MOLECULAR DOCKING STUDY OF NATURALLY OCCURRING COMPOUNDS AS INHIBITORS OF COVID -19

This study aimed to determine the activity of PYT and its derivatives against COX-2, including 5IKR protein induced inflammation by using the computational tools. PYT and its derivatives have been designed by utilizing density functional theory (DFT) and the performance of the drugs was also evaluated by molecular docking study. Results suggest that the NH2 derivative of PYT (D-NH2) showed binding energy -6.4 (Kcal/mol) with protein 5IKR of COX-2 compared to the main drug (D) that showed binding energy -5.1 (Kcal/mol) with the same protein. HOMO and LUMO energy values were also calculated to determine the chemical reactivity of all the modified drugs. Non-covalent interactions of PYT and its derivatives were essential in improving the performance. In conclusion, D-NH2 showed better preference in inhibiting to the protein 5IKR of COX-2 compared to other modified drugs and it can be claimed that D-NH2 will be the best conformer for COX-2 induced inflammation.

Download Full-text

MOLECULAR DOCKING STUDY TO IDENTIFY POTENTIAL INHIBITOR OF COVID-19 MAIN PROTEASE ENZYME: AN IN-SILICO APPROACH

10.26434/chemrxiv.12170904 ◽

2020 ◽

Author(s):

Anurag Agrawal ◽

Nem Kumar Jain ◽

Neeraj Kumar ◽

Giriraj T Kulkarni

Keyword(s):

Molecular Docking ◽

Active Site ◽

Docking Study ◽

Molecular Docking Study ◽

Potential Threat ◽

Discovery Studio ◽

Chemical Structures ◽

Potential Inhibitor ◽

Protease Enzyme ◽

Main Protease

This study belongs to identification of suitable COVID-19 inhibitors <div> </div><div>Coronavirus became pandemic very soon and is a potential threat to human lives across the globe. No approved drug is currently available therefore an urgent need has been developed for any antiviral therapy for COVID-19. For the molecular docking study, ten herbal molecules have been included in the current study. The three-dimensional chemical structures of molecules were prepared through ChemSketch 2015 freeware. Molecular docking study was performed using AutoDock 4.2 simulator and Discovery studio 4.5 was employed to predict the active site of target enzyme. Result indicated that all-natural molecules found in the active site of enzyme after molecular docking. Oxyacanthine and Hypericin (-10.990 and -9.05 and kcal/mol respectively) have shown good binding efficacy among others but Oxyacanthine was the only natural product which made some of necessary interactions with residues in the enzyme require for target inhibition. Therefore Oxyacanthine may be considered to be potential inhibitor of main protease enzyme of virus but need to be explored for further drug development process. </div>

Download Full-text

Novel Structural Mechanism of Glutathione as a Potential Peptide Inhibitor to the Main Protease (Mpro): CoviD-19 Treatment, Molecular Docking and SAR Study

10.26434/chemrxiv.12153021 ◽

2020 ◽

Author(s):

abde lina ◽

Khedidja BENAROUS ◽

Mohamed Yousfi

Keyword(s):

Molecular Docking ◽

Pantothenic Acid ◽

Vitamin B1 ◽

Docking Study ◽

Binding Pocket ◽

Molecular Docking Study ◽

Structural Mechanism ◽

Discovery Studio ◽

Main Protease ◽

Sar Study

2019-nCoV Coronavirus spread all over the world and obliged one billion people in open confinement, no treatments or vaccine have been yet found against this pandemic. The Main Protease (Mpro) is an attractive drug target, because it is the essential protein for the virus invasion. This study aims to test in silico the effect of five vitamins and a natural antioxidant against Mpro, using molecular docking study, with Autodock Vina and Discovery Studio visualizer softwares. The used inhibitors were chosen based on their beneficial properties such as Tocopherol (vitamin E), Thiamine (vitamin B1), Pantothenic acid (vitamin B5), Pyridoxine (vitamin B6), Biotin (vitamin B7), and Glutathione (GSH), the best inhibitor pose was chosen based on the repetition ratio (RR) and the minimum affinity energy value (MEV). The results show that Glutathione is the best inhibitor model among the other tested vitamins in the active site of Mpro with a RR value of 94% and MEV of - 5.5 kcal/mol, the compatibility of Glutathione structure inside the binding pocket as a tripeptide model found to be similar to the native ligand of Mpro. Moreover, Thiamine, Biotin, and Tocopherol are saved as satisfied inhibitors to Mpro, Pyridoxine was the weakest inhibitor. Depending on this result, we recommend the use of Glutathione and vitamin B family as a supportive strategy for the treatment of COVID-19.

