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Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation.
Straková, Petra; Bednár, Petr; Kotoucek, Jan; Holoubek, Jirí; Fortová, Andrea; Svoboda, Pavel; Stefánik, Michal; Huvarová, Ivana; Simecková, Pavlína; Masek, Josef; Gvozdev, Daniil A; Mikhnovets, Igor E; Chistov, Alexey A; Nikitin, Timofei D; Krasilnikov, Maxim S; Ustinov, Alexey V; Alferova, Vera A; Korshun, Vladimir A; Ruzek, Daniel; Eyer, Ludek.
Afiliación
  • Straková P; Laboratory of Emerging Viral Diseases, Veterinary Research Institute, CZ-621 00 Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, CZ-370 05 Ceské Budejovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ
  • Bednár P; Laboratory of Emerging Viral Diseases, Veterinary Research Institute, CZ-621 00 Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, CZ-370 05 Ceské Budejovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ
  • Kotoucek J; Department of Pharmacology and Toxicology, Veterinary Research Institute, CZ-621 00 Brno, Czech Republic.
  • Holoubek J; Laboratory of Emerging Viral Diseases, Veterinary Research Institute, CZ-621 00 Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, CZ-370 05 Ceské Budejovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ
  • Fortová A; Laboratory of Emerging Viral Diseases, Veterinary Research Institute, CZ-621 00 Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ-62500 Brno, Czech Republic.
  • Svoboda P; Laboratory of Emerging Viral Diseases, Veterinary Research Institute, CZ-621 00 Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, CZ-370 05 Ceské Budejovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ
  • Stefánik M; Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-61300 Brno, Czech Republic.
  • Huvarová I; Laboratory of Emerging Viral Diseases, Veterinary Research Institute, CZ-621 00 Brno, Czech Republic.
  • Simecková P; Department of Pharmacology and Toxicology, Veterinary Research Institute, CZ-621 00 Brno, Czech Republic.
  • Masek J; Department of Pharmacology and Toxicology, Veterinary Research Institute, CZ-621 00 Brno, Czech Republic.
  • Gvozdev DA; Department of Biology, Lomonosov Moscow State University, Moscow, 119991, Russia.
  • Mikhnovets IE; Department of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia.
  • Chistov AA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia.
  • Nikitin TD; Department of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia.
  • Krasilnikov MS; Department of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia.
  • Ustinov AV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia.
  • Alferova VA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia.
  • Korshun VA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia.
  • Ruzek D; Laboratory of Emerging Viral Diseases, Veterinary Research Institute, CZ-621 00 Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, CZ-370 05 Ceské Budejovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ
  • Eyer L; Laboratory of Emerging Viral Diseases, Veterinary Research Institute, CZ-621 00 Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, CZ-370 05 Ceské Budejovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ
Virus Res ; 334: 199158, 2023 09.
Article en En | MEDLINE | ID: mdl-37339718
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted great interest in novel broad-spectrum antivirals, including perylene-related compounds. In the present study, we performed a structure-activity relationship analysis of a series of perylene derivatives, which comprised a large planar perylene residue, and structurally divergent polar groups connected to the perylene core by a rigid ethynyl or thiophene linker. Most of the tested compounds did not exhibit significant cytotoxicity towards multiple cell types susceptible to SARS-CoV-2 infection, and did not change the expressions of cellular stress-related genes under normal light conditions. These compounds showed nanomolar or sub-micromolar dose-dependent anti-SARS-CoV-2 activity, and also suppressed the in vitro replication of feline coronavirus (FCoV), also termed feline infectious peritonitis virus (FIPV). Perylene compounds exhibited high affinity for liposomal and cellular membranes, and efficiently intercalated into the envelopes of SARS-CoV-2 virions, thereby blocking the viral-cell fusion machinery. Furthermore, the studied compounds were demonstrated to be potent photosensitizers, generating reactive oxygen species (ROS), and their anti-SARS-CoV-2 activities were considerably enhanced after irradiation with blue light. Our results indicated that photosensitization is the major mechanism underlying the anti-SARS-CoV-2 activity of perylene derivatives, with these compounds completely losing their antiviral potency under red light. Overall, perylene-based compounds are broad-spectrum antivirals against multiple enveloped viruses, with antiviral action based on light-induced photochemical damage (ROS-mediated, likely singlet oxygen-mediated), causing impairment of viral membrane rheology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Perileno / COVID-19 Límite: Animals Idioma: En Revista: Virus Res Asunto de la revista: VIROLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Perileno / COVID-19 Límite: Animals Idioma: En Revista: