scholarly journals Medicinal Plants Against Coronavirus (SARS-COV-2) in Morocco Via Computational Virtual Screening Approach

2021 ◽  
Author(s):  
Mohamed CHEBAIBI ◽  
Dalila Bousta ◽  
Rene Francisco Boschi Gonçalves ◽  
Hasnae Hoummani ◽  
Sanae Achour
Keyword(s):  
Medicinal Plants ◽  
Force Field ◽  
Binding Affinity ◽  
Inhibitory Effect ◽  
Citrus Limon ◽  
Organosulfur Compounds ◽  
Syzygium Aromaticum ◽  
Frequent Use ◽  
Main Protease ◽  
Dynamics Simulations

Abstract With the spread of the coronavirus in all countries of the world and in the absence of a vaccine or effective treatment to inhibit the infection. Several medicinal plants are used by the Moroccan population either to treat or prevent infection. The frequent use of its plants without documentation of their effectiveness on the Covid-19 is justified by cultural and economic reasons and their pharmacological activity scientifically proven. The objective of this study is to evaluate the inhibitory effect of the main polyphenols and flavonoids of Syzygium aromaticum and citrus limon as well as the main organosulfur compounds of garlic against coronavirus 6lu7 protease and 6y2e protease using in-silico molecular docking analysis.The COVID-19 3CLpro/Mpro (PDB ID: 6LU7) and free enzyme of the SARS-CoV-2 (2019- nCoV) main protease (PBD ID: 6Y2E) structures were obtained from the https://www.rcsb.org/ website in .PDB format. The COVID-19 3CLpro/Mpro (PDB ID: 6LU7) and main protease (PBD ID: 6Y2E) were prepared using autodock tools from MGL Tools package http://mgltools.scripps.edu/. The reactive molecular dynamics simulations were performed using the software LAMMPS and the ReaxFF force field. In this force field, the general energy functionWe have docked 34 natural products belonging to the three medicinal plants. In 6LU7 protease, 24 compounds exhibited a binding affinity greater than or equal to -6 Kcal/mol. While, in 6Y2E protease, 6 compounds exhibited a binding affinity greater than or equal to -6 Kcal/mol.We found that ellagic acid, narirutin, neoeriocitrin and neohesperidin are highly suggested as an inhibitor of SARS-COV-2.

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 The impact of curcumin derived polyphenols on the structure and flexibility COVID-19 main protease binding pocket: a molecular dynamics simulation study

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11590
Author(s):  
Aweke Mulu ◽  
Mulugeta Gajaa ◽  
Haregewoin Bezu Woldekidan ◽  
Jerusalem Fekadu W/mariam
Keyword(s):  
Molecular Dynamics ◽  
Binding Affinity ◽  
Binding Pocket ◽  
Dynamics Simulation ◽  
World Health ◽  
Main Protease ◽  
Health Organization ◽  
Dynamics Simulations ◽  
Simulation Parameters ◽  
The Impact

The newly occurred SARS-CoV-2 caused a leading pandemic of coronavirus disease (COVID-19). Up to now it has infected more than one hundred sixty million and killed more than three million people according to 14 May 2021 World Health Organization report. So far, different types of studies have been conducted to develop an anti-viral drug for COVID-19 with no success yet. As part of this, silico were studied to discover and introduce COVID-19 antiviral drugs and results showed that protease inhibitors could be very effective in controlling. This study aims to investigate the binding affinity of three curcumin derived polyphenols against COVID-19 the main protease (Mpro), binding pocket, and identification of important residues for interaction. In this study, molecular modeling, auto-dock coupled with molecular dynamics simulations were performed to analyze the conformational, and stability of COVID-19 binding pocket with diferuloylmethane, demethoxycurcumin, and bisdemethoxycurcumin. All three compounds have shown binding affinity −39, −89 and −169.7, respectively. Demethoxycurcumin and bisdemethoxycurcumin showed an optimum binding affinity with target molecule and these could be one of potential ligands for COVID-19 therapy. And also, COVID-19 main protease binding pocket binds with the interface region by one hydrogen bond. Moreover, the MD simulation parameters indicated that demethoxycurcumin and bisdemethoxycurcumin were stable during the simulation run. These findings can be used as a baseline to develop therapeutics with curcumin derived polyphenols against COVID-19.

scholarly journals Computational Study on Novel Natural Inhibitors Targeting c-MET

