The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is significantly impacting human lives, overburdening the healthcare system and weakening global economies. Plant-derived natural compounds are being largely tested for their efficacy against COVID-19 targets to combat SARS-CoV-2 infection. The SARS-CoV-2 Main protease (Mpro) is considered an appealing target because of its role in replication in host cells. We curated a set of 7809 natural compounds by combining the collections of five databases viz Dr Duke's Phytochemical and Ethnobotanical database, IMPPAT, PhytoHub, AromaDb and Zinc. We applied a rigorous computational approach to identify lead molecules from our curated compound set using docking, dynamic simulations, the free energy of binding and DFT calculations. Theaflavin and ginkgetin have emerged as better molecules with a similar inhibition profile in both SARS-CoV-2 and Omicron variants.

• MeSH
• farmakoterapie COVID-19 * MeSH
• lidé MeSH
• pandemie MeSH
• proteasy MeSH
• SARS-CoV-2 * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cardiotonic steroids (CTS) are steroidal drugs, processed from the seeds and dried leaves of the genus Digitalis as well as from the skin and parotid gland of amphibians. The most commonly known CTS are ouabain, digoxin, digoxigenin and bufalin. CTS can be used for safer medication of congestive heart failure and other related conditions due to promising pharmacological and medicinal properties. Ouabain isolated from plants is widely utilized in in vitro studies to specifically block the sodium potassium (Na+/K+-ATPase) pump. For checking, whether ouabain derivatives are robust inhibitors of Na+/K+-ATPase pump, molecular docking simulation was performed between ouabain and its derivatives using YASARA software. The docking energy falls within the range of 8.470 kcal/mol to 7.234 kcal/mol, in which digoxigenin was found to be the potential ligand with the best docking energy of 8.470 kcal/mol. Furthermore, pharmacophore modeling was applied to decipher the electronic features of CTS. Molecular dynamics simulation was also employed to determine the conformational properties of Na+/K+-ATPase-ouabain and Na+/K+-ATPase-digoxigenin complexes with the plausible structural integrity through conformational ensembles for 100 ns which promoted digoxigenin as the most promising CTS for treating conditions of congestive heart failure patients.

• MeSH
• biologické modely MeSH
• difuze MeSH
• digoxin chemie   farmakologie   MeSH
• kvantitativní vztahy mezi strukturou a aktivitou MeSH
• ligandy MeSH
• ouabain chemie   farmakologie   MeSH
• reprodukovatelnost výsledků MeSH
• simulace molekulového dockingu * MeSH
• sodíko-draslíková ATPasa antagonisté a inhibitory   metabolismus   MeSH
• srdeční glykosidy farmakologie   MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH

Alzheimer's disease (AD) is one of the most significant neurodegenerative disorders and its symptoms mostly appear in aged people. Catechol-o-methyltransferase (COMT) is one of the known target enzymes responsible for AD. With the use of 23 known inhibitors of COMT, a query has been generated and validated by screening against the database of 1500 decoys to obtain the GH score and enrichment value. The crucial features of the known inhibitors were evaluated by the online ZINC Pharmer to identify new leads from a ZINC database. Five hundred hits were retrieved from ZINC Pharmer and by ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering by using FAF-Drug-3 and 36 molecules were considered for molecular docking. From the COMT inhibitors, opicapone, fenoldopam, and quercetin were selected, while ZINC63625100_413 ZINC39411941_412, ZINC63234426_254, ZINC63637968_451, and ZINC64019452_303 were chosen for the molecular dynamics simulation analysis having high binding affinity and structural recognition. This study identified the potential COMT inhibitors through pharmacophore-based inhibitor screening leading to a more complete understanding of molecular-level interactions.

• MeSH
• Alzheimerova nemoc farmakoterapie   enzymologie   patofyziologie   MeSH
• exprese genu MeSH
• farmaceutické databáze MeSH
• inhibitory katechol-O-methyltransferasy chemie   farmakologie   MeSH
• interakční proteinové domény a motivy MeSH
• katechol-O-methyltransferasa chemie   MeSH
• kinetika MeSH
• konformace proteinů, alfa-helix MeSH
• konformace proteinů, beta-řetězec MeSH
• lidé MeSH
• ligandy MeSH
• nootropní látky chemie   farmakologie   MeSH
• rychlé screeningové testy * MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• substrátová specifita MeSH
• terciární struktura proteinů MeSH
• termodynamika MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH