A threefold approach including quantum chemical, molecular docking and molecular dynamic studies to explore the natural compounds from Centaurea jacea as the potential inhibitors for COVID-19.

In the current report, we studied the possible inhibitors of COVID-19 from bioactive constituents of Centaurea jacea using a threefold approach consisting of quantum chemical, molecular docking and molecular dynamic techniques. Centaurea jacea is a perennial herb often used in folk medicines of dermatological complaints and fever. Moreover, anticancer, antioxidant, antibacterial and antiviral properties of its bioactive compounds are also reported. The Mpro (Main proteases) was docked with different compounds of Centaurea jacea through molecular docking. All the studied compounds including apigenin, axillarin, Centaureidin, Cirsiliol, Eupatorin and Isokaempferide, show suitable binding affinities to the binding site of SARS-CoV-2 main protease with their binding energies -6.7 kcal/mol, -7.4 kcal/mol, -7.0 kcal/mol, -5.8 kcal/mol, -6.2 kcal/mol and -6.8 kcal/mol, respectively. Among all studied compounds, axillarin was found to have maximum inhibitor efficiency followed by Centaureidin, Isokaempferide, Apigenin, Eupatorin and Cirsiliol. Our results suggested that axillarin binds with the most crucial catalytic residues CYS145 and HIS41 of the Mpro, moreover axillarin shows 5 hydrogen bond interactions and 5 hydrophobic interactions with various residues of Mpro. Furthermore, the molecular dynamic calculations over 60 ns (6×106 femtosecond) time scale also shown significant insights into the binding effects of axillarin with Mpro of SARS-CoV-2 by imitating protein like aqueous environment. From molecular dynamic calculations, the RMSD and RMSF computations indicate the stability and dynamics of the best docked complex in aqueous environment. The ADME properties and toxicity prediction analysis of axillarin also recommended it as safe drug candidate. Further, in vivo and in vitro investigations are essential to ensure the anti SARS-CoV-2 activity of all bioactive compounds particularly axillarin to encourage preventive use of Centaurea jacea against COVID-19 infections.

Inhibitory effect of thymoquinone from Nigella sativa against SARS-CoV-2 main protease. An in-silico study.

Nigella sativa is known for the safety profile, containing a wealth of useful antiviral compounds. The main protease (Mpro, 3CLpro) of severe acute respiratory syndrome 2 (SARS-CoV-2) is being considered as one of the most attractive viral target, processing the polyproteins during viral pathogenesis and replication. In the current investigation we analyzed the potency of active component, thymoquinone (TQ) of Nigella sativa against SARS-CoV-2 Mpro. The structures of TQ and Mpro was retrieved from PubChem (CID10281) and Protein Data Bank (PDB ID 6MO3) respectively. The Mpro and TQ were docked and the complex was subjected to molecular dynamic (MD) simulations for a period 50ns. Protein folding effect was analyzed using radius of gyration (Rg) while stability and flexibility was measured, using root means square deviations (RMSD) and root means square fluctuation (RMSF) respectively. The simulation results shows that TQ is exhibiting good binding activity against SARS-CoV-2 Mpro, interacting many residues, present in the active site (His41, Cys145) and also the Glu166, facilitating the pocket shape. Further, experimental approaches are needed to validate the role of TQ against virus infection. The TQ is interfering with pocket maintaining residues as well as active site of virus Mpro which may be used as a potential inhibitor against SARS-CoV-2 for better management of COVID-19.

Molecular docking, dynamics, and quantum chemical study of vanillylacetone and beta-hydroxy ketone derivatives against Mproof SARS-CoV-2

This study is carried out to find novel active drug candidates which can effectively bind to key residues of main protease (Mpro) of SARS-CoV-2. We performed molecular docking of fifty-seven (57) ligands from two classes: vanillylacetone and its derivatives and beta-hydroxy ketone derivatives against Mpro of SARS-CoV-2. We also docked three antiviral drugs as reference/benchmark drugs including remdesivir (RDV), chloroquine (CQ), and hydroxychloroquine (HCQ) against Mpro for comparison of inhibition tendencies of selected ligands. Binding energies of our reference drugs are as: CQ = -5.1 kcal mol-1 (with predicted inhibition constant (Ki pred) = 177 mu mol), HCQ = -5.7 kcal mol-1 (Ki pred = 64.07 mu mol) and RDV -6.3 kcal mol-1 (Ki pred = 13.95 mu mol). We got remarkable results for our docked ligands as 79% of total ligands indicated binding energies better than CQ, 39 % better than both HCQ and CQ, and 19 % better than all reference drugs. More interestingly interaction analysis of eight best-docked ligands showed that they interacted with desired key residues of Mpro. We further selected the four best-docked ligands L1 = -6.6 kcal mol-1 (Ki pred=13.95 mu mol), L6 = -7.0 kcal mol-1 (Ki pred = 7.08 mu mol), L34 = -6.0 kcal mol-1 (Ki pred = 38.54 mu mol), and L50 = -6.6 kcal mol-1 (Ki pred=13.95 mu mol) for further analysis by quantum chemical study, molecular dynamic (MD) simulations and ADMET analysis. We have also carried out MD-simulations of six more docked ligand L2, L14, L20, L36, L46 and L48 some of which were showing weak binding affinities and some average binding affinities to check their simulation behavior. Their RMSD, RMSF and binding free energy results were also quite satisfying. We believe the current investigation will evoke the scientific community and highlights the potential of selected compounds for potential use as antiviral compounds against Mpro of SARS-CoV-2.

