Membrane-Active Singlet Oxygen Photogenerators as a Paradigm for Broad-Spectrum Antivirals: The Case of Halogenated (BOron)-DIPYrromethenes
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
39772406
DOI
10.1021/acsami.4c17482
Knihovny.cz E-zdroje
- Klíčová slova
- BODIPY, enveloped viruses, membrane-targeting photosensitizer, singlet oxygen photogeneration, virus-inactivating activity,
- MeSH
- antivirové látky * farmakologie chemie MeSH
- fotosenzibilizující látky * chemie farmakologie MeSH
- halogenace MeSH
- lidé MeSH
- lipidové dvojvrstvy chemie MeSH
- myši MeSH
- porfobilinogen * analogy a deriváty chemie farmakologie MeSH
- SARS-CoV-2 účinky léků MeSH
- singletový kyslík * chemie metabolismus MeSH
- sloučeniny boru * chemie farmakologie MeSH
- viry klíšťové encefalitidy účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene MeSH Prohlížeč
- antivirové látky * MeSH
- dipyrromethene MeSH Prohlížeč
- fotosenzibilizující látky * MeSH
- lipidové dvojvrstvy MeSH
- porfobilinogen * MeSH
- singletový kyslík * MeSH
- sloučeniny boru * MeSH
Enveloped viruses, such as flaviviruses and coronaviruses, are pathogens of significant medical concern that cause severe infections in humans. Some photosensitizers are known to possess virucidal activity against enveloped viruses, targeting their lipid bilayer. Here we report a series of halogenated difluoroboron-dipyrromethene (BODIPYs) photosensitizers with strong virus-inactivating activity. Our structure-activity relationship analysis revealed that BODIPY scaffolds with a heavy halogen atom demonstrate significant efficacy against both tick-borne encephalitis virus (TBEV; Flaviviridae family) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; Coronaviridae family) along with high singlet oxygen quantum yields. Moreover, select compounds also inactivated other enveloped viruses, such as herpes simplex virus type 1 and monkeypox virus. The nature and length of the alkyl side chain notably influenced the virus-inactivating activity of BODIPY molecules. Furthermore, molecular dynamics studies highlighted the critical importance of the positioning of the chromophore moiety within the lipid bilayer. As membrane-targeting photosensitizers, BODIPYs interact directly with virus particles, causing damage to the viral envelope membranes. Thus, TBEV pretreated with BODIPY was completely noninfective for lab mice. Consequently, BODIPY-based photosensitizers hold potential either as broad-spectrum virus-inactivating antivirals against a variety of phylogenetically unrelated enveloped viruses or as potent inactivators of viruses for the development of vaccines for preventing life-threatening emerging viral diseases.
Department of Biology Lomonosov Moscow State University Leninskie Gory 1 12 119991 Moscow Russia
Department of Chemistry Lomonosov Moscow State University Leninskie Gory 1 3 119991 Moscow Russia
Research Institute for Systems Biology and Medicine 18 Nauchny proezd 117246 Moscow Russia
Shemyakin Ovchinnikov Institute of Bioorganic Chemistry Miklukho Maklaya 16 10 117997 Moscow Russia
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