2021 ◽  
Author(s):  
Junliang Ge ◽  
Bo Wu ◽  
Wenzhuo Yang ◽  
Sheng Zhong ◽  
Yuanyuan Hou ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Binding Affinity ◽  
Computational Study ◽  
Developmental Toxicity ◽  
Inhibitory Effect ◽  
Dynamics Simulation ◽  
Drug Candidates ◽  
Zinc Database ◽  
The Stability ◽  
Dynamics Simulations

Abstract Object This study was designed to select ideal lead compounds and preclinical drug candidates with inhibitory effect on c-MET from the drug library (ZINC database).Methods A battery of computer-aided virtual techniques were used to identify possible inhibitors of c-MET. LibDock is applied for structure-based screening followed by ADME (absorption, distribution, metabolic, excretion) and toxicity prediction. Molecular docking was conducted to confirm the binding affinity mechanism between the ligand and c-MET Molecular dynamics simulations were used to assess the stability of ligand-c-MET complexes.Results Two new natural compounds ZINC000005879645 and ZINC000002528509 were found to bind to c-MET in ZINC database, showing higher binding affinity. In addition, they were predicted to have lower rodent carcinogenicity, Ames mutagenicity, developmental toxicity potential, and high tolerance to cytochrome P4502D6. Molecular dynamics simulation shows that ZINC000005879645 and ZINC000002528509 have more favorable potential energies with c-MET, which could exist stably in the natural environment.Conclusion This study suggests that ZINC000005879645 and ZINC000002528509 are ideal latent inhibitors of c-MET targeting. As drug candidates, these two compounds have great security and important implications for the design and improvement of c-MET target drugs.

scholarly journals Investigating Potential Inhibitory Effect of Uncaria tomentosa (Cat’s Claw) against the Main Protease 3CLpro of SARS-CoV-2 by Molecular Modeling

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Andres F. Yepes-Pérez ◽  
Oscar Herrera-Calderon ◽  
José-Emilio Sánchez-Aparicio ◽  
Laura Tiessler-Sala ◽  
Jean-Didier Maréchal ◽  
...  
Keyword(s):  
In Silico ◽  
Computational Study ◽  
Inhibitory Effect ◽  
Ligand Docking ◽  
Therapeutic Effects ◽  
Uncaria Tomentosa ◽  
Synthetic Inhibitor ◽  
Main Protease ◽  
Dynamics Simulations ◽  
Free Energy Of Binding

COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2. Presently, there is no effective treatment for COVID-19. As part of the worldwide efforts to find efficient therapies and preventions, it has been reported the crystalline structure of the SARS-CoV-2 main protease Mpro (also called 3CLpro) bound to a synthetic inhibitor, which represents a major druggable target. The druggability of Mpro could be used for discovering drugs to treat COVID-19. A multilevel computational study was carried out to evaluate the potential antiviral properties of the components of the medicinal herb Uncaria tomentosa (Cat’s claw), focusing on the inhibition of Mpro. The in silico approach starts with protein-ligand docking of 26 Cat’s claw key components, followed by ligand pathway calculations, molecular dynamics simulations, and MM-GBSA calculation of the free energy of binding for the best docked candidates. The structural bioinformatics approaches led to identification of three bioactive compounds of Uncaria tomentosa (speciophylline, cadambine, and proanthocyanidin B2) with potential therapeutic effects by strong interaction with 3CLpro. Additionally, in silico drug-likeness indices for these components were calculated and showed good predicted therapeutic profiles of these phytochemicals. Our findings suggest the potential effectiveness of Cat’s claw as complementary and/or alternative medicine for COVID-19 treatment.

scholarly journals Investigating Potential Inhibitory Effect of Uncaria tomentosa (Cat's claw) against the Main Protease 3CLPro of SARS-CoV-2 by Molecular Modeling

2020 ◽  
Author(s):  
Andres F. Yepes-Pérez ◽  
Oscar Herrera-Calderon ◽  
José-Emilio Sánchez-Aparicio ◽  
Laura Tiessler-Sala ◽  
Jean-Didier Maréchal ◽  
...  
Keyword(s):  
In Silico ◽  
Computational Study ◽  
Inhibitory Effect ◽  
Ligand Docking ◽  
Therapeutic Effects ◽  
Uncaria Tomentosa ◽  
Main Protease ◽  
Multi Level ◽  
Dynamics Simulations ◽  
Free Energy Of Binding

