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

2020 ◽  
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 ◽  
Biological Activities ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Glycoprotein Inhibitors

Background: Since the outbreak of the coronavirus disease 2019 (COVID-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 cause of COVID-19. The search for plant-based antivirals against the SARS-CoV-2 is promising, as several plants have been shown to possess antiviral activities against betacoronaviruses (beta-CoVs) Objective: The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit Main Protease (Mpro) (PDB code: 6LU7) and Spike (S) Glycoprotein (PDB code: 6VXX) of SARS-CoV-2. Methods: Evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. For each compound that was docked, a rule of five was calculated to determine whether a compound with certain pharmacological or biological activities might have chemical and physical properties that would make it an active drug orally in humans. Determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. Results: The results showed that hesperidine, cannabinoids, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and cannabinoids 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. Conclusion: 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.

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

2020 ◽  
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 ◽  
Biological Activities ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Glycoprotein Inhibitors

Background: Since the outbreak of the coronavirus disease 2019 (COVID-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 cause of COVID-19. The search for plant-based antivirals against the SARS-CoV-2 is promising, as several plants have been shown to possess antiviral activities against betacoronaviruses (beta-CoVs) Objective: The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit Main Protease (Mpro) (PDB code: 6LU7) and Spike (S) Glycoprotein (PDB code: 6VXX) of SARS-CoV-2. Methods: Evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. For each compound that was docked, a rule of five was calculated to determine whether a compound with certain pharmacological or biological activities might have chemical and physical properties that would make it an active drug orally in humans. Determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. Results: The results showed that hesperidine, cannabinoids, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and cannabinoids had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro/3CLpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Conclusion: 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.

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

2020 ◽  
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.

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

Scientifica ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Trina Ekawati Tallei ◽  
Sefren Geiner Tumilaar ◽  
Nurdjannah Jane Niode ◽  
Fatimawali ◽  
Billy Johnson Kepel ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Bioactive Compounds ◽  
Binding Free Energy ◽  
Chemical Reactivity ◽  
Epigallocatechin Gallate ◽  
Nucleophilic Attack ◽  
Molecular Docking Study ◽  
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 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 (AV) 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 performed by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs’ free energy of binding/ Δ G ). As a comparison, nelfinavir (an antiretroviral drug), chloroquine, and hydroxychloroquine sulfate (antimalarial 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. This finding implied that 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. From quantum chemical DFT calculations, the ascending order of chemical reactivity of selected compounds was pectolinarin > hesperidin > rhoifolin > morin > epigallocatechin gallate. All isolated compounds’ C=O regions are preferable for an electrophilic attack, and O-H regions are suitable for a nucleophilic attack. Furthermore, Homo-Lumo and global descriptor values indicated a satisfactory remarkable profile for the selected compounds. 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 of drugs to treat infections caused by SARS-CoV-2. The present study identified plant-based compounds that can be further investigated in vitro and in vivo as lead compounds against SARS-CoV-2.

scholarly journals Analysis of flavonoid compounds of Orange (Citrus sp.) peel as anti-main protease of SARS-CoV-2: A molecular docking study

2022 ◽  
Vol 951 (1) ◽  
pp. 012078
Author(s):  
N B Maulydia ◽  
T E Tallei ◽  
B Ginting ◽  
R Idroes ◽  
D N illian ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Binding Free Energy ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Flavonoid Compounds ◽  
Global Pandemic ◽  
Main Protease ◽  
New Type ◽  
The City

Abstract SARS-CoV-2 is a new type of coronavirus that causes COVID-19. This virus was first detected in the city of Wuhan, China, at the end of 2019, and until now, it has become a global pandemic. The FDA recently approved Vekluty (remdesivir) for adults and certain pediatric patients who have COVID-19 and are sick enough to require hospitalization. One of the potential drug target candidates for SARS-CoV-2 is the main protease (Mpro). The purpose of this study was to analyze the flavonoid compounds found in orange (Citrus sp.) peel to determine its potential as anti-Mpro through a molecular docking study. The compounds were initially screened for drug-like properties and then docked using Autodock Vina in the PyRx emulator software. The docking results were visualized using the BIOVIA Discovery Visualizer 2020. The result showed that the binding free energy of hesperidin (-8.6 kcal/mol) was higher than nelfinavir (-8.5 kcal/mol). In addition, hesperitin (-7.3 kcal/mol), sakuranetin (-7.1 kcal/mol), isosacuranetin (-7.2 kcal/mol) and tetra-o-methylscutallerin (-6.8 kcal/mol) exhibited lower binding free energy value than control. Based on these results, hesperidin has the potential as an inhibitor of the main protease’s SARS-CoV-2.

Molecular docking study and development of an empirical binding free energy model for phosphodiesterase 4 inhibitors

2006 ◽  
Vol 14 (17) ◽  
pp. 6001-6011 ◽  
Author(s):  
Fernanda G. Oliveira ◽  
Carlos M.R. Sant’Anna ◽  
Ernesto R. Caffarena ◽  
Laurent E. Dardenne ◽  
Eliezer J. Barreiro
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Binding Free Energy ◽  
Docking Study ◽  
Energy Model ◽  
Molecular Docking Study ◽  
Phosphodiesterase 4 ◽  
Phosphodiesterase 4 Inhibitors ◽  
Free Energy Model

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

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.

scholarly journals MOLECULAR DOCKING STUDY BETWEEN 3 THAI MEDICINAL PLANTS COMPOUNDS AND COVID-19 THERAPEUTIC PROTEIN TARGETS: SARS-COV-2 MAIN PROTEASE, ACE-2, AND PAK-1