Download Full-text

Novel Structural Mechanism of Glutathione as a Potential Peptide Inhibitor to the Main Protease (Mpro): CoviD-19 Treatment, Molecular Docking and SAR Study

10.26434/chemrxiv.12153021.v1 ◽

2020 ◽

Author(s):

abde lina ◽

Khedidja BENAROUS ◽

Mohamed Yousfi

Keyword(s):

Molecular Docking ◽

Pantothenic Acid ◽

Vitamin B1 ◽

Docking Study ◽

Binding Pocket ◽

Molecular Docking Study ◽

Structural Mechanism ◽

Discovery Studio ◽

Main Protease ◽

Sar Study

2019-nCoV Coronavirus spread all over the world and obliged one billion people in open confinement, no treatments or vaccine have been yet found against this pandemic. The Main Protease (Mpro) is an attractive drug target, because it is the essential protein for the virus invasion. This study aims to test in silico the effect of five vitamins and a natural antioxidant against Mpro, using molecular docking study, with Autodock Vina and Discovery Studio visualizer softwares. The used inhibitors were chosen based on their beneficial properties such as Tocopherol (vitamin E), Thiamine (vitamin B1), Pantothenic acid (vitamin B5), Pyridoxine (vitamin B6), Biotin (vitamin B7), and Glutathione (GSH), the best inhibitor pose was chosen based on the repetition ratio (RR) and the minimum affinity energy value (MEV). The results show that Glutathione is the best inhibitor model among the other tested vitamins in the active site of Mpro with a RR value of 94% and MEV of - 5.5 kcal/mol, the compatibility of Glutathione structure inside the binding pocket as a tripeptide model found to be similar to the native ligand of Mpro. Moreover, Thiamine, Biotin, and Tocopherol are saved as satisfied inhibitors to Mpro, Pyridoxine was the weakest inhibitor. Depending on this result, we recommend the use of Glutathione and vitamin B family as a supportive strategy for the treatment of COVID-19.

Download Full-text

Pyridine and Benzoisothiazole Decorated Vanillin Chalcones: Synthesis, Antimicrobial, Antioxidant, Molecular Docking Study and ADMET Properties

Current Organic Synthesis ◽

10.2174/1570179417666200407130122 ◽

2020 ◽

Vol 17 (5) ◽

pp. 367-381

Author(s):

Pintu Pathare ◽

Sunil Tekale ◽

Rafique Shaikh ◽

Manoj Damale ◽

Jaiprakash Sangshetti ◽

...

Keyword(s):

Molecular Docking ◽

Antioxidant Activities ◽

Radical Scavenging ◽

Docking Study ◽

Docking Studies ◽

Pharmacokinetic Parameters ◽

Molecular Docking Study ◽

Antimicrobial Drugs ◽

Discovery Studio ◽

Pharmacokinetic Properties

Background: The search for new antimicrobial drugs is a never ending task due to microbial resistance to the existing drugs. Antioxidants are essential to prevent free radical reactions which lead to chronic diseases to human kind. Objective: The present studies were aimed to synthesis, characterization, antimicrobial and antioxidant activities of pyridine and benzoisothiazole decorated chalcones. Materials and Methods: FTIR spectra were recorded using KBr pellets on Shimadzu FT-IR spectrophotometer. 1H and 13C NMR spectra were recorded on Bruker 400 MHz spectrometer. Antimicrobial activity of the synthesized chalcones was found to be good against diffenet bacterial and fungal strains. Antioxidant activity was studied in terms of 2,2-diphenyl-1-picrylhydrazyl, hydroxyI and superoxide radical scavenging activities. Molecular docking was studied using Discovery Studio Visualizer Software, version 16 whereas Autodock Vina program was used to predict toxicity profile of the compounds using FAFDrugs2 predictor. Results: The compounds 5c, 5d & 6c showed good antioxidant activities. The insilico molecular docking study supports the experimental results and demonstrated that the chalcones 5d, 6a and 7a are the most active among the synthesized derivatives. Conclusion: Prediction of pharmacokinetic parameters and molecular docking studies suggest that the synthesized chalcones have good pharmacokinetic properties to act as lead molecules in the drug discovery process.

