Novel pseudonucleosides and sulfamoyl-oxazolidinone ß-D-glucosamine derivative as anti-COVID-19: design, synthesis, and in silico study.

New pseudonucleosides containing cyclic sulfamide moiety and sulfamoyl ß-D-glucosamine derivative are described. These pseudonucleosides are synthesized in good yields starting from chlorosulfonyl isocyanate and ß-D-glucosamine hydrochloride in five steps; (protection, acetylation, removal of the Boc group, sulfamoylation, and cyclization). Further, novel glycosylated sulfamoyloxazolidin-2-one is prepared in three steps; carbamoylation, sulfamoylation, and intramolecular cyclization. The structures of the synthesized compounds were confirmed by usual spectroscopic and spectrometric methods NMR, IR, MS, and EA. Interesting molecular docking of the prepared pseudonucleosides and (Beclabuvir, Remdesivir) drugs with SARS-CoV-2/Mpro (PDB:5R80) was conducted using the same parameters for a fair comparison. A low binding affinity of the synthesized compounds compared to the Beclabuvir and other analysis showed that pseudonucleosides have the ability to inhibit SARS-CoV-2. After the motivating results of molecular docking study, the complex between the SARS-CoV-2 Mpro and compound 7 was subjected to 100 ns molecular dynamics (MD) simulation using Desmond module of Schrodinger suite, during which the receptor-ligand complex showed substantial stability after 10 ns of MD simulation. Also, we studied the prediction of absorption, distribution, properties of metabolism, excretion, and toxicity (ADMET) of the synthesized compounds.Communicated by Ramaswamy H. Sarma.

In-Silico Identification of Potent Inhibitors of COVID-19 Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) from Natural Products: Quercetin, Hispidulin, and Cirsimaritin Exhibited Better Potential Inhibition than Hydroxy-Chloroquine Against COVID-19 Main Protease Active Site and ACE2 (preprint)

COVID-19 is rapidly spreading and there are currently no specific clinical treatments available. The absence of an immediate available vaccine against SARS-CoV-2 made it hard for health professionals to tackle the problem. Thus, the need of ready to use prescription drugs or herbal remedies is urgent. SARS-CoV-2 main protease (Mpro) and Angiotensin Converting Enzyme2 (ACE2) protein structure are made available to facilitate finding solutions to the present problem. In this brief research, we compare the efficacy of some natural compounds against COVID-19 Mpro and ACE2 to that of Hydroxy-Chloroquine in silico.Molecular docking investigations were carried out using AutoDock. Virtual screening was performed using AutoDock Vina and the best ligand / protein mode was identified based on the binding energy. Amino Acids residues of ligands interactions were identified using PyMOL. According to present research results, Quercetin, Hispidulin, Cirsimaritin, Sulfasalazine, Artemisin and Curcumin exhibited better potential inhibition than Hydroxy-Chloroquine against COVID-19 main protease active site and ACE2. Our provided docking data of these compounds may help pave a way for further advanced research to the synthesis of novel drug candidate for COVID-19.