2021 ◽  
pp. 41-48
Author(s):  
SAFIRA CANDRA ASIH ◽  
RAFIDHA IRDIANI ◽  
MUHAMAD SAHLAN ◽  
MOHAMMAD NASIKIN
Keyword(s):  
Molecular Docking ◽  
Medicinal Plants ◽  
Profile Analysis ◽  
Binding Free Energy ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Protein Targets ◽  
Main Protease ◽  
Docking Approach ◽  
Thai Medicinal Plants

Objective: The present study aimed to evaluate those 3 compounds among 122 Thai natural products by using a molecular docking approach to inhibit Main Protease (Mpro) of SARS-CoV-2 (PDB code: 6Y2F), Angiotensin Converting Enzyme (ACE)-2 (PDB code: 1R4L), and PAK-1 kinase (PDB code: 5DEW). Methods: The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine and interaction profile analysis through 2-dimensional visualization using LigPlot+. The determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). Result: The results of this study indicate that overall, Panduratin A has the best affinity in inhibiting the main protease of SARS-CoV-2, ACE-2, and PAK-1 compared to other compounds. Conclusion: The three thai medicinal plants compound has the potential to be developed as specific therapeutic agents against COVID-19.

scholarly journals In Silico Study on N-Ferrocenylmethyl-N-Phenylpropionohydrazide and N-Ferrocenylmethyl-N-Pheylbenzohydrazide as Anticancer Drugs for Breast and Prostate Cancer

2018 ◽  
Vol 11 ◽  
pp. 17-25 ◽  
Author(s):  
Zegheb Nadjiba ◽  
Boubekri Chérifa ◽  
Touhami Lanez ◽  
Elhafnaoui Lanez
Keyword(s):  
Prostate Cancer ◽  
Free Energy ◽  
Molecular Docking ◽  
Hydrogen Bonds ◽  
Binding Free Energy ◽  
Docking Study ◽  
Dominant Mode ◽  
Molecular Docking Study ◽  
Docking Calculations ◽  
Breast And Prostate Cancer

Molecular docking calculations were used to evaluate the antitumor activities of N-ferrocenylmethyl-N-phenylpropanamide (FP) and N-ferrocenylmethyl-N-pheylbenzohydrazide (FH) against the enzymes of breast cancer 17-beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) and human steroidogenic cytochrome P450 17A1 prostate cancer mutant A105L (CYP17A1). The molecular docking study was performed using the open source AutoDock 4.2 software. The obtained results showed that both FP and FH bind with 17β-HSD1 and CYP17A1 via hydrogen bonds, binding free energy values for the adducts FH-17β-HSD1 and FH-CYP17A1 were respectively equal to-27.67 and-27.55 KJmol-1, while for the adducts FP-17β-HSD1 and FP-CYP17A1 they were respectively equal to-29.13 and 29.18 KJmol-1. The negative values and the magnitude of the obtained binding free energy indicated respectively the spontaneity and the electrostatic interaction of both ligands FP and FH with 17β-HSD1 and CYP17A1 receptors as the dominant mode. Finally the ligand FP binds more strongly to the receptor CYP17A1 and forms two respective hydrogen bonds with Arg96 and His373; this finding clearly indicate that FP is best qualified as potential drug candidature for breast and prostate cancer.

scholarly journals Hit Identification of a Novel Quinazoline Sulfonamide as a Promising EphB3 Inhibitor: Design, Virtual Combinatorial Library, Synthesis, Biological Evaluation, and Docking Simulation Studies

2021 ◽  
Vol 14 (12) ◽  
pp. 1247
Author(s):  
Kyeong Lee ◽  
Hossam Nada ◽  
Hyun Jung Byun ◽  
Chang Hoon Lee ◽  
Ahmed Elkamhawy
Keyword(s):  
Molecular Docking ◽  
Combinatorial Library ◽  
Binding Free Energy ◽  
Biological Activities ◽  
Hybrid Approach ◽  
Docking Simulation ◽  
Docking Study ◽  
Biological Evaluation ◽  
Molecular Docking Study ◽  
Hit Identification

EphB3 is a major key player in a variety of cellular activities, including cell migration, proliferation, and apoptosis. However, the exact role of EphB3 in cancer remains ambiguous. Accordingly, new EphB3 inhibitors can increase the understanding of the exact roles of the receptor and may act as promising therapeutic candidates. Herein, a hybrid approach of structure-based design and virtual combinatorial library generated 34 quinazoline sulfonamides as potential selective EphB3 inhibitors. A molecular docking study over EphB3 predicted the binding affinities of the generated library, and the top seven hit compounds (3a and 4a–f), with GlideScore ≥ −6.20 Kcal/mol, were chosen for further MM-GBSA calculations. Out of the seven top hits, compound 4c showed the highest MM-GBSA binding free energy (−74.13 Kcal/mol). To validate these predicted results, compounds 3a and 4a–f were synthesized and characterized using NMR, HRMS, and HPLC. The biological evaluation revealed compound 4c as a potent EphB3 inhibitory lead (IC50 = 1.04 µM). The screening of 4c over a mini-panel of kinases consisting of EGFR, Aurora A, Aurora B, CDK2/cyclin A, EphB1, EphB2, EphB4, ERBB2/HER2, and KDR/VEGFR2, showed a promising selective profile against EphB3 isoform. A dose-dependent assay of compound 4c and a molecular docking study over the different forms of EphB provided insights into the elicited biological activities and highlighted reasonable explanations of the selectivity.

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