Download Full-text

In silico investigation of Alliin as potential activator for AMPA receptor

Biomedical Physics & Engineering Express ◽

10.1088/2057-1976/ac351c ◽

2021 ◽

Author(s):

Hilal Ozturk ◽

N. Yorulmaz ◽

Mustafa Durgun ◽

Harun Basoglu

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Ampa Receptor ◽

Docking Study ◽

Binding Energies ◽

Molecular Docking Study ◽

Gaba A ◽

Docking Method ◽

Ampa And Nmda Receptors ◽

The Central Nervous System

Abstract Natural products from plants, such as flavonoids, arouse immense interest in medicine because of the therapeutic and many other bioactive properties. The molecular docking is a very useful method to screen the molecules based on their free binding energies and give important structural suggestions about how molecules might activate or inhibit the target receptor by comparing reference molecules. Alliin and Allicin differ from many other flavonoids because of containing no benzene rings and having nitrogen and sulfur atoms in their structure. In this study Alliin and Allicin affinity on AMPA, NMDA and GABA-A receptors were evaluated in the central nervous system by using the molecular docking method. Both Alliin and Allicin indicated no inhibitory effects. However Alliin showed significant selectivity to human AMPA receptor (3RN8) as an excitatory. The binding energy of glutamate to 3RN8 was -6.61 kcal/mol, while the binding energy of Allin was -8.08 kcal/mol. Furthermore Alliin’s affinity to the other AMPA and NMDA receptors is quite satisfactory compared to the reference molecule glutamate. In conclusion based on the molecular docking study, Alliin can be useful for synaptic plasticity studies whereas might be enhance seizure activity because of the increased permeability to cations. It also can be beneficial to improve learning and memory and can be used as a supportive product to the hypofunction of NMDA associated problems.

Download Full-text

A Comparative Study of Approved Drugs for SARS-CoV-2 by Molecular Docking

Journal of Molecular Docking ◽

10.33084/jmd.v1i1.2148 ◽

2021 ◽

Vol 1 (1) ◽

pp. 25-31

Author(s):

Achal Mishra ◽

Radhika Waghela

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Docking Studies ◽

Target Protein ◽

Molecular Docking Study ◽

Discovery Studio ◽

Drug Molecules ◽

Main Protease ◽

New Type ◽

Approved Drugs

SARS-CoV-2, a new type of Coronavirus, has affected more millions of people worldwide. From the spread of this infection, many studies related to this virus and drug designing for the treatment have been started. Most of the studies target the SARS-CoV-2 main protease, spike protein of SASR-CoV-2, and some are targeting the human furin protease. In the current work, we chose the clinically used drug molecules remdesivir, favipiravir, lopinavir, hydroxychloroquine, and chloroquine onto the target protein SARS-CoV-2 main protease. Docking studies were performed using Arguslab, while Discovery Studio collected 2D and 3D pose views with the crystal structure of COVID-19 main protease in complex with an inhibitor N3 with PDB ID 6LU7. Computational studies reveal that all ligands provided good binding affinities towards the target protein. Among all the chosen drugs, lopinavir showed the highest docking score of -11.75 kcal/mol. The results from this molecular docking study encourage the use of lopinavir as the first-line treatment drug due to its highest binding affinity.

Download Full-text

Identification of Potent COVID-19 Main Protease (Mpro) Inhibitors from Natural Polyphenols: An in Silico Strategy Unveils a Hope against CORONA

10.20944/preprints202003.0333.v1 ◽

2020 ◽

Cited By ~ 28

Author(s):

Sevki Adem ◽

Volkan Eyupoglu ◽

Iqra Sarfraz ◽

Azhar Rasul ◽

Muhammad Ali

Keyword(s):

