Tuning riboflavin derivatives for photodynamic inactivation of pathogens
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-10394-7 |
| _version_ | 1828402531545382912 |
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| author | Leander B. Crocker Ju Hyun Lee Suraj Mital Gabrielle C. Mills Sina Schack Andrea Bistrović-Popov Christoph O. Franck Ioanna Mela Clemens F. Kaminski Graham Christie Ljiljana Fruk |
| author_facet | Leander B. Crocker Ju Hyun Lee Suraj Mital Gabrielle C. Mills Sina Schack Andrea Bistrović-Popov Christoph O. Franck Ioanna Mela Clemens F. Kaminski Graham Christie Ljiljana Fruk |
| author_sort | Leander B. Crocker |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T10:01:49Z |
| format | Article |
| id | doaj.art-2eedeadfd21048bc94d98e5cc6c30881 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-10T10:01:49Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2eedeadfd21048bc94d98e5cc6c308812022-12-22T01:53:20ZengNature PortfolioScientific Reports2045-23222022-04-0112111110.1038/s41598-022-10394-7Tuning riboflavin derivatives for photodynamic inactivation of pathogensLeander B. Crocker0Ju Hyun Lee1Suraj Mital2Gabrielle C. Mills3Sina Schack4Andrea Bistrović-Popov5Christoph O. Franck6Ioanna Mela7Clemens F. Kaminski8Graham Christie9Ljiljana Fruk10Department of Chemical Engineering and Biotechnology, University of CambridgeDepartment of Chemical Engineering and Biotechnology, University of CambridgeDepartment of Chemical Engineering and Biotechnology, University of CambridgeDepartment of Chemical Engineering and Biotechnology, University of CambridgeDepartment of Chemical Engineering and Biotechnology, University of CambridgeDepartment of Chemical Engineering and Biotechnology, University of CambridgeDepartment of Chemical Engineering and Biotechnology, University of CambridgeDepartment of Chemical Engineering and Biotechnology, University of CambridgeDepartment of Chemical Engineering and Biotechnology, University of CambridgeDepartment of Chemical Engineering and Biotechnology, University of CambridgeDepartment of Chemical Engineering and Biotechnology, University of CambridgeAbstract 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.https://doi.org/10.1038/s41598-022-10394-7 |
| spellingShingle | Leander B. Crocker Ju Hyun Lee Suraj Mital Gabrielle C. Mills Sina Schack Andrea Bistrović-Popov Christoph O. Franck Ioanna Mela Clemens F. Kaminski Graham Christie Ljiljana Fruk Tuning riboflavin derivatives for photodynamic inactivation of pathogens Scientific Reports |
| title | Tuning riboflavin derivatives for photodynamic inactivation of pathogens |
| title_full | Tuning riboflavin derivatives for photodynamic inactivation of pathogens |
| title_fullStr | Tuning riboflavin derivatives for photodynamic inactivation of pathogens |
| title_full_unstemmed | Tuning riboflavin derivatives for photodynamic inactivation of pathogens |
| title_short | Tuning riboflavin derivatives for photodynamic inactivation of pathogens |
| title_sort | tuning riboflavin derivatives for photodynamic inactivation of pathogens |
| url | https://doi.org/10.1038/s41598-022-10394-7 |
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