scholarly journals Synthesis of Novel Acylhydrazone-Oxazole Hybrids and Docking Studies of SARS-CoV-2 Main Protease

2020 ◽  
Vol 3 (1) ◽  
pp. 1
Author(s):  
Verónica G. García-Ramírez ◽  
Abel Suarez-Castro ◽  
Ma. Guadalupe Villa-Lopez ◽  
Erik Díaz-Cervantes ◽  
Luis Chacón-García ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
In Silico ◽  
Functional Group ◽  
Docking Studies ◽  
Synthetic Strategy ◽  
Protease Enzyme ◽  
Main Protease ◽  
Target Molecules ◽  
Van Leusen Reaction

A novel synthetic strategy to obtain acylhydrazone-oxazole hybrids in three-step reactions in moderate to good yields is reported. The key step reaction consists in a Van Leusen reaction using a bifunctional component of both an aldehyde and a functional group. The target molecules were evaluated via in-silico by molecular docking with the main protease enzyme of SARS-Cov-2, where two acyl hydralazine-oxazoles yielded good predicted free energy values in comparison to the co-crystalized ligand.

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 PREDIKSI SENYAWA EUCALYPTUS SEBAGAI INHIBITOR POTENSIAL COVID-19 MAIN PROTEASE (Mpro) SECARA MOLECULAR DOCKING

2021 ◽  
Vol 6 (2) ◽  
pp. 77
Author(s):  
Muhammad Fauzi ◽  
Fauzi Rahman ◽  
Yulistia Budianti Soemari ◽  
Richa Purnamasari
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Active Site ◽  
Docking Studies ◽  
Therapeutic Drug ◽  
Free Energies ◽  
Virus Family ◽  
Main Protease ◽  
The World ◽  
Suitable Target

The development of cases infected with the COVID-19 virus in Indonesia continues to increase. COVID-19 is a member of the corona virus family that has spread throughout the world. The COVID-19 Main protease is considered a suitable target for drug design against SARS infection because it plays a role in the processing of polyproteins required for the reproduction of the coronavirus. Eucalyptus are claimed to be able to ward off the COVID-19 virus. Therefore it is necessary to evaluate the content of eucalyptus compounds against Main proteases by docking studies. Based on the results of research conducted using the active site on the Main protease, it is known that eucalyptus (-)-globulol, epiglobulol, and ledol compounds have free energies of -7.23 kcal/mol, -7.91 kcal/mol, and -7.39 kcal/mol, respectively. Remdesivir as a therapeutic drug for COVID-19 has a free energy of -7.67 kcal/mol. These three compounds bind to the amino acid Glu166 as remdisivir with the best binding affinity on the active site of the Main protease. So these three compounds have the potential to inhibit the COVID-19 virus.

scholarly journals Bis-indolylation of aldehydes and ketones using silica-supported FeCl3: molecular docking studies of bisindoles by targeting SARS-CoV-2 main protease binding sites

RSC Advances ◽  
2021 ◽  
Vol 11 (49) ◽  
pp. 30827-30839
Author(s):  
Barnali Deb ◽  
Sudhan Debnath ◽  
Ankita Chakraborty ◽  
Swapan Majumdar
Keyword(s):  
Molecular Docking ◽  
Binding Site ◽  
Binding Sites ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Protease Enzyme ◽  
Main Protease ◽  
Simple Protocol ◽  
Aldehydes And Ketones

Silica supported FeCl3 catalyzed simple protocol for the synthesis of bis-indolylmethanes was explored via grindstone chemistry. Synthesized compounds were screened virtually as inhibitor by targeting the binding site of SARS-CoV-2 main protease enzyme.

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>

Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies

2020 ◽  
Vol 20 (3) ◽  
pp. 223-235
Author(s):  
Pooja Shah ◽  
Vishal Chavda ◽  
Snehal Patel ◽  
Shraddha Bhadada ◽  
Ghulam Md. Ashraf
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Reductase Activity ◽  
Infarct Volume ◽  
Docking Studies ◽  
Serum Glucose ◽  
In Vivo Studies ◽  
In Silico Molecular Docking

Background: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. Objective: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. Material and Methods: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. Results: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. Conclusion: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

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