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Repositioning microbial biotechnology against COVID-19: the case of microbial production of flavonoids
Authors:Tobias Goris  Álvaro Pérez-Valero  Igor Martínez  Dong Yi  Luis Fernández-Calleja  David San León  Uwe T. Bornscheuer  Patricia Magadán-Corpas  Felipe Lombó  Juan Nogales
Affiliation:1. Department of Molecular Toxicology, Research Group Intestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, Nuthetal, Brandenburg, 14558 Germany;2. Research Unit “Biotechnology in Nutraceuticals and Bioactive Compounds-BIONUC”, Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo, Oviedo, Spain

Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain

Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain

Equal contribution.;3. Department of Systems Biology, Centro Nacional de Biotecnología, CSIC, Madrid, Spain;4. Department of Biotechnology & Enzyme Catalysis, Institute of Biochemistry, University Greifswald, Felix-Hausdorff-Str. 4, Greifswald, D-17487 Germany;5. Research Unit “Biotechnology in Nutraceuticals and Bioactive Compounds-BIONUC”, Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo, Oviedo, Spain

Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain

Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain;6. Research Unit “Biotechnology in Nutraceuticals and Bioactive Compounds-BIONUC”, Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo, Oviedo, Spain

Abstract:Coronavirus-related disease 2019 (COVID-19) became a pandemic in February 2020, and worldwide researchers try to tackle the disease with approved drugs of all kinds, or to develop novel compounds inhibiting viral spreading. Flavonoids, already investigated as antivirals in general, also might bear activities specific for the viral agent causing COVID-19, SARS-CoV-2. Microbial biotechnology and especially synthetic biology may help to produce flavonoids, which are exclusive plant secondary metabolites, at a larger scale or indeed to find novel pharmaceutically active flavonoids. Here, we review the state of the art in (i) antiviral activity of flavonoids specific for coronaviruses and (ii) results derived from computational studies, mostly docking studies mainly inhibiting specific coronaviral proteins such as the 3CL (main) protease, the spike protein or the RNA-dependent RNA polymerase. In the end, we strive towards a synthetic biology pipeline making the fast and tailored production of valuable antiviral flavonoids possible by applying the last concepts of division of labour through co-cultivation/microbial community approaches to the DBTL (Design, Build, Test, Learn) principle.
Keywords:
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