The spectroabsorptiometric and voltammetric behavior of malvin in buffered solutions and its antioxidant properties

In the present work the structural transformations of malvin in aqueous acetate buffer solutions were investigated over a wide pH range under in vitro conditions using electronic absorption spectroscopy. In addition to the spectroabsorptiometric investigation, the voltammetric behavior and the mechanism of the redox process of this molecule were studied, in order to define its antioxidant properties. The electronic absorption spectra reveal that the structural changes of malvin, caused by changes in the pH of the medium, lead to changes in the voltammetric behaviour of this molecule. The dependence of the oxidation potential of malvin on pH, which can be explained by the presence of different electroactive molecular structures of malvin at different pH values, indicates different mechanisms of the electrode process. The voltammetric activity of malvin is compared semiquantitatively with the voltammetric activity of a standard synthetic antioxidant, BHA, and a natural antioxidant, quercetin

An Integrative in Silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease

Aims: An infectious disease (COVID-19) caused by the coronavirus SARS-CoV-2 emerged in Wuhan, China in December 2019. Currently, SARS-CoV-2 infected more than 9 million people and caused more than 450 000 deaths. Considering the urgent need for novel therapeutics, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we investigated an integrative in silico drug repurposing approach as a valuable tool for rapid selection of potential candidates against SARS-CoV-2 Main Protease (Mpro).Main methods: To screen FDA-approved drugs, we designed an integrative in silico drug repurposing approach implementing structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data-mining analysis of drug-gene-COVID-19 association.Key findings: Through the presented approach, 43 candidates with potential inhibitory effect on Mpro were selected and further evaluated according to the predictions of tissue disposition, drug-gene-COVID-19 associations and potential pleiotropic effects. We singled out 9 FDA approved drugs as the most promising for their profiling in COVID-19 drug discovery campaigns. Our results were in agreement with current experimental findings, which validate the applied integrative approach and may support clinical decisions for a novel epidemic wave of COVID-19.Significance: To the best of our knowledge, this is the first integrative in silico repurposing study for COVID-19 with a clear advantage in linking structure-based molecular modeling of Mpro inhibitors with predictions of tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.</div