Deleobuvir Sodium

Drug re-purposing might be a fast and efficient way of drug development against the novel coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We applied a bioinformatics approach using molecular dynamics and docking to identify FDA-approved drugs that can be re-purposed to potentially inhibit the non-structural protein 9 (Nsp9) replicase and spike proteins in SARS-CoV-2. We performed virtual screening of FDA-approved compounds, including antiviral, anti-malarial, anti-parasitic, anti-fungal, anti-tuberculosis, and active phytochemicals against the Nsp9 replicase and spike proteins. Selected hit compounds were identified based on their highest binding energy and favorable absorption, distribution, metabolism and excretion (ADME) profile. Conivaptan, an arginine vasopressin antagonist drug exhibited the highest binding energy (-8.4 Kcal/mol) and maximum stability with the amino acid residues present at the active site of the Nsp9 replicase. Tegobuvir, a non-nucleoside inhibitor of the hepatitis C virus, also exhibited maximum stability along with the highest binding energy (-8.1 Kcal/mol) at the active site of the spike proteins. Molecular docking scores were further validated by molecular dynamics using Schrodinger, which supported the strong stability of ligands with the proteins at their active sites through water bridges, hydrophobic interactions, and H-bonding. Our findings suggest Conivaptan and Tegobuvir as potential therapeutic agents against SARS-CoV-2. Further in vitro and in vivo validation and evaluation are warranted to establish how these drug compounds target the Nsp9 replicase and spike proteins.

HCV-genotype-4 (HCV-GT4) is the cause of approx. 20% of the 170 million cases of chronic hepatitis C virus (HCV) in the world.Around 95% of patients with chronic HCV infection can be cure by utilizing direct-acting antiviral treatment.Two anti-HCV genotype 4 co-administered ravidasvir (RAV) and sofosbuvir (SOF) were simultaneously quantified in rat plasma by a validated and sensitive LC-MS/MS method using aciclovir as an internal standardChromatog. resolution for all analytes was performed with an Eclipse plus C18 column (50 mm x 2.1 mm, 1.8μm) with isocratic mobile phase consisted of 10 mM ammonium formate: acetonitrile (61:39, volume/volume, pH 4.0) at a flow rate of 0.25 mL/min.Sample pre-treatment involved protein precipitation in plasma and stable internal standard resulted in a sensitive and robust method.Pos. multiple reaction monitoring (MRM) mode was chosen to identify RAV, SOF, and IS.The developed assay was validated for accuracy, precision, linearity, selectivity, extraction recovery, matrix effect, carry-over, dilution integrity, and stability in accordance with US-FDA bioanal. method validation guidelines.The method was linear over the ranges of 0.5-600 and 1-3000 ng/mL of RAV and SOF, resp. (r2 ≥ 0.997).After injection of the HLOQ sample, carry-over in the blank sample was less than 20% of the LLOQ of RAV, SOF and less than 5% of the IS.The mean relative standard deviation (RSD) of the results of accuracy and precision were ≤9.74%, and the overall recoveries of RAV and SOF from rat plasma were in the range 92.53-107.25%.The current methodol. is the first LC-MS/MS for the quantification of RAV and SOF in rat plasma and to applied the pharmacokinetics of these agents in rats.