Molecular Docking ◽

Drug Target ◽

Docking Study ◽

Binding Energies ◽

Therapeutic Drug ◽

Molecular Docking Study ◽

Molegro Virtual Docker ◽

Main Protease ◽

Chinese Researcher ◽

Native Ligand

COVID-19, a rapidly spreading new strain of coronavirus, has affected more than 150 countries and received worldwide attention. The lack of efficacious drugs or vaccines against SARS-CoV-2 has further worsened the situation. Thus, there is an urgent need to boost up research for the development of effective therapeutics and affordable diagnostic against COVID-19. The crystallized form of SARS-CoV-2 main protease (Mpro) was demonstrated by a Chinese researcher Liu et al. (2020) which is a novel therapeutic drug target. This study was conducted to evaluate the efficacy of medicinal plant-based bioactive compounds against COVID-19 Mpro by molecular docking study. Molecular docking investigations were performed by using Molegro Virtual Docker 7 to analyze the inhibition probability of these compounds against COVID-19. COVID-19 Mpro was docked with 80 flavonoid compounds and the binding energies were obtained from the docking of (PDB ID: 6LU7: Resolution 2.16 Å) with the native ligand. According to obtained results, hesperidin, rutin, diosmin, apiin, diacetylcurcumin, (E)-1-(2-Hydroxy-4-methoxyphenyl)-3-[3-[(E)-3-(2-hydroxy-4- methoxyphenyl)-3-oxoprop-1-enyl]phenyl]prop-2-en-1-one, and beta,beta'-(4-Methoxy-1,3- phenylene)bis(2'-hydroxy-4',6'-dimethoxyacrylophenone have been found as more effective on COVID-19 than nelfinavir. So, this study will pave a way for doing advanced experimental research to evaluate the real medicinal potential of these compounds to cure COVID-19.

Download Full-text

Molecular Docking Study of drug molecules from Drug Bank database against COVID-19 Mpro protein

10.31219/osf.io/cmtk6 ◽

2020 ◽

Cited By ~ 1

Author(s):

Tushar Joshi ◽

Shalini Mathpal ◽

Priyanka Sharma ◽

Tanuja Joshi ◽

Hemlata Pundir ◽

...

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Drug Repurposing ◽

Economic Loss ◽

Docking Study ◽

New Drugs ◽

High Morbidity ◽

Molecular Docking Study ◽

Drug Molecules ◽

Therapeutic Development

Aims: SARS-CoV-2 which is NovelCoronavirushas been disseminated all over the world and causing Coronavirus disease (COVID-19) resulting in many deaths as well as economic loss in several countries.This virus is showinga considerable amount of high morbidity and mortality.Currently, no drugs are available againstSARS-CoV-2. Therefore,for the treatment of disease, researchers are looking fornew drugs that can treat the disease and prevent it to be spread.In this regard,drug repurposingmay help scientists for treating and preventing infections associated with SARS-CoV-2. Drug repurposingis a strategy that can identify new targets for existing drugs that are already approved for the treatment of a disease.Main methods: In this study, we present a virtual screening procedure employing deep lerning regression method in 9101 drugs from Drug bank database against the target Main protease (Mpro) for the treatment of COVID-19. 500 screened compounds were subjected to docking.Key findings: Among those 500 drugs, 10 best drugs were selected, which had better binding energy as compared to the reference molecule. Based on the Binding energy score, we can suggest that the identified drug may be considered for therapeutic development against the virus.Significance: Drug repurposing has many advantages as it could shorten the time and reduce the cost of new drug discovery. This research will help to get new drugs against COVID-19 and help humans against this pandemic disease. Keyword- Drug Repurposing, Deep learning, Molecular Docking, COVID-19, Drug bank database, MPro

Download Full-text

Comparative Docking Analysis of Rational Drugs Against COVID-19 Main Protease

10.26434/chemrxiv.12136002.v1 ◽

2020 ◽

Author(s):

LALIT SAMANT ◽

Vyomesh Javle

Keyword(s):

Molecular Docking ◽

Treatment Options ◽

Docking Study ◽

Binding Energies ◽

Molecular Docking Study ◽

Docking Analysis ◽

Discovery Studio ◽

Main Protease ◽

Medicinal Use ◽

Lamarckian Genetic Algorithm

COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available, and investigations regarding COVID-19 treatment are lacking. Crystallised COVID-19 main protease (Mpro), which is a potential drug target. The present study aimed to assess drugs found in literature as potential COVID-19 Mpro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. The docking was cross-validated using Swiss Dock. COVID-19 Mpro was docked with several compounds, and docking was analysed by Biovia Discovery Studio 2020. Quinine and hydroxychloroquine were used as standards for comparison. The binding energies obtained from the docking of 6LU7, 2GTB with screened drugs viz., Quinine, Artesunate, Clotrimazol, Artemether, Quercetin, Mefloquine, ciprofloxacin, clindamycin, cipargamin, SJ-733 were in between -7.0 to -9.6 kcal/mol. On consideration of similar binding energy obtained from Autodock vina and SWISSDock and interaction residue pattern specifically (GLU 166,CYS 145, CYS44 and MET 49 residue) for SJ-733 & JPC-3210 may represent potential treatment options, and appeared to have the best potential to act as COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use against CoV.

Download Full-text