Screening of Potent Inhibitors Against 2019 Novel Coronavirus (Covid-19) from Alliumsativum and Allium cepa: An In Silico Approach

2020 ◽  
Vol 11 (1) ◽  
pp. 7981-7993
Keyword(s):  
Molecular Docking ◽  
Allium Cepa ◽  
In Silico ◽  
Treatment Options ◽  
Natural Compounds ◽  
Binding Energies ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Main Protease

The infection of the global COVID-19 pandemic and the absence of any possible treatment options warrants the use of all available resources to find effective drugs against this scourge. Various ongoing researches have been searching for the new drug candidate against COVID-19 infection. The research objective is based on the molecular docking study of inhibition of the main protease of COVID-19 by natural compounds found in Allium sativum and Allium cepa. Lipinski rule of five and Autodock 4.2 was used by using the Lamarckian Genetic Algorithm to perform Molecular docking to analyze the probability of docking. Further, ADME analysis was also performed by using SwissADME, which is freely available on the web. In the present study, we identified S-Allylcysteine sulfoxide (Alliin), S-Propyl cysteine, S-Allylcysteine, S-Ethylcysteine, S-Allylmercaptocysteine, S-Methylcysteine, S-propyl L-cysteine with binding energies (-5.24, -4.49, -4.99, -4.91, -4.79, -4.76, -5.0 kcal/mol) as potential inhibitor candidates for COVID-19. Out of 7 selected compounds, alliin showed the best binding efficacy with target protein 6LU7. In silico ADME analysis revealed that these compounds are expected to have a standard drug-like property as well. Our findings propose that natural compounds from garlic and onion can be used as potent inhibitors against the main protease of COVID-19, which could be helpful in combating the COVID-19 pandemic.

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

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.

scholarly journals Potential Inhibitor of COVID-19 Main Protease (Mpro) From Several Medicinal Plant Compounds by Molecular Docking Study

2020 ◽  
Author(s):  
Siti Khaerunnisa ◽  
Hendra Kurniawan ◽  
Rizki Awaluddin ◽  
Suhartati Suhartati ◽  
Soetjipto Soetjipto
Keyword(s):  
Molecular Docking ◽  
Treatment Options ◽  
Docking Study ◽  
Binding Energies ◽  
Molecular Docking Study ◽  
Epicatechin Gallate ◽  
Discovery Studio ◽  
Main Protease ◽  
Lamarckian Genetic Algorithm ◽  
Autodock 4.2

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. Liu et al. (2020) successfully crystallised the COVID-19 main protease (Mpro), which is a potential drug target. The present study aimed to assess bioactive compounds found in medicinal plants 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. COVID-19 Mpro was docked with several compounds, and docking was analysed by Autodock 4.2, Pymol version 1.7.4.5 Edu, and Biovia Discovery Studio 4.5. Nelfinavir and lopinavir were used as standards for comparison. The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, epicatechin-gallate, zingerol, gingerol, and allicin were -8.37, -10.72, -9.41, -8.58, -8.47, -8.17, -7.99, -7.89, -7.83, -7.31, -7.05, -7.24, -6.67, -5.40, -5.38, and -4.03 kcal/mol, respectively. Therefore, nelfinavir and lopinavir may represent potential treatment options, and kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate appeared to have the best potential to act as COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use.

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

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.

scholarly journals Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study

2021 ◽  
Vol 22 (6) ◽  
pp. 2977
Author(s):  
Ahmed Abdelaal Ahmed Mahmoud M. Alkhatip ◽  
Michail Georgakis ◽  
Lucio R. Montero Valenzuela ◽  
Mohamed Hamza ◽  
Ehab Farag ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Energies ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
In Silico Docking ◽  
Main Protease ◽  
Binding Pockets

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at −8.3 kcal/mol, followed by Zn and Ca at −8.0 kcal/mol, and Fe and Mg at −7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn–Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.

