Prediction of anti-Alzheimer's activity of flavonoids targeting acetylcholinesterase in silico http://researchonline.ljmu.ac.uk/5218/ Article LJMU has developed LJMU Research Online for users to access the research output of the University more effectively. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in LJMU Research Online to facilitate their private study or for non-commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain.The version presented here may differ from the published version or from the version of the record. Please see the repository URL above for details on accessing the published version and note that access may require a subscription. Objective -The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AchE inhibition linking to the pote tial treat e t of Alzhei er's disease.Methodology -Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and QSAR were performed in silico. In vitro activity was evaluated by bioactivity staining ased o the Ell a 's ethod.Results -In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AchE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC50 was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative number 20 was the best scorer i.e., -31.6392 and IC50 was predicted as 6.025 nM. Conclusion -Results indicated that flavonoids could be efficient inhibitors of AchE and thus, could be useful in the management of Alzhei er's disease.

Background: The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, positive-sense, single-stranded RNA betacoronavirus of the family Coronaviridae. Papain-like protease (PLpro) of SARS CoV-2 is an important target of COVID-19 because it is a multifunctional cysteine protease essential for coronaviral replication. Large numbers of phytochemicals with varied chemical structures isolated from medicinal plants have been shown to possess antiviral activity. Some of these phytochemicals have been chosen on the basis of literature survey for this study. Reported inhibitors of the papain-like protease are taken as control and for QSAR study.Methods: Three dimensional structure of target was downloaded from Protein Data Bank and docked with phytochemicals & inhibitors by using software FlexX. Inhibitors of the papain-like protease were taken from binding database and QSAR analysis was performed by using EasyQSAR software.Results: Six phytochemicals: Baicalin, Rutin, Biopterin, Licoleafol, Luteolin and Quercetin shows stable bonding pattern with the target in compare to known inhibitors as it shows least score in docking, forms maximum number of hydrogen bonds with the active residues of the receptor. The predicted IC50 values of the phytochemicals are also better than the known inhibitors.Conclusion: Based on present observation of docking score of both phytochemicals and known inhibitors, IC50 value of known inhibitors and predicted IC50 of phytochemicals, we suggests above mentioned six phytochemicals may be the Papain-like protease (PLpro) targeted potent drug leads against Covid-19.

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The estrogen hormone receptor (ER) mediated gene expression mainly regulate the development and physiology of primary and secondary reproductive system alongside bone-forming, metabolism and behaviour. Over-expressed ER is associated with several pathological conditions and play a key role in breast cancer occurrence, progression and metastasis. Hibiscus sabdariffa L. or roselle is a rich source of naturally occurring polyphenolic compounds including anthocyanins and reportedly have strong estrogenic activity. To validate these findings, we have investigated the estrogen receptor binding affinity and safety of some previously recorded polyphenols using a suite of computational methods. Our investigation showed the estrogen-receptor binding potential of Pelargonidin, Delphinidin, Cyanidin, and Hibiscetin are more efficient than popular breast cancer drugs, Tamoxifen and Raloxifene, with favourable toxicological parameters and low half maximal inhibitory concentration. This is the first report to investigate the phytochemical basis of estrogenic activity of Hibiscus sabdariffa L.

<p>Background: COVID-19 caused by SARS-CoV-2 in December 2019 has become a pandemic</p><p>hazard to the community health. It is a respiratory difficulty causing fever, dry cough, fatigue,</p><p>shortness of breath, muscle aches and some instances lead to pneumonia. Coronaviruses have</p><p>large viral RNA Genomes and are single-stranded positive-sense RNA viruses. The nsp10/nsp16</p><p>protein is an important target because it is essential for the virus to replicate, the papain-like</p><p>protease (Nsp3), the main protease (Nsp5), the primary RNA-dependent RNA polymerase</p><p>(Nsp12) are also attractive drug targets for this disease. The uses of phytochemicals as</p><p>therapeutic agents have been increasing in recent years. Some antiviral phytochemicals were</p><p>taken based on literature survey for this study.</p><p>Methods: ADME parameters and drug like nature of phytochemicals were screened using</p><p>SwissADME web tool. Three dimensional structures of targets are downloaded from Protein</p><p>Data Bank and docked with phytochemicals & control by using software FlexX.</p><p>Results: Morin shows significant results in ADME screening and Drug likeness prediction</p><p>studies, it shows stable bonding pattern with all four targets in compare to other phytochemicals</p><p>and control, shows least score in docking and forms maximum number of hydrogen bonds with</p><p>the active residues of the receptors.</p><p>Conclusion: Based on present observation of docking results, ADME parameters and drug like</p><p>nature, we suggest that morin may be a potent new drug candidate against Covid-19.</p><p>Keywords: COVID-19, coronavirus, drug target, phytochemicals, Drug likeness, ADME,</p><p>docking, morin</p>