The Computational Investigation of Sixteen Antiviral Drugs Against Main Protease (Mpro) and Spike Protease (Spro) of Sars-Cov-2

Kumer, Ajoy; Chakma, Unesco; Islam, Md. Tawhidul; Howlader, Debashis; Hossain, Tomal

doi:10.4067/s0717-97072021000405339

Cited by 5 publications

(5 citation statements)

References 23 publications

(24 reference statements)

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“…4 illustrates the graphical representation of HOMO and LUMO, their associated energy values, and the energy gap (Eg), which describes the total reactivity of the molecule. The calculated energy gap of the studied ligand is 3.88 eV, which makes it more stable than the previously reported metal complexes [48][49][50]. The HOMO electron density of the stable ligand is mainly observed as anti-bonding orbitals on the Cu ion and the nitrogen and oxygen atoms of the Quinaldinate frag-ment; whereas the LUMO electron density has a bonding nature that is localized on the π-electron multiple bonds of the two rings of the Quinaldinate component.…”

Section: Homo and Lumo Analysismentioning

confidence: 73%

Studying the Biological Activity of Trans-[Cu (quin)2(EtOH)2] as Potent Antimicrobial Cu(II) Complex through Computational Investigations: DFT, ADMET and Molecular Docking

Hussein¹,

El-Khayatt²,

Duaij³

et al. 2023

Front. Biosci. (Landmark Ed)

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Background:Trans-[Cu (quin)2(EtOH)2], a new copper (II) complex, was characterized using a variety of computational techniques to explore its biological role in pharmacological applications. Methods: The computational methods included density functional theory (DFT), ADMET and molecular docking. Results: The optimized geometrical parameters revealed that the plane containing the Cu ion and the Quinaldinate ligands was confirmed to be nearly planar. DFT findings suggest that the complex has a stable structure with a moderate band gap of 3.88 eV. Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO) analysis revealed a planar surface intramolecular charge transfer from its donor sites, in the center, to its ends instead of the vertical plane. Two electron-rich regions were observed around the oxygen ions in the molecular electrostatic potential (MEP) map, which were expected to be the sites of molecular bonding and interactions with target proteins. Drug-likeness and pharmacokinetics parameters were determined to provide insight into the safety level of the studied compound. The ADMET (absorption, distribution, metabolism, excretion, and toxicity) results showed favorable pharmacological features, as evidenced by a high oral bioavailability and a low risk of toxicity. A molecular docking study was performed by fitting the copper complex into the active sites of target proteins for Bacillus cereus, Staphylococcus aureus, and Escherichia coli bacteria. The title complex had the strongest antifungal effect within the inhibitory zone of B. cereus with a strong binding affinity of -9.83 kcal/mol. Also, maximum activity was exhibited against S.aureus (-6.65 kcal/mol) compared to the other recently reported Cu complexes within the limits of the screened references. Docking studies implicated modest inhibitory activity against E. coli bacteria. Conclusions: The findings highlighted the compound's biological activities and identified it as a possible treatment drug for the bacteria B. cereus and S. aureus.

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Section: Homo and Lumo Analysismentioning

confidence: 73%

Studying the Biological Activity of Trans-[Cu (quin)2(EtOH)2] as Potent Antimicrobial Cu(II) Complex through Computational Investigations: DFT, ADMET and Molecular Docking

Hussein¹,

El-Khayatt²,

Duaij³

et al. 2023

Front. Biosci. (Landmark Ed)

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“…When you say “electronic absorption,” you mean a change from the ground state to the first excited state. This is usually thought of as one electron moving from the HOMO state to the LUMO state ( Perepichka and Bryce, 2005 ; Kumer et al., 2021a ). A molecule’s high level of chemical stability and low level of chemical reactivity are directly linked to how long its energy difference lasts ( Kumer et al., 2022a ).…”

Section: Results and Analysismentioning

confidence: 99%

Mechanistic inhibition of Monkeypox and Marburg virus infection by O-rhamnosides and Kaempferol-o-rhamnosides derivatives: a new-fangled computational approach

Mashud

Kumer

Mukerjee

et al. 2023

Front. Cell. Infect. Microbiol.

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The increasing incidence of Monkeypox virus (Mpox) and Marburg virus (MARV) infections worldwide presents a significant challenge to global health, as limited treatment options are currently available. This study investigates the potential of several O-rhamnosides and Kaempferol-O-rhamnosides as Mpox and MARV inhibitors using molecular modeling methods, including ADMET, molecular docking, and molecular dynamics/MD simulation. The effectiveness of these compounds against the viruses was assessed using the Prediction of Activity Spectra for Substances (PASS) prediction. The study’s primary focus is molecular docking prediction, which demonstrated that ligands (L07, L08, and L09) bind to Mpox (PDB ID: 4QWO) and MARV (PDB ID: 4OR8) with binding affinities ranging from -8.00 kcal/mol to -9.5 kcal/mol. HOMO-LUMO based quantum calculations were employed to determine the HOMO-LUMO gap of frontier molecular orbitals (FMOs) and to estimate chemical potential, electronegativity, hardness, and softness. Drug similarity and ADMET prediction assessments of pharmacokinetic properties revealed that the compounds were likely non-carcinogenic, non-hepatotoxic, and rapidly soluble. Molecular dynamic (MD) modeling was used to identify the most favorable docked complexes involving bioactive chemicals. MD simulations indicate that varying types of kaempferol-O-rhamnoside are necessary for successful docking validation and maintaining the stability of the docked complex. These findings could facilitate the discovery of novel therapeutic agents for treating illnesses caused by the Mpox and MARV viruses.

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“…All the chemical structures were drawn by ChemDraw software 2012. 25 After that, the structures were optimized with the help of the avogadro Application for correcting the geometric configuration. 16 Finally, all the chemical structures were saved in protein data bank (PDB) file format for molecular docking analysis.…”

Section: Deoxycorticosterone Acetate (Doca)-induced Hypertensionmentioning

confidence: 99%

“…24 It is considered that the docking score higher than -6.0kcal/mol is active in the physiological system and can bind with the target receptor. 25 In this research, four targeted proteins (ACE inhibitor PDB ID 2X97, ACE inhibitor PDB ID 2X8Y, renin inhibitor PDB ID 2IKU and beta 2 adrenoceptor PDB ID 5X7D) have been taken and analyzed for their binding affinity with the selected ligands. At the same time, three FDA approved antihypertensive drugs (lisinopril, aliskiren and carazolol) are also studied to compare with newly screened ligands from the F. religiosa fruit fraction.…”

Section: Lipinski's Rule Pharmacokinetics and Drug Likenessmentioning

confidence: 99%

In vivo and In silico Analysis of Antihypertensive Activities of Ficus religiosa Fruit Extract

Shawon,

Sutradhar,

Akash

et al. 2024

Dhaka Univ. J. Pharm. Sci

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Hypertension is one of the major cardiovascular diseases leading to serious health consequences including cardiovascular events such as stroke and even death. These may also include significant damages to the body’s most organs like heart, kidneys and brain. This deadly disease requires proper treatment drugs with lower cost and fewer adverse effects. In this study, Ficus religiosa fruit has been selected as a candidate plant and its fruit extract was used to perform different pharmacological tests in hypertensive rat model. It was observed that the extract decreased the heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) moderately in comparison to deoxycorticosterone acetate (DOCA) in ethanol‑induced hypertensive rats. These effects were similar to that of atenolol, a standard antihypertensive drug. While testing liver function, it was seen that SGOT and SGPT levels were reduced significantly. The creatinine value was decreased to 0.43±0.2 U/L from 2.9±1.3 U/L (induced by DOCA) and 2.6±1.6 U/L (induced by ethanol). While observing cardiovascular parameters, the fruit extract given at dose of 400 mg/kg, lowered total Cholesterol (TC) to 97 mg/dl from 176 mg/dl, low-density lipoprotein (LDL) to 40 mg/dl from 75 mg/dl and Triglycerides (TG) to 61 mg/dl from 118 mg/dl. The increased values were induced by DOCA. In the same test, the high-density lipoprotein (HDL) was increased to 80 mg/dl from 44 mg/dl. These changes were comparable to those of the standard drug Atenolol. F. religiosa fruit contains different chemical constituents such as isofucosterol, leucopelargonidin, quercetin and beta sitosterol as reported earlier. Molecular docking studies with some of these constituents showed good binding affinity with the targeted protein (receptor) as compared to the standard drugs. Additionally, all the compounds have satisfied Lipinski’s rules and other pharmacokinetic parameters. Moreover, they showed no adverse effects in aquatic and non-aquatic environments. We, thus, conclude that F. religiosa fruit extract could be taken for the discovery of a safe alternative for managing hypertension. Dhaka Univ. J. Pharm. Sci. 23(1): 23-36, 2024 (June)

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The Computational Investigation of Sixteen Antiviral Drugs Against Main Protease (Mpro) and Spike Protease (Spro) of Sars-Cov-2

Cited by 5 publications

References 23 publications

Studying the Biological Activity of Trans-[Cu (quin)2(EtOH)2] as Potent Antimicrobial Cu(II) Complex through Computational Investigations: DFT, ADMET and Molecular Docking

Studying the Biological Activity of Trans-[Cu (quin)2(EtOH)2] as Potent Antimicrobial Cu(II) Complex through Computational Investigations: DFT, ADMET and Molecular Docking

Mechanistic inhibition of Monkeypox and Marburg virus infection by O-rhamnosides and Kaempferol-o-rhamnosides derivatives: a new-fangled computational approach

In vivo and In silico Analysis of Antihypertensive Activities of Ficus religiosa Fruit Extract

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