Suchergebnisse

The COVID-19 pandemic outbreak prompts an urgent need for efficient therapeutics, and repurposing of known drugs has been extensively used in an attempt to get to anti-SARS-CoV-2 agents in the shortest possible time. The glycoside rutin shows manifold pharmacological activities and, despite its use being limited by its poor solubility in water, it is the active principle of many pharmaceutical preparations. We herein report our in silico and experimental investigations of rutin as a SARS-CoV-2 Mpro inhibitor and of its water solubility improvement obtained by mixing it with l-arginine. Tests of the rutin/l-arginine mixture in a cellular model of SARS-CoV-2 infection highlighted that the mixture still suffers from unfavorable pharmacokinetic properties, but nonetheless, the results of this study suggest that rutin might be a good starting point for hit optimization. ; This research was in part founded with POR FESR 2014/2020, and thus, Regione Umbria is gratefully acknowledged (S.M.). This work was supported by Fundación hna (to A.V.-C. and O.A.); Fondo Investiga Covid-19 del Instituto de Investigación Sanitaria de Aragón IIS-A (to O.A. and A.V.-C.); Miguel Servet Program from Instituto de Salud Carlos III (CPII13/00017 to O.A.); Fondo de Investigaciones Sanitarias from Instituto de Salud Carlos III and the European Union (ERDF/ESF, "Investing in your future") (PI18/00349 to O.A. and a FIS Research Contract to L.C.-L.); Spanish Ministry of Economy and Competitiveness (BFU2016-78232-P to A.V.-C.); Spanish Ministry of Science, Innovation and Universities (FPI Predoctoral Research Contract BES-2017-080739 to D.O.-A.); Diputación General de Aragón (Predoctoral Research Contract 2019 to A.J.-A., 'Protein Targets and Bioactive Compounds Group' E45_20R to A.V.-C., 'Digestive Pathology Group' B25_20R to O.A.); and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd).This work was supported by the subsidy from the Polish Ministry of Science and Higher Education for research on SARS-CoV-2, a grant from the National Science Center UMO-2017/27/B/NZ6/02488, and EU-Horizon2020 ITN OrganoVir grant 812673 to KP. ; Peer reviewed

The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (Mpro) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent Mpro inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold. In particular, we report here a new synthetic method to prepare previously inaccessible C-8 seleno-quercetin derivatives. By screening a small library of flavonols and flavone derivatives, we observed that some compounds inhibit the protease activity in vitro. For the first time, we demonstrate that quercetin (1) and 8-(p-tolylselenyl)quercetin (2d) block SARS-CoV-2 replication in infected cells at non-toxic concentrations, with an IC50 of 192 μM and 8 μM, respectively. Based on docking experiments driven by experimental evidence, we propose a non-covalent mechanism for Mpro inhibition in which a hydrogen bond between the selenium atom and Gln189 residue in the catalytic pocket could explain the higher Mpro activity of 2d and, as a result, its better antiviral profile ; This work was supported by the University of Perugia "Fondo per la Ricerca di Base 2019"(C.S.); Fundación hna (to A.V.C. and O.A.); Miguel Servet Program from Instituto de Salud Carlos III (CPII13/00017 to O.A.); Fondo de Investigaciones Sanitarias from the Instituto de Salud Carlos III, and the European Union (ERDF/ESF, "Investing in your future") (PI18/00349 to O.A. and an FIS Research Contract to L.C.L.); Spanish Ministry of Economy and Competitiveness (BFU2016-78232-P to A.V.C.); Spanish Ministry of Science, Innovation and Universities (FPI Predoctoral Research Contract BES-2017-080739 to D.O.A.); Diputación General de Aragón (Predoctoral Research Contract 2019 to A.J.A., "Protein Targets and Bioactive Compounds Group" E45_20R to A.V.C., "Digestive Pathology Group" B25_20R to O.A.); and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. FAPERGS, CNPq, and FINEP are acknowledged for financial support. CNPq is also acknowledged for fellowships to E.J.L. and D.A. This work was supported by the subsidy from the Polish Ministry of Science and Higher Education for research on the ; Peer reviewed

Marine organisms produce a vast diversity of metabolites with biological activities useful for humans, e.g., cytotoxic, antioxidant, anti-microbial, insecticidal, herbicidal, anticancer, pro-osteogenic and pro-regenerative, analgesic, anti-inflammatory, anti-coagulant, cholesterol-lowering, nutritional, photoprotective, horticultural or other beneficial properties. These metabolites could help satisfy the increasing demand for alternative sources of nutraceuticals, pharmaceuticals, cosmeceuticals, food, feed, and novel bio-based products. In addition, marine biomass itself can serve as the source material for the production of various bulk commodities (e.g., biofuels, bioplastics, biomaterials). The sustainable exploitation of marine bio-resources and the development of biomolecules and polymers are also known as the growing field of marine biotechnology. Up to now, over 35,000 natural products have been characterized from marine organisms, but many more are yet to be uncovered, as the vast diversity of biota in the marine systems remains largely unexplored. Since marine biotechnology is still in its infancy, there is a need to create effective, operational, inclusive, sustainable, transnational and transdisciplinary networks with a serious and ambitious commitment for knowledge transfer, training provision, dissemination of best practices and identification of the emerging technological trends through science communication activities. A collaborative (net)work is today compelling to provide innovative solutions and products that can be commercialized to contribute to the circular bioeconomy. This perspective article highlights the importance of establishing such collaborative frameworks using the example of Ocean4Biotech, an Action within the European Cooperation in Science and Technology (COST) that connects all and any stakeholders with an interest in marine biotechnology in Europe and beyond. ; Funding text #1 AR and TR: the publication is part of a project that has received funding from the European Union ...