In Silico Molecular Docking and Molecular Dynamic Simulation of Potential Inhibitors of 3C-like Main Proteinase (3CLpro) from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Using Selected African Medicinal Plants

2020 ◽  
Author(s):  
Sahar Qazi ◽  
Mustafa Alhaji Isa ◽  
Adam Mustapha ◽  
Khalid Raza ◽  
Ibrahim Alkali Allamin ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Severe Acute Respiratory Syndrome ◽  
In Silico ◽  
Md Simulation ◽  
Binding Energies ◽  
Anacardium Occidentale ◽  
Upper Respiratory Tract ◽  
Ligand Complex ◽  
In Silico Docking ◽  
Main Protease

<p>The Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) is an infectious virus that causes mild to severe life-threatening upper respiratory tract infection. The virus emerged in Wuhan, China in 2019, and later spread across the globe. Its genome has been completely sequenced and based on the genomic information, the virus possessed 3C-Like Main Protease (3CLpro), an essential multifunctional enzyme that plays a vital role in the replication and transcription of the virus by cleaving polyprotein at eleven various sites to produce different non-structural proteins. This makes the protein an important target for drug design and discovery. Herein, we analyzed the interaction between the 3CLpro and potential inhibitory compounds identified from the extracts of <i>Zingiber offinale</i> and <i>Anacardium occidentale</i> using in silico docking and Molecular Dynamics (MD) Simulation. The crystal structure of SARS-CoV-2 main protease in complex with 02J (5-Methylisoxazole-3-carboxylic acid) and PEJ (composite ligand) (PDB Code: 6LU7,2.16Å) retrieved from Protein Data Bank (PDB) and subject to structure optimization and energy minimization. A total of twenty-nine compounds were obtained from the extracts of <i>Zingiber offinale </i>and the leaves of <i>Anacardium occidentale. </i>These compounds were screened for physicochemical (Lipinski rule of five, Veber rule, and Egan filter), <i>Pan</i>-Assay Interference Structure (PAINS), and pharmacokinetic properties to determine the Pharmaceutical Active Ingredients (PAIs). Of the 29 compounds, only nineteen (19) possessed drug-likeness properties with efficient oral bioavailability and less toxicity. These compounds subjected to molecular docking analysis to determine their binding energies with the 3CLpro. The result of the analysis indicated that the free binding energies of the compounds ranged between ˗5.08 and -10.24kcal/mol, better than the binding energies of 02j (-4.10kcal/mol) and PJE (-5.07kcal.mol). Six compounds (CID_99615 = -10.24kcal/mol, CID_3981360 = 9.75kcal/mol, CID_9910474 = -9.14kcal/mol, CID_11697907 = -9.10kcal/mol, CID_10503282 = -9.09kcal/mol and CID_620012 = -8.53kcal/mol) with good binding energies further selected and subjected to MD Simulation to determine the stability of the protein-ligand complex. The results of the analysis indicated that all the ligands form stable complexes with the protein, although, CID_9910474 and CID_10503282 had a better stability when compared to other selected phytochemicals (CID_99615, CID_3981360, CID_620012, and CID_11697907). </p>

In Silico Molecular Docking and Molecular Dynamic Simulation of Potential Inhibitors of 3C-like Main Proteinase (3CLpro) from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Using Selected African Medicinal Plants

2020 ◽  
Author(s):  
Sahar Qazi ◽  
Mustafa Alhaji Isa ◽  
Adam Mustapha ◽  
Khalid Raza ◽  
Ibrahim Alkali Allamin ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Severe Acute Respiratory Syndrome ◽  
In Silico ◽  
Md Simulation ◽  
Binding Energies ◽  
Anacardium Occidentale ◽  
Upper Respiratory Tract ◽  
Ligand Complex ◽  
In Silico Docking ◽  
Main Protease