COVID-19 is a novel severe acute respiratory syndrome coronavirus. Presently, there is no effective treatment for COVID-19. As part of the worldwide efforts to find efficient therapies and preventions, it has been reported the crystalline structure of the SARS-CoV-2 main protease Mpro (also called 3CLpro) bound to a synthetic inhibitor which represents a major druggable target. The druggability of Mpro could be used for discovering drugs to treat coronavirus disease 2019. It was carried out a multi-level computational study to evaluate the potential anti-viral properties of the components of the medicinal herb Uncaria tomentosa (Cat´s claw) focusing on the inhibition of Mpro. The in-silico approach starts with protein-ligand docking of 26 Cat’s claw key components followed by ligand pathway calculations, molecular dynamics simulations and MM-GBSA calculation of the free energy of binding for the best docked candidates. The structural bioinformatics approaches led to the identification of three bioactive compounds of Uncaria tomentosa (Speciophylline, Cadambine and Proanthocyanidin B2) with potential therapeutic effects by strong interaction with 3CLpro. Additionally, in silico drug-likeness indices for these components were calculated and show good predicted therapeutic profiles of these phytochemicals. Our findings suggest the potential effectiveness of Cat's claw as complementary and/or alternative medicine for COVID-19 treatment.

scholarly journals Molekuler Docking tehadap Senyawa Eugenol dan Myricetin pada Tanaman Cengkeh (Syzygium aromaticum) sebagai Penghambat Pertumbuhan SARS-CoV-2

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Yizreel Y. Gerungan ◽  
Billy J. Kepel ◽  
. Fatimawali ◽  
Aaltje Manampiring ◽  
Fona D. Budiarso ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Growth Inhibitor ◽  
Syzygium Aromaticum ◽  
Amino Acid Residues ◽  
Autodock Vina ◽  
Discovery Studio ◽  
Main Protease ◽  
Almost All ◽  
The Impact

Abstract: Cloves contain many chemical compounds that can be used for health. COVID-19 is a disease that is shaking the world today. Many people feel the impact of this disease. Until now, there is no definite cure and vaccine for the handling of COVID-19.  Objective to determine the interaction between compounds in cloves (eugenol and myricetin) and the main protease COVID-19 (6LU7). This study use a molecular docking, method using 4 main applications: autodock tools, autodock vina, biovia discovery studio and open babel. This study showed that almost all amino acid residues in the eugenol and myricetin compounds worked on the 6LU7 active site. The binding affinity of eugenol compounds in clove plants does not exceed the binding affinity of remdesivir, a drug studied as a drug for handling COVID-19, while the binding affinity of myricetin compounds in cloves plant exceeds the binding affinity of remdesivir. In conclusion, myricetin compounds have better results for use as a growth inhibitor for COVID-19 than eugenol.Key words: Cloves, COVID-19, molecular docking.  Abstrak: Cengkeh memiliki banyak kandungan senyawa kimia yang dapat dimanfaatkan bagi kesehatan. COVID-19 merupakan penyakit yang mengguncang dunia saat ini. Banyak masyarakat yang merasakan dampak dari penyakit ini. Hingga saat ini belum ada obat dan vaksin yang pasti untuk penanganan COVID-19. Penelitian ini bertujuan untuk mengetahui interaksi antara senyawa pada cengkeh (eugenol dan myricetin) dengan main protease COVID-19 (6LU7). Jenis penelitian ini menggunakan metode molekuler docking dengan menggunakan 4 aplikasi utama: autodock tools, autodock vina, biovia discovery studio dan open babel. Hasil penelitian ini menunjukkan bahwa hampir semua residu asam amino pada senyawa eugenol dan myricetin bekerja pada sisi aktif 6LU7. Hasil binding affinity senyawa eugenol pada tumbuhan cengkeh tidak melebihi binding affinity dari remdesivir, obat yang diteliti sebagai obat penanganan COVID-19, sedangkan hasil binding affinity senyawa myricetin pada tumbuhan cengkeh melebihi binding affinity dari remdesivir. Simpulan penelitian ini ialah senyawa myricetin memiliki hasil yang lebih baik untuk digunakan sebagai penghambat pertumbuhan COVID-19 dari pada eugenol.Kata kunci: Cengkeh, COVID-19, molekuler docking.

