Identification of some dietary flavonoids as potential inhibitors of TMPRSS2 through protein-ligand interaction studies and binding free energy calculations.

The continuing threat of COVID-19 and deaths need an urgent cost-effective pharmacological approach. Here, we examine the inhibitory activity of a group of dietary bioactive flavonoids against the human protease TMPRSS2, which plays a major role in SARS CoV-2 viral entry. After the molecular docking studies of a large number of flavonoids, four compounds with high binding scores were selected and studied in detail. The binding affinities of these four ligands, Amentoflavone, Narirutin, Eriocitrin, and Naringin, at the active site of the TMPRSS2 target, were investigated using MD simulations followed by MM-PBSA binding energy calculations. From the studies, a number of significant hydrophobic and hydrogen bonding interactions between the ligands and binding site amino residues of TMPRSS2 are identified which showcase their excellent inhibitory activity against TMPRSS2. Among these ligands, Amentoflavone and Narirutin showed MM-PBSA binding energy values of -155.57 and -139.71 kJ/mol, respectively. Our previous studies of the inhibitory activity of these compounds against the main protease of SARS-COV2 and the present study on TMPRSS2 strongly highlighted that Amentoflavone and Naringin can exhibit promising multi-target activity against SARS-CoV-2. Moreover, due to their wide availability, no side effects, and low cost, these compounds could be recommended as dietary supplements for COVID patients or for the development of SARS-CoV-2 treatments. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-01955-7.

A Review of Analytical Methods for the determination of Clopidogrel in Pharmaceuticals and Biological Matrices.

P2Y12 belongs to a group of G protein-coupled (GPCR) purinergic receptors and is a receptor for adenosine diphosphate (ADP). The P2Y12 receptor is involved in platelet aggregation and acts as a biological target for treating thromboembolisms and other clotting disorders. The use of Clopidogrel (CLO) has improved the morbidity and mortality endpoints including cardiovascular death, recurrent myocardial infarction (MI) and stroke at 30 days after percutaneous coronary intervention (PCI). CLO is one such drug that specifically and irreversibly inhibits the P2Y12 subtype of ADP receptor. This review delivers a detail description of various analytical methods published for the estimation of CLO and its combinations in pharmaceuticals and biological matrices. The review highlights the basic as well as advanced techniques performed for estimating CLO. The most commonly used assay techniques were UV and Visible spectrophotometry, high performance liquid chromatography (HPLC), high performance thin layer chromatography (HPTLC), micellar liquid chromatography (MLC), micellar electro kinetic chromatography (MEKC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Despite other analytical methods employed for the assay of CLO, the review reveals that the technique of HPLC with UV detection was widely used.