<p>The Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) is an infectious virus that causes mild to severe life-threatening upper respiratory tract infection. The virus emerged in Wuhan, China in 2019, and later spread across the globe. Its genome has been completely sequenced and based on the genomic information, the virus possessed 3C-Like Main Protease (3CLpro), an essential multifunctional enzyme that plays a vital role in the replication and transcription of the virus by cleaving polyprotein at eleven various sites to produce different non-structural proteins. This makes the protein an important target for drug design and discovery. Herein, we analyzed the interaction between the 3CLpro and potential inhibitory compounds identified from the extracts of <i>Zingiber offinale</i> and <i>Anacardium occidentale</i> using in silico docking and Molecular Dynamics (MD) Simulation. The crystal structure of SARS-CoV-2 main protease in complex with 02J (5-Methylisoxazole-3-carboxylic acid) and PEJ (composite ligand) (PDB Code: 6LU7,2.16Å) retrieved from Protein Data Bank (PDB) and subject to structure optimization and energy minimization. A total of twenty-nine compounds were obtained from the extracts of <i>Zingiber offinale </i>and the leaves of <i>Anacardium occidentale. </i>These compounds were screened for physicochemical (Lipinski rule of five, Veber rule, and Egan filter), <i>Pan</i>-Assay Interference Structure (PAINS), and pharmacokinetic properties to determine the Pharmaceutical Active Ingredients (PAIs). Of the 29 compounds, only nineteen (19) possessed drug-likeness properties with efficient oral bioavailability and less toxicity. These compounds subjected to molecular docking analysis to determine their binding energies with the 3CLpro. The result of the analysis indicated that the free binding energies of the compounds ranged between ˗5.08 and -10.24kcal/mol, better than the binding energies of 02j (-4.10kcal/mol) and PJE (-5.07kcal.mol). Six compounds (CID_99615 = -10.24kcal/mol, CID_3981360 = 9.75kcal/mol, CID_9910474 = -9.14kcal/mol, CID_11697907 = -9.10kcal/mol, CID_10503282 = -9.09kcal/mol and CID_620012 = -8.53kcal/mol) with good binding energies further selected and subjected to MD Simulation to determine the stability of the protein-ligand complex. The results of the analysis indicated that all the ligands form stable complexes with the protein, although, CID_9910474 and CID_10503282 had a better stability when compared to other selected phytochemicals (CID_99615, CID_3981360, CID_620012, and CID_11697907). </p>

scholarly journals MOLECULAR DOCKING STUDIES ON SCREENING AND ASSESSMENT OF SELECTED BIOFLAVONOIDS AS POTENTIAL INHIBITORS OF COVID-19 MAIN PROTEASE

2020 ◽  
pp. 174-178
Author(s):  
SHAILENDRA SANJAY SURYAWANSHI ◽  
POOJA BHAVAKANA JAYANNACHE ◽  
RAJKUMAR SANJAY PATIL ◽  
PALLED MS ◽  
ALEGAON SG
Keyword(s):  
Molecular Docking ◽  
Treatment Options ◽  
Docking Studies ◽  
Binding Energies ◽  
Molecular Docking Studies ◽  
Discovery Studio ◽  
Main Protease ◽  
Potential Inhibitors ◽  
Binding Energy Calculations ◽  
Native Ligand

Objectives: The objective of the study was to screen and assess the selected bioactive bioflavonoids in medicinal plants as potential coronaviruses (CoV) main protease (Mpro) inhibitors using molecular docking studies. Methods: We have investigated several bioflavonoids which include apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin. Nelfinavir and lopinavir were used as standard antiviral drugs for comparison. Mpro was docked with selected compounds using PyRx 0.8 and docking was analyzed by PyRx 0.8 and Biovia Discovery Studio 2019. Results: The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin were found to be −7.4, −8.3, −8.0, −7.8, −7.3, −7, −7.4, −7.6, −7.8, −6.9, and −9 kcal/mol, respectively. Conclusion: From the binding energy calculations, we can conclude that nelfinavir and lopinavir may represent potential treatment options and apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin found to possess the best inhibitors of CoV disease-19 main protease.

scholarly journals Anticancer Screening of the Phytochemicals Present in the Medicinal Plant Vitex Negundo Against Mutant Anaplastic Lymphoma Kinase (ALK) Protein: An In-Silico Approach

2019 ◽  
Vol 12 (2) ◽  
pp. 993-1000 ◽  
Author(s):  
D. Anusha ◽  
S. Sharanya ◽  
Ramya Ramya ◽  
Darling Chellathai David
Keyword(s):  
Molecular Docking ◽  
Medicinal Plant ◽  
Anaplastic Lymphoma Kinase ◽  
Natural Compounds ◽  
Binding Energies ◽  
Vitex Negundo ◽  
Molecular Docking Study ◽  
Selective Toxicity ◽  
Molegro Virtual Docker ◽  
Anaplastic Lymphoma

