavone, licoricidin and myricetin using insilico approach. All compounds found safe in insilico toxicity studies. Bioactivity prediction reviles that these all compounds may act through protease or enzyme inhibition. Results of compound biscoclaurine norreticuline were more interesting as this biscoclaurine had higher binding affinity for the target 3CLpro and PLpro targets and norreticuline had higher binding affinity for the target PLpro and Spike protein. Conclusion: Our study concludes that these compounds could be further explored rapidly as it may have potential to fight against COVID-19.

scholarly journals Molecular Docking Studies of Flavonoids from Andrographis paniculata as Potential Acetylcholinesterase, Butyrylcholinesterase and Monoamine Oxidase Inhibitors Towards the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 11 (3) ◽  
pp. 9871-9879
Keyword(s):  
Molecular Docking ◽  
Monoamine Oxidase ◽  
Neurodegenerative Diseases ◽  
Docking Studies ◽  
Monoamine Oxidase Inhibitors ◽  
Andrographis Paniculata ◽  
Lipinski’S Rule ◽  
Bioinformatic Tools ◽  
Pubchem Database ◽  
Lipinski’S Rule Of Five

Neurodegenerative diseases have been characterized by loss of neuron structures as well as their functions. This study was designed to assess molecular docking of flavonoids from Andrographis paniculata as potential acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase inhibitors in the treatment of neurodegenerative diseases. Eight identified possible inhibitors of acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase from Andrographis paniculata were retrieved from the PubChem database. The molecular docking, ADMET, and Lipinski’s rule of five were examined using different bioinformatic tools. It was shown that only rutin has the highest binding affinity (-12.6 kcal/mol) than the standard used. ADMET results demonstrated that all the eight compounds are druggable candidates except rutin. Also, only tangeritin has a blood-brain barrier (BBB) permeation potential. Hence, it can be deduced that all flavonoid compounds from Andrographis paniculata are orally druggable, which can make them useful in the treatment of neurodegenerative diseases better than donepezil.

scholarly journals AN IN SILICO STUDY OF NARINGENIN-MEDIATED NEUROPROTECTION IN PARKINSON’S DISEASE

2017 ◽  
Vol 10 (8) ◽  
pp. 171
Author(s):  
Saurabh Kumar Jha ◽  
Pravir Kumar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
In Silico ◽  
E3 Ligase ◽  
Docking Studies ◽  
Dimensional Structure ◽  
Molecular Docking Studies ◽  
Lipinski’S Rule ◽  
Ubiquitin E3 Ligase

  Objective: Naringenin is a dietary biomolecule with broad spectrum of activities which protects neurons from various neurotoxic insults and improves cognition and motor function in neurodegenerative diseases. DJ-1 has both, ubiquitin E3 ligase as well as chaperonic activity, and loss of ubiquitin E3 ligase activity of DJ-1 has been found to be associated with familial Parkinson’s disease (PD). Naringenin induced E3 ligase activity of DJ-1 which can have possible clinical relevance in PD.Methods: Various in silico parameters such as phylogenetic analysis, homology modeling, active site prediction, and molecular docking studies using AutoDock 4.2.1 and LIGPLOT1.4.5 were carried out.Results: Three-dimensional structure of DJ-1 was generated and Ramachandran plot was obtained for quality assessment. RAMPAGE displayed 99.5% of residues in the most favored regions. 0% residues in additionally allowed and 0.5% disallowed regions of DJ-1 protein. Further, initial screenings of the molecules were done based on Lipinski’s rule of five. CastP server used to predict the ligand binding site suggests that this protein can be utilized as a potential drug target. Finally, we have found naringenin to be most effective among four biomolecules in modulating DJ-1 based on minimum inhibition constant, Ki, and highest negative free energy of binding with maximum interacting surface area in the course of docking studies.Conclusion: Our study suggests that based on different in silico parameters and molecular docking studies, naringenin can provide a new avenue for PD therapeutics.

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