2. Academic Validation
  3. Membrane-Active Singlet Oxygen Photogenerators as a Paradigm for Broad-Spectrum Antivirals: The Case of Halogenated (BOron)-DIPYrromethenes

Membrane-Active Singlet Oxygen Photogenerators as a Paradigm for Broad-Spectrum Antivirals: The Case of Halogenated (BOron)-DIPYrromethenes

  • ACS Appl Mater Interfaces. 2025 Jan 22;17(3):4502-4528. doi: 10.1021/acsami.4c17482.
Xenia A Maryewski 1,  Maxim S Krasilnikov 1 2,  Petra Straková 3 4,  Jiří Holoubek 3 5 6,  Tereza Frčková 3 6,  Irina S Panina 1,  Nikolay A Krylov 1,  Daniil A Gvozdev 7,  Vladislav S Denisov 1 2,  Alexey N Semenov 7 8,  Natalia Y Lotosh 7,  Alla A Selishcheva 7,  Alexey A Chistov 1,  Evgeny L Gulyak 1,  Grigory L Kozhemyakin 9,  Vladimir A Korshun 1,  Roman G Efremov 1,  Alexey V Ustinov 1,  Daniel Růžek 3 5 6,  Luděk Eyer 3 5 6,  Vera A Alferova 1
Affiliations

Affiliations

  • 1 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
  • 2 Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia.
  • 3 Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296/70, CZ-621 00 Brno, Czech Republic.
  • 4 Laboratory of Clinical Immunology and Immunology of Infectious Diseases, Veterinary Research Institute, Hudcova 296/70, CZ-621 00 Brno, Czech Republic.
  • 5 Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branišovská 1160/31, CZ-370 05 České Budějovice, Czech Republic.
  • 6 Department of Experimental Biology, Faculty of Science, Masaryk University, CZ-62500 Brno, Czech Republic.
  • 7 Department of Biology, Lomonosov Moscow State University, Leninskie Gory 1-12, 119991 Moscow, Russia.
  • 8 Dynamics of Fluids, Department of Experimental Physics, Saarland University, Campus E2 6, 66123 Saarbrücken, Germany.
  • 9 Research Institute for Systems Biology and Medicine, 18 Nauchny proezd, 117246 Moscow, Russia.
PMID: 39772406 DOI: 10.1021/acsami.4c17482
Abstract

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.

Keywords

BODIPY; enveloped viruses; membrane-targeting photosensitizer; singlet oxygen photogeneration; virus-inactivating activity.

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