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

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.

Anti-lung cancer drug discovery approaches by polysaccharides: an in silico study, quantum calculation and molecular dynamics study.

Lung cancer (LC) is one of the major and risky health defects even the serious cause for death in concurrent era. But no potential drugs even chemotherapeutic agents have been discovered with approval of health safety although some non-toxic biological macromolecules, such as polysaccharides and polysaccharide-protein complexes, have obtained as anti-lung cancer properties. This study conveys the anti-lung cancer properties of 45 polysaccharide derivatives collected from PubChem database. Primarily, the PASS prediction was performed to depict their anti-cancer activity, and 37 compounds showed the desired results. Next, the chemical descriptors, such as HOMO, LUMO, softness, and hardness etc, were calculated through the density functional theory (DFT) for quantum properties. Secondly, the auto molecular docking was executed to delineate the protein-ligand interactions, binding ability and inhibition of active sites of proteins. Additionally, the compounds showed docking score more than -6.40 kcal/mol, and the highest binding affinity was at -10.00 kcal/mol even 15 compounds have higher binding score (-8.6 to -10.0) than approved drugs, Gemcitabine. Succeeding, the most common protein residue, VAL 647, was blocked by ligands for the main protein (1X2J). In addition, five protein's active sites were determined to make the relative study of protein-ligand interactions. As a result, the target docking against five proteins was performed, and it was found that the targeted docking score as the binding affinity is lower than auto docking. Finally, a comparative study between auto docking and targeted docking was performed for the most common five lung cancer proteins founded in three organisms.Communicated by Ramaswamy H. Sarma.

Investigation of the New Inhibitors by Sulfadiazine and Modified Derivatives of α-D-glucopyranoside for White Spot Syndrome Virus Disease of Shrimp by In Silico: Quantum Calculations, Molecular Docking, ADMET and Molecular Dynamics Study.

The α-D-glucopyranoside and its derivatives were as the cardinal investigation for developing an effective medication to treat the highest deadly white spot syndrome virus (WSSV) diseases in Shrimp. In our forthcoming work, both computational tools, such as molecular docking, quantum calculations, pharmaceutical kinetics, ADMET, and their molecular dynamics, as well as the experimental trial against WSSV, were executed to develop novel inhibitors. In the beginning, molecular docking was carried out to determine inhibitors of the four targeted proteins of WSSV (PDB ID: 2ED6, 2GJ2, 2GJI, and 2EDM), and to determine the binding energies and interactions of ligands and proteins after docking. The range of binding affinity was found to be between -5.40 and -7.00 kcal/mol for the protein 2DEM, from -5.10 to 6.90 kcal/mol for the protein 2GJ2, from -4.70 to -6.2 kcal/mol against 2GJI, and from -5.5 kcal/mol to -6.6 kcal/mol for the evolved protein 2ED6 whereas the L01 and L03 display the highest binding energy in the protein 2EDM. After that, the top-ranked compounds (L01, L02, L03, L04, and L05), based on their high binding energies, were tested for molecular dynamics (MD) simulations of 100 ns to verify the docking validation and stability of the docked complex by calculating the root mean square deviation (RMSD) and root mean square fluctuation (RMSF). The molecules with the highest binding energy were then picked and compared to the standard drugs that were been applied to fish experimentally to evaluate the treatment at various doses. Consequently, approximately 40-45% cure rate was obtained by applying the dose of oxytetracycline (OTC) 50% with vitamin C with the 10.0 g/kg feed for 10 days. These drugs (L09 to L12) have also been executed for molecular docking to compare with α-D-glucopyranoside and its derivatives (L01 to L08). Next, the evaluation of pharmacokinetic parameters, such as drug-likeness and Lipinski's principles; absorption; distribution; metabolism; excretion; and toxicity (ADMET) factors, were employed gradually to further evaluate their suitability as inhibitors. It was discovered that all ligands (L01 to L12) were devoid of hepatotoxicity, and the AMES toxicity excluded L05. Additionally, all of the compounds convey a significant aqueous solubility and cannot permeate the blood-brain barrier. Moreover, quantum calculations based on density functional theory (DFT) provide the most solid evidence and testimony regarding their chemical stability, chemical reactivity, biological relevance, reactive nature and specific part of reactivity. The computational and virtual screenings for in silico study reveals that these chosen compounds (L01 to L08) have conducted the inhibitory effect to convey as a possible medication against the WSSV than existing drugs (L09, L10, L11 and L12) in the market. Next the drugs (L09, L10, L11 and L12) have been used in trials.