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Tuning riboflavin derivatives for photodynamic inactivation of pathogens.
Crocker, Leander B; Lee, Ju Hyun; Mital, Suraj; Mills, Gabrielle C; Schack, Sina; Bistrovic-Popov, Andrea; Franck, Christoph O; Mela, Ioanna; Kaminski, Clemens F; Christie, Graham; Fruk, Ljiljana.
  • Crocker LB; Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
  • Lee JH; Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
  • Mital S; Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
  • Mills GC; Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
  • Schack S; Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
  • Bistrovic-Popov A; Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
  • Franck CO; Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
  • Mela I; Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
  • Kaminski CF; Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
  • Christie G; Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
  • Fruk L; Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK. lf389@cam.ac.uk.
Sci Rep ; 12(1): 6580, 2022 04 21.
Article in English | MEDLINE | ID: covidwho-1805652
ABSTRACT
The development of effective pathogen reduction strategies is required due to the rise in antibiotic-resistant bacteria and zoonotic viral pandemics. Photodynamic inactivation (PDI) of bacteria and viruses is a potent reduction strategy that bypasses typical resistance mechanisms. Naturally occurring riboflavin has been widely used in PDI applications due to efficient light-induced reactive oxygen species (ROS) release. By rational design of its core structure to alter (photo)physical properties, we obtained derivatives capable of outperforming riboflavin's visible light-induced PDI against E. coli and a SARS-CoV-2 surrogate, revealing functional group dependency for each pathogen. Bacterial PDI was influenced mainly by guanidino substitution, whereas viral PDI increased through bromination of the flavin. These observations were related to enhanced uptake and ROS-specific nucleic acid cleavage mechanisms. Trends in the derivatives' toxicity towards human fibroblast cells were also investigated to assess viable therapeutic derivatives and help guide further design of PDI agents to combat pathogenic organisms.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Photochemotherapy / COVID-19 Type of study: Observational study / Prognostic study Limits: Humans Language: English Journal: Sci Rep Year: 2022 Document Type: Article Affiliation country: S41598-022-10394-7

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Photochemotherapy / COVID-19 Type of study: Observational study / Prognostic study Limits: Humans Language: English Journal: Sci Rep Year: 2022 Document Type: Article Affiliation country: S41598-022-10394-7