Virtual screening of potential inhibitor against breast cancer-causing estrogen receptor alpha (ER alpha): molecular docking and dynamic simulations

Breast cancer (Bc(a)) causes the highest rate of mortality in females owing to the out-of-control cell division in breast cells. In this work, we perform an in-silico screening based on molecular docking and molecular dynamic of curcumin derivatives against ER alpha. In this study, we carry out, molecular docking of fifty (50) curcumin derivatives having anticancer potential by using virtual screening tools. Ten (10) ligands were selected based on binding energy ranged from (-7.4 kcal/mol to -9 kcal/mol), lower values of inhibition constant (0.23 mu mol to 3.59 mu mol), and visualisation of intermolecular interactions. Additionally, we also assess ADMET properties of selected ligands for prediction of their toxicity and drug-likeness. The molecular dynamic simulations (MD) including RMSD, RMSF, Rg, SASA, number of H-bonds and MM-PBSA binding free energy results showed that ligand L2 and L8 bind to estrogen protein ER alpha more proficiently with good stability over 120 ns. These results suggest lead anticancer compounds L2 (Salicylidenecurcumin) and L8 (Curcumin difluorinated) are the most promising inhibitor against ER alpha of Bc(a) with increment G(bind) values of (-2.939 and -4.369) kcal/mol. we expect that our findings will evoke the scientific community to further do in-vitro and in-vivo investigations for screened curcumin derivatives against ER alpha of Bc(a.)

In & nbsp;silico exploration of binding potentials of anti SARS-CoV-1 phytochemicals against main protease of SARS-CoV-2

The phytochemicals can play complementary medicine compared to synthetic drugs considering their natural origin, safety, and low cost. Phytochemicals hold a key position for the expansion of drug development against corona viruses and need better consideration to the agents that have already been shown to display effective activity against various strains of corona viruses. In this study, we performed molecular docking studies on potential forty seven phytochemicals which are SARS-CoV-1 M-pro inhibitors to identify potential candidate against the main proteins of SARS-CoV-2. In Silico Molecular docking studies revealed that phytochemicals 16 (Broussoflavan A), 22 (Dieckol), 31 (Hygromycin B), 45 (Sinigrin) and 46 (Theaflavin-3,3'-digallate) exhibited excellent SARS-CoV-2 Mpro inhibitors. Furthermore, supported by Molecular dynamics (MD) simulation analysis such as Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of gyration (Rg) and H-bond interaction analysis. We expect that our findings will provide designing principles for new corona virus strains and establish important frameworks for the future development of antiviral drugs.& nbsp;(C) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.& nbsp;

Isolation of phytochemicals from Malva neglecta Wallr and their quantum chemical, molecular docking exploration as active drugs against COVID-19

The Covid-19 pandemics caused by SARS-CoV-19, and the inadequacy of targeted medications, compelled scientists to seek new antiviral drugs. We present our current understanding of plant extracts containing polyphenols that inhibit Covid-19. Natural phytochemicals (polyphenols) derived from plants have the potential to establish research using extracts and/or individual compounds in the treatment and prevention of coronavirus. The polyphenolic drugs (antivirus) capable of inhibiting the coronavirus protein, that are vital for infection and virus replication. The benefit of phytochemicals is that they promote patient well-being while causing minimal side effects. To understand the antiviral behavior of isolated phytochemicals 1–6, various molecular descriptors, molecular electrostatic potential (MEP), and frontier molecular orbitals (FMO) were investigated. A systematic analysis of isolated phytochemicals was accomplished then molecular descriptors, docking score, active sites, and FMOs energies were compared to the commonly used drugs recently to treat COVID19, namely favipiravir, remdesivir dexamethasone and hydroxychloroquine. Using a molecular docking technique, we demonstrate for the first time that these plant phytochemicals can be inhibited by the core protease (6LU7) protein of COVID19. © 2021

Phenolic and flavonoid contents in Malva sylvestris and exploration of active drugs as antioxidant and anti-COVID19 by quantum chemical and molecular docking studies

