scholarly journals DFT, Molecular Docking, and ADME/Tox Screening Investigations of Market‑Available Drugs against SARS‑CoV‑2

2021 ◽  
Author(s):  
Joabe Araújo ◽  
Lucas de Sousa ◽  
Alice Sousa ◽  
Ruan Bastos ◽  
Gardênia Santos ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Docking Study ◽  
In Vitro Tests ◽  
Pharmacological Properties ◽  
Docking Simulations ◽  
Main Protease ◽  
Molecular Affinity

A series of drugs was investigated to determine structural, electronic and pharmacological properties, as well as the molecular affinity for the main protease of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2). The drugs were submitted to density functional theory calculations to optimize structures and predict binding preferences. The optimized geometries were used in molecular docking simulations. In the docking study, the receiver was considered rigid and the drugs flexible. The Lamarckian genetic algorithm with global search and Pseudo-Solis and Wets with local search were adopted for docking. Absorption, distribution, metabolism, excretion and toxicological properties were obtained from the Pre-ADMET online server. In this series, the antiviral atazanavir showed the potential to inhibit the main protease of SARS‑CoV‑2, based on the free binding energy, inhibition constant, binding interactions and its favorable pharmacological properties. Therefore, we recommend carrying out further studies with in vitro tests and subsequent clinical tests to analyze its effectiveness in the treatment of SARS‑CoV‑2.

scholarly journals Identification of Potent Inhibitors of COVID-19 Main Protease Enzyme by Molecular Docking Study

2020 ◽  
Author(s):  
pooja singh ◽  
Angkita Sharma ◽  
Shoma Paul Nandi
Keyword(s):  
Molecular Docking ◽  
Antiviral Drug ◽  
Cyclopiazonic Acid ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Docking Score ◽  
Protease Enzyme ◽  
Main Protease

<p>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 M<sup>pro</sup>, 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 <i>Aspergillus flavus</i> and <i>Aspergillus oryzae</i> 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 <i>in- vitro</i> and <i>in-vivo</i>.<b> </b></p>

Potential Bioactive glycosylated flavonoids as SARS-CoV-2 Main protease Inhibitors: A molecular Docking Study

2020 ◽  
Author(s):  
sabri ahmed cherrak ◽  
merzouk hafida ◽  
mokhtari soulimane nassima
Keyword(s):  
Molecular Docking ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
In Vivo Experiments ◽  
Main Protease

A novel (COVID-19) responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, testing existing drugs as inhibitors of the main COVID-19 protease is a good approach.Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules.The flavonoids chemical structures were downloaded from PubChem and protease structure 6lu7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the covid-19 protease and could be further investigated by in vitro and in vivo experiments for further validation.

scholarly journals Molecular Docking Study on Several Benzoic Acid Derivatives against SARS-CoV-2

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5828
Author(s):  
Amalia Stefaniu ◽  
Lucia Pirvu ◽  
Bujor Albu ◽  
Lucia Pintilie
Keyword(s):  
Molecular Docking ◽  
Benzoic Acid ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Principal Component ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Alkyl Gallates ◽  
Main Protease

Several derivatives of benzoic acid and semisynthetic alkyl gallates were investigated by an in silico approach to evaluate their potential antiviral activity against SARS-CoV-2 main protease. Molecular docking studies were used to predict their binding affinity and interactions with amino acids residues from the active binding site of SARS-CoV-2 main protease, compared to boceprevir. Deep structural insights and quantum chemical reactivity analysis according to Koopmans’ theorem, as a result of density functional theory (DFT) computations, are reported. Additionally, drug-likeness assessment in terms of Lipinski’s and Weber’s rules for pharmaceutical candidates, is provided. The outcomes of docking and key molecular descriptors and properties were forward analyzed by the statistical approach of principal component analysis (PCA) to identify the degree of their correlation. The obtained results suggest two promising candidates for future drug development to fight against the coronavirus infection.

scholarly journals Synthesis, characterization, in-vitro antimicrobial properties, molecular docking and DFT studies of 3-{(E)-[(4,6-dimethylpyrimidin-2-yl)imino]methyl} naphthalen-2-ol and Heteroleptic Mn(II), Co(II), Ni(II) and Zn(II) complexes

2018 ◽  
Vol 16 (1) ◽  
pp. 184-200 ◽  
Author(s):  
Festus Chioma ◽  
Anthony C. Ekennia ◽  
Aderoju A. Osowole ◽  
Sunday N. Okafor ◽  
Collins U. Ibeji ◽  
...  
Keyword(s):  
Schiff Base ◽  
Molecular Docking ◽  
Metal Complexes ◽  
Drug Targets ◽  
Density Functional ◽  
Radical Scavenging ◽  
Antimicrobial Properties ◽  
Density Functional Theory Calculations ◽  
Elemental Analyses

AbstractHeteroleptic divalent metal complexes [M(L) (bipy)(Y)]•nH2O (where M = Mn, Co, Ni, and Zn; L = Schiff base; bipy = 2,2’-bipyridine; Y = OAc and n = 0, 1) have been synthesized from pyrimidine Schiff base ligand 3-{(E)-[(4,6-dimethylpyrimidin-2-yl)imino]methyl} naphthalen-2-ol, 2,2’-bipyridine and metal(II) acetate salts. The Schiff base and its complexes were characterized by analytical (CHN elemental analyses, solubility, melting point, conductivity) measurements, spectral (IR, UV-vis, 1H and 13C-NMR and MS) and magnetometry. The elemental analyses, Uv-vis spectra and room temperature magnetic moment data provide evidence of six coordinated octahedral geometry for the complexes. The metal complexes’ low molar conductivity values in dimethylsulphoxide suggested that they were non-ionic in nature. The compounds displayed moderate to good antimicrobial and antifungal activities against S. aureus, P. aeruginosa, E. coli, B. cereus, P. mirabilis, K. oxytoca, A. niger, A. flevus and R. Stolonifer. The compounds also exhibited good antioxidant potentials with ferrous ion chelation and, 1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assays. Molecular docking studies showed a good interaction with drug targets used. The structural and electronic properties of complexes were further confirmed by density functional theory calculations.

scholarly journals A Dispersion Corrected DFT Investigation of the Inclusion Complexation of Dexamethasone with β-Cyclodextrin and Molecular Docking Study of Its Potential Activity against COVID-19

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7622
Author(s):  
Youghourta Belhocine ◽  
Seyfeddine Rahali ◽  
Hamza Allal ◽  
Ibtissem Meriem Assaba ◽  
Monira Galal Ghoniem ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Sites ◽  
Density Functional ◽  
Inclusion Complexation ◽  
Docking Study ◽  
Van Der Waals Interactions ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Docking Calculations ◽  
Potential Activity

The encapsulation mode of dexamethasone (Dex) into the cavity of β-cyclodextrin (β-CD), as well as its potential as an inhibitor of the COVID-19 main protease, were investigated using density functional theory with the recent dispersion corrections D4 and molecular docking calculations. Independent gradient model and natural bond orbital approaches allowed for the characterization of the host–guest interactions in the studied systems. Structural and energetic computation results revealed that hydrogen bonds and van der Waals interactions played significant roles in the stabilization of the formed Dex@β-CD complex. The complexation energy significantly decreased from −179.50 kJ/mol in the gas phase to −74.14 kJ/mol in the aqueous phase. A molecular docking study was performed to investigate the inhibitory activity of dexamethasone against the COVID-19 target protein (PDB ID: 6LU7). The dexamethasone showed potential therapeutic activity as a SARS CoV-2 main protease inhibitor due to its strong binding to the active sites of the protein target, with predicted free energy of binding values of −29.97 and −32.19 kJ/mol as calculated from AutoDock4 and AutoDock Vina, respectively. This study was intended to explore the potential use of the Dex@β-CD complex in drug delivery to enhance dexamethasone dissolution, thus improving its bioavailability and reducing its side effects.

scholarly journals Synthesis, characterization, synergistic antimicrobial properties and molecular docking of sugar modified uridine derivatives

2021 ◽  
Vol 32 (1) ◽  
pp. 6-21
Author(s):  
Jannatul Maowa ◽  
Asraful Alam ◽  
Kazi M. Rana ◽  
Sujan Dey ◽  
Anowar Hosen ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Density Functional ◽  
Antimicrobial Agents ◽  
Antimicrobial Properties ◽  
Docking Study ◽  
Bacterial Strains ◽  
Molecular Docking Study ◽  
Antibacterial And Antifungal Activities

Abstract Nucleosides and their analogues are an important, well-established class of clinically useful medicinal agents that exhibit antiviral and anticancer activity. Thus, our research group has focused on the synthesis of new nucleoside derivatives that could be tested for their broad-spectrum biological activity. In this study, two new series of nucleoside derivatives were synthesized from uridine (1) through facile two-step reactions using the direct acylation method, affording 5’-O-acyl uridine derivatives in good yields. The isolated uridine analogs were further transformed into two series of 2’,3’-di-O-acyl derivatives bearing a wide variety of functionalities in a single molecular framework to evaluate their antimicrobial activity. The new synthesized compounds were characterized through physicochemical, elemental and spectroscopic analysis, and all were screened for their in vitro antimicrobial activity against selected human and plant pathogenic strains. The test compounds revealed moderate to good antibacterial and antifungal activities and were more effective against fungal phytopathogens than against bacterial strains, while many of them exhibited better antimicrobial activity than standard antibiotics. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests against all microorganisms were also conducted for five compounds based on their activity (6, 11, 13, 16, and 17). In addition, all the derivatives were optimized using density functional theory (DFT) B3LYP/6-31g+(d,p) calculations to elucidate their thermal and molecular orbital properties. A molecular docking study was performed using the human protein 5WS1 to predict their binding affinity and modes, and ADMET and SwissADME calculations confirmed the improved pharmacokinetic properties of the compounds. Besides, structure–activity relationship (SAR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD) studies were also performed. Thus, the improvement of the bioactivity of these compounds is expected to significantly contribute to the design of more antimicrobial agents for therapeutic use in the future.

scholarly journals Preparation, Antimicrobial Activity and Docking Study of Vanadium Mixed Ligand Complexes Containing 4-Amino-5-hydrazinyl-4H-1,2,4-triazole-3-thiol and Aminophenol Derivatives

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 1008
Author(s):  
Doaa Domyati ◽  
Sami A. Zabin ◽  
Ahmed A. Elhenawy ◽  
Mohamed Abdelbaset
Keyword(s):  
Molecular Docking ◽  
Density Functional ◽  
Docking Study ◽  
Quantitative Structure Activity Relationship ◽  
Mixed Ligand ◽  
Mixed Ligand Complexes ◽  
Moderate Activity ◽  
Bacterial Strains ◽  
Functional Theory

The synthesis of mixed-ligand complexes is considered an important strategy for developing new metal complexes of enhanced biological activity. This paper presents the synthesis, characterization, in vitro antimicrobial assessment, and theoretical molecular docking evaluation for synthesized oxidovanadium (V) complexes. The proposed structures of the synthesized compounds were proved using elemental and different spectroscopic analysis. The antimicrobial tests showed moderate activity of the compounds against the Gram-positive bacterial strains and the fungal yeast, whereas no activity was observed against the Gram-negative bacterial strains. The performance of density functional theory (DFT) was conducted to study the interaction mode of the targeted compounds with the biological system. Calculating the quantitative structure-activity relationship (QSPR) was performed depending on optimization geometries, frontier molecular orbitals (FMOs), and chemical reactivities for synthesized compounds. The molecular electrostatic potentials (MEPs) that were plotted link the interaction manner of synthesized compounds with the receptor. The molecular docking evaluation revealed that the examined compounds may possess potential antibacterial activity.

scholarly journals Synthesis, In Silico and In Vitro Assessment of New Quinazolinones as Anticancer Agents via Potential AKT Inhibition

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4780 ◽  
Author(s):  
Ahmed A. Noser ◽  
Mohamed El-Naggar ◽  
Thoria Donia ◽  
Aboubakr H. Abdelmonsef
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Homo Sapiens ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Docking Simulations ◽  
Ic50 Values ◽  
Quinazolinone Derivatives ◽  
Mcf 7

A series of novel quinazolinone derivatives (2–13) was synthesized and examined for their cytotoxicity to HepG2, MCF-7, and Caco-2 in an MTT assay. Among these derivatives, compounds 4 and 9 exhibited significant cytotoxic activity against Caco-2, HepG2, and MCF-7 cancer cells. Compound 4 had more significant inhibitory effects than compound 9 on Caco-2, HepG2, and MCF-7 cell lines, with IC50 values of 23.31 ± 0.09, 53.29 ± 0.25, and 72.22 ± 0.14µM, respectively. The AKT pathway is one of human cancer’s most often deregulated signals. AKT is also overexpressed in human cancers such as glioma, lung, breast, ovarian, gastric, and pancreas. A molecular docking study was performed to analyze the inhibitory action of newly synthetic quinazolinone derivatives against Homo sapiens AKT1 protein. Molecular docking simulations were found to be in accordance with in vitro studies, and hence supported the biological activity. The results suggested that compounds 4 and 9 could be used as drug candidates for cancer therapy via its potential inhibition of AKT1 as described by docking study.

Some FDA Approved drugs exhibit binding affinity as high as -16.0 kcal/mol against COVID-19 Main Protease (Mpro): A Molecular Docking Study

2020 ◽  
Author(s):  
Shanmuga Subramanian
Keyword(s):  
Clinical Trials ◽  
Molecular Docking ◽  
Antiviral Agent ◽  
Binding Energies ◽  
In Vitro Tests ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Approved Drugs ◽  
Fda Approved Drugs

Currently the new Coronavirus "COVID-19", also known as SARS-CoV-2, has infected nearly 3 million patients and nearly 200,000+ people have lost their lives due to this pandemic. There is an urgent need to find an antiviral agent that may slow down the spread of the virus. The aim of this study is to assess and evaluate some FDA Approved drugs as potential inhibitors for COVID-19 Main Protease (Mpro) (PDB code: 6LU7). This will be done by blind molecular docking using PyRx and Auto Vina software. The compounds Hydroxychloroquine and Remdesivir were used for comparative study. The binding energies obtained from the docking of 6LU7 with Midostaurin, Zafirlukast, Eluxadoline, Naldemedine, Netupitant, Pancuronium, Letermovir, Baloxavir marboxil, Tazemetostat, Telotristat ethyl, Zeaxanthin, Lutein, Deserpidine, Cefotetan, Procaine benzylpenicillin were -16, 15.6, -15.3, -15.2, -15.1, -14.8, -14.6, -14.5, -13.8, -13.2, -13.2, -12.4, -12.4 and -11.2 kcal/mol respectively . Therefore some of the drugs can be used in Clinical trials as they are purified compounds of known composition and among all of them are approved drugs,some of them are investigative drugs except Pancuronium. All these drugs should be evaluated for further use by conducting in vitro tests and if they are successful they should evaluated for further use in clinical trials against COVID-19 as they are readily available in the market.

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