The lymphomas are a heterogeneous group of cancer of the lymphocytes and the lymphatic system and accounts for up to 3% of all malignancies.1 Most of the drugs currently used for the treatment of lymphoma produce various side effects, hence in this study, we focus on natural compounds, obtained from the medicinal plant Vitex negundo, which exhibits selective toxicity against cancer cells. The objective of this research was to formulate the binding energies and interaction of selected phytochemicals present in the medicinal plant Vitex negundo2 against anaplastic lymphoma kinase protein, which is overexpressed in an anaplastic large cell lymphoma.3, 4,5 The structure of mutant human anaplastic lymphoma kinase protein was retrieved from the Protein Data Bank (PDB ID:4ANL ) and the 3D chemical structure of the phytochemicals present in the medicinal plant Vitex negundo was obtained from the PubChem database. Molecular docking study was performed for these natural compounds to evaluate and analyze their anti-lymphoma-cancer activity. A total of 16 compounds present in Vitex negundo, based on a comprehensive literature survey was selected for this molecular screening. Molecular docking analysis was carried out by Molegro Virtual Docker software, to screen the 16 chosen compounds and rank them according to their binding affinity towards the site of interaction of the oncoprotein, anaplastic lymphoma kinase. Out of the 16 screened phytocompounds, only 4 compounds showed promising interactions against the oncoprotein ALK (4ANL). 6’-p-hydroxybenzoyl mussaenosidic acid exhibited a very good binding with a molecular docking score of -127.723 kcal/mol, ranking first among the compounds screened. This was followed by Betulinic acid, Viridiflorol and protocatechuic acid with molecular docking scores of -95.596 kcal/mol, -76.1648 kcal/mol and -63.0854 kcal/mol and - respectively. The docking scores from the above study shows that the phytocompounds present in Vitex negundo extract exhibits an effective inhibitory effect against anaplastic lymphoma kinase protein that is over expressed in lymphoma.

scholarly journals NATURAL ISOTHIOCYANATE ANTI-MALARIA: MOLECULAR DOCKING, PHYSICOCHEMICAL, ADME, TOXICITY AND SYNTHETIC ACCESSIBILITY STUDY OF EUGENOL AND CINNAMALDEHYDE

2021 ◽  
pp. 82-88
Author(s):  
LUCY ARIANIE ◽  
WIDODO ◽  
ELVINA DHIAUL IFTITAH ◽  
WARSITO
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Docking Method ◽  
Synthetic Accessibility ◽  
Medium Risk ◽  
Moringa Oleifera Leaves ◽  
Molecular Docking Method

Objective: This study aims to evaluate novel compounds of isothiocyanate (ITC) based on eugenol and cinnamaldehyde derivatives as the drug candidate of Plasmodium falciparum anti-malaria using in silico method, physicochemical, pharmacokinetics, toxicity, and synthetic accessibility prediction. This present study also describes molecular docking and pharmacoinformatics of natural ITC in Moringa oleifera leaves. Methods: A series of novel ITC compounds (3, 5, and 6) were designed and analyzed with a series of natural ITC compounds (7, 8, 9, 10) for P. falciparum anti-malaria. This research is descriptive qualitative and uses the reverse molecular docking method, proving the biological activity of compounds theoretically using software and database information. Results: Molecular docking study showed that compound 6 exhibits binding affinity (-5.3 Kcal/mol) on Van der Waals interaction with the residual active site (His159, Cys25) of cysteine protease. All designed ITC compounds are obeyed the Lipinski and Veber Rule, have a well-brain penetrant character and have a medium risk for mutagenic, tumorigenic, and reproductive prediction. They are also in the simple rate of synthetic accessibility (SA) estimation. In regards to natural ITCs, they all have better assay characteristics except the SA. Conclusion: Molecular docking, physicochemical, pharmacokinetic, and toxicity studies show that methyl eugenol isothiocyanate and cinnamaldehyde isothiocyanate are promising anti-malaria compounds. Substituents of hydroxy, acetate and tetrahydropyran groups in the building block ring are suggested for better in silico profiles enhancement.

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