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 Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Vicky Mody ◽  
Joanna Ho ◽  
Savannah Wills ◽  
Ahmed Mawri ◽  
Latasha Lawson ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Inhibitory Effects ◽  
Major Threat ◽  
Main Protease ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Computational Molecular Modeling

AbstractEmerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets.

scholarly journals The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 873
Author(s):  
Raphael J. Eberle ◽  
Danilo S. Olivier ◽  
Marcos S. Amaral ◽  
Ian Gering ◽  
Dieter Willbold ◽  
...  
Keyword(s):  
Binding Mode ◽  
Drug Candidates ◽  
Main Protease ◽  
Ic50 Values ◽  
Repurposed Drugs ◽  
Antiparasitic Drugs ◽  
Inhibitory Potential ◽  
Dynamics Simulations ◽  
Micromolar Range

Since the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude. To date, several clinically safe and efficient vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs for emergency use have been approved. However, increasing numbers of SARS-Cov-2 variants make it imminent to identify an alternative way to treat SARS-CoV-2 infections. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is repurposing clinically developed drugs, e.g., antiparasitic drugs. The results described in this study demonstrated the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CLpro). Quinacrine and suramin molecules presented a competitive and noncompetitive inhibition mode, respectively, with IC50 values in the low micromolar range. Surface plasmon resonance (SPR) experiments demonstrated that quinacrine and suramin alone possessed a moderate or weak affinity with SARS-CoV-2 3CLpro but suramin binding increased quinacrine interaction by around a factor of eight. Using docking and molecular dynamics simulations, we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin, in combination with quinacrine, showed promising synergistic efficacy to inhibit SARS-CoV-2 3CLpro. We suppose that the identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease and repurposable drug candidates offer fast therapeutic breakthroughs, mainly in a pandemic moment.

scholarly journals Deciphering the Interactions of Bioactive Compounds in Selected Traditional Medicinal Plants against Alzheimer’s Diseases via Pharmacophore Modeling, Auto-QSAR, and Molecular Docking Approaches

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1996
Author(s):  
 Oluwafemi Adeleke Ojo ◽  
Adebola Busola Ojo ◽  
Charles Okolie ◽  
Mary-Ann Chinyere Nwakama ◽  
Matthew Iyobhebhe ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Receiver Operating Characteristic ◽  
Binding Affinity ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Screening Method ◽  
Pharmacophore Modeling ◽  
Structure Identification ◽  
Mao Activity ◽  
Receiver Operating

Neurodegenerative diseases, for example Alzheimer’s, are perceived as driven by hereditary, cellular, and multifaceted biochemical actions. Numerous plant products, for example flavonoids, are documented in studies for having the ability to pass the blood-brain barrier and moderate the development of such illnesses. Computer-aided drug design (CADD) has achieved importance in the drug discovery world; innovative developments in the aspects of structure identification and characterization, bio-computational science, and molecular biology have added to the preparation of new medications towards these ailments. In this study we evaluated nine flavonoid compounds identified from three medicinal plants, namely T. diversifolia, B. sapida, and I. gabonensis for their inhibitory role on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidase (MAO) activity, using pharmacophore modeling, auto-QSAR prediction, and molecular studies, in comparison with standard drugs. The results indicated that the pharmacophore models produced from structures of AChE, BChE and MAO could identify the active compounds, with a recuperation rate of the actives found near 100% in the complete ranked decoy database. Moreso, the robustness of the virtual screening method was accessed by well-established methods including enrichment factor (EF), receiver operating characteristic curve (ROC), Boltzmann-enhanced discrimination of receiver operating characteristic (BEDROC), and area under accumulation curve (AUAC). Most notably, the compounds’ pIC50 values were predicted by a machine learning-based model generated by the AutoQSAR algorithm. The generated model was validated to affirm its predictive model. The best models achieved for AChE, BChE and MAO were models kpls_radial_17 (R2 = 0.86 and Q2 = 0.73), pls_38 (R2 = 0.77 and Q2 = 0.72), kpls_desc_44 (R2 = 0.81 and Q2 = 0.81) and these externally validated models were utilized to predict the bioactivities of the lead compounds. The binding affinity results of the ligands against the three selected targets revealed that luteolin displayed the highest affinity score of −9.60 kcal/mol, closely followed by apigenin and ellagic acid with docking scores of −9.60 and −9.53 kcal/mol, respectively. The least binding affinity was attained by gallic acid (−6.30 kcal/mol). The docking scores of our standards were −10.40 and −7.93 kcal/mol for donepezil and galanthamine, respectively. The toxicity prediction revealed that none of the flavonoids presented toxicity and they all had good absorption parameters for the analyzed targets. Hence, these compounds can be considered as likely leads for drug improvement against the same.

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