A molecular docking study of SARS-CoV-2 main protease against phytochemicals of Boerhavia diffusa Linn. for novel COVID-19 drug discovery

Within the span of a few months, the severe acute respiratory syndrome coronavirus, COVID-19 (SARS-CoV-2), has proven to be a pandemic, affecting the world at an exponential rate. It is extremely pathogenic and causes communicable infection in humans. Viral infection causes difficulties in breathing, sore throat, cough, high fever, muscle pain, diarrhea, dyspnea, and may lead to death. Finding a proper drug and vaccines against this virus is the need of the hour. The RNA genome of COVID19 codes for the main protease Mpro, which is required for viral multiplication. To identify possible antiviral drug(s), we performed molecular docking studies. Our screen identified ten biomolecules naturally present in Aspergillus flavus and Aspergillus oryzae fungi. These molecules include Aspirochlorine, Aflatoxin B1, Alpha-Cyclopiazonic acid, Sporogen, Asperfuran, Aspergillomarasmine A, Maltoryzine, Kojic acid, Aflatrem and Ethyl 3-nitropropionic acid, arranged in the descending order of their docking score. Aspirochlorine exhibited the docking score of – 7.18 Kcal/mole, higher than presently used drug Chloroquine (-6.2930522 Kcal/mol) and out of ten ligands studied four has docking score higher than chloroquine. These natural bioactive compounds could be tested for their ability to inhibit viral growth in- vitro and in-vivo.

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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>

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Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study

10.20944/preprints202004.0102.v3 ◽

2020 ◽

Cited By ~ 2

Author(s):

Trina Ekawati Tallei ◽

Sefren Geiner Tumilaar ◽

Nurdjannah Jane Niode ◽

Fatimawali Fatimawali ◽

Billy Johnson Kepel ◽

...

Keyword(s):

Free Energy ◽

Molecular Docking ◽

Bioactive Compounds ◽

Binding Free Energy ◽

Epigallocatechin Gallate ◽

Docking Study ◽

Molecular Docking Study ◽

Ligand Complex ◽

Main Protease ◽

Glycoprotein Inhibitors

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (Mpro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

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ADME predictions and molecular docking study of some compounds and drugs as potential inhibitors of COVID-19 main protease: A virtual study as comparison of computational results

Medicine Science | International Medical Journal ◽

10.5455/medscience.2020.09.203 ◽

2021 ◽

Vol 10 (1) ◽

pp. 18

Author(s):

Harun Uslu ◽

Pelin Koparir ◽

Kamuran Sarac ◽

Arzu Karatepe

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Computational Results ◽

Molecular Docking Study ◽

Main Protease ◽

Potential Inhibitors

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Identification of Bioactive Phytoconstituents from the Plant Euphorbia hirta as Potential Inhibitor of SARS-CoV-2: an In-Silico Approach

Biointerface Research in Applied Chemistry ◽

10.33263/briac122.13851396 ◽

2021 ◽

Vol 12 (2) ◽

pp. 1385-1396

Keyword(s):

Molecular Docking ◽

In Silico ◽

Biological Activities ◽

Specific Treatment ◽

Docking Study ◽

Docking Studies ◽

Molecular Docking Study ◽

Standard Drug ◽

Euphorbia Hirta ◽

Main Protease

Currently, the entire globe is under the deadliest pandemic of Covid-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). At present, no specific treatment is available to combat COVID-19 infection. Euphorbia hirta (Euphorbiaceae) have been reported for a variety of biological activities, including antiviral. The present investigation aimed to identify potential phytoconstituents of the plant E. hirta from the category flavonoids and coumarins against the SARS-CoV-2 using in silico approach. The molecular docking studies were performed using two different targets of SARS-CoV-2, namely Main protease (Mpro; PDB ID: 6M2N) and RNA-dependent RNA polymerase (RdRp; PDB ID: 7BW4). Based on the molecular docking study in comparison with standard drug, four compounds, namely Euphrobianin, Quercetin, 3-o-alpha-rhamnoside, Isoquercitrin, and rutin, were screened against the target Mpro. Three phytoconstituents, euphorbianin, myricetin, and rutin, were screened against the target RdRp. In the in silico toxicity studies of screened phytoconstituents, except myrectin all were predicted safe. Results of euphorbianin and rutin were found more interesting as both compounds had high binding affinity against both targets. Finally, we want to conclude that euphrobianin, quercetin 3-o-alpha-rhamnoside, isoquercitrin, and rutin could be further explored rapidly as they may have the potential to fight against COVID-19.

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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.

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Molecular Docking Study of Some Nucleoside Analogs against Main Protease of SARS-CoV-2

Eurasian Journal of Medicine and Oncology ◽

10.14744/ejmo.2020.94995 ◽

2020 ◽

Author(s):

Dhiraj Brahman

Keyword(s):

Molecular Docking ◽

Nucleoside Analogs ◽

Docking Study ◽

Molecular Docking Study ◽

Main Protease

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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.

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