The exploration of natural sources of antioxidant phytochemicals for human use with little toxicity gained worldwide attention. The preliminary screening of Malva sylvestris extracts revealed that its phytochemicals such as polyphenols, flavonoids and tannins, have high therapeutic potential. The total phenolic/flavonoids compounds of Malva sylvestris were extracted and isolated using bioassay guidelines, as well as in-silico studies. The extracts radical scavenging activity was further investigated using 1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide (NO) radical bioas-says. The antioxidant potentials of various fractions were compared to standard antioxidants such as ascorbic acid and quercetin. The dichloromethane extracts of Malva sylvestris exhibited the antiradical activity against DPPH and NO with radical scavenging activities (RSA) of 88.52 and 91.05% with IC50 values 22.11 and 19.01 mu g/mL respectively. Bio guided isolation form the dichloromethane sub fractions that afforded twelve phytochemicals. Furthermore, the frontier molecular orbitals (FMO), several molecular descriptors, electron affinity, ionization potential and molecular electrostatic potential (MEP) have been discussed to probe the active sites of various phytochemicals. A systematic study of isolated drugs was conducted, as well as docking, frontier molecular orbitals energies, active sites and molecular descriptors were compared with drugs currently used against COVID19 namely, dexamethasone, hydroxychloroquine, favipiravir and remdesivir. For the first time, through molecular docking approach, the inhibitions of these plant phytochemicals with NADPH were recorded to show antioxidant behavior and to explore anti-SARS-CoV-2 using core protease (6LU7) protein. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of King Saud University.

Synthesis of Copper(II) Coordination Complex, Its Molecular Docking and Computational Exploration for Novel Functional Properties: A Dual Approach

The present investigation uses a dual approach to study the copper (II) complex [Cu(phen)3]. (ClO4)2.HL.CH3CN (1) and its cationic complex- [Cu(II)(phen)3]2+ (1 a), where, HL = 4-Bromo-2((Z) -(naphthalene-4-ylimino)methyl)phenol, phen=1,10-phenanthroline. The complex (1) crystallized in the triclinic system of the space group P-1 with two molecules in the unit cell and reveals a distorted octahedral geometry. Inspiring by recent developments to find a potential inhibitor for the COVID-19 virus, we have also performed molecular docking study of [Cu(phen)3]+2 to see if our novel complex shows an affinity for the main protease (Mpro) of COVID-19 spike protein. Interestingly, the results are found quite encouraging where the binding affinity and inhibition constant were found to be −8.400 kcal/mol and 0.661 μM, respectively, for the best-docked confirmation of [Cu(II)(Phen)3]+2 complex with Mpro protein. This binding affinity is reasonably well as compared to recently known antiviral drugs. For instance, the binding affinity of [Cu(II)(Phen)3]+2 complex is found to be better than recently docking results of chloroquine (−6.293 kcal/mol), hydroxychloroquine (−5.573 kcal/mol) and remdesivir (−6.352 kcal/mol) with Mpro protein. Thus, we believe the broad-spectrum functional properties of our complex will provoke not only the interest of material chemists in materials designing but also incite the drug designing community. © 2021 Wiley-VCH GmbH

A threefold approach including quantum chemical, molecular docking and molecular dynamic studies to explore the natural compounds from Centaurea jacea as the potential inhibitors for COVID-19

In the current report, we studied the possible inhibitors of COVID-19 from bioactive constituents of Centaurea jacea using a threefold approach consisting of quantum chemical, molecular docking and molecular dynamic techniques. Centaurea jacea is a perennial herb often used in folk medicines of dermatological complaints and fever. Moreover, anticancer, antioxidant, antibacterial and antiviral properties of its bioactive compounds are also reported. The Mpro (Main proteases) was docked with different compounds of Centaurea jacea through molecular docking. All the studied compounds including apigenin, axillarin, Centaureidin, Cirsiliol, Eupatorin and Isokaempferide, show suitable binding affinities to the binding site of SARS-CoV-2 main protease with their binding energies -6.7 kcal/mol, -7.4 kcal/mol, -7.0 kcal/mol, -5.8 kcal/mol, -6.2 kcal/mol and -6.8 kcal/mol, respectively. Among all studied compounds, axillarin was found to have maximum inhibitor efficiency followed by Centaureidin, Isokaempferide, Apigenin, Eupatorin and Cirsiliol. Our results suggested that axillarin binds with the most crucial catalytic residues CYS145 and HIS41 of the Mpro, moreover axillarin shows 5 hydrogen bond interactions and 5 hydrophobic interactions with various residues of Mpro. Furthermore, the molecular dynamic calculations over 60 ns (6x106 femtosecond) time scale also shown significant insights into the binding effects of axillarin with Mpro of SARS-CoV-2 by imitating protein like aqueous environment. From molecular dynamic calculations, the RMSD and RMSF computations indicate the stability and dynamics of the best docked complex in aqueous environment. The ADME properties and toxicity prediction analysis of axillarin also recommended it as safe drug candidate. Further, in vivo and in vitro investigations are essential to ensure the anti SARS-CoV-2 activity of all bioactive compounds particularly axillarin to encourage preventive use of Centaurea jacea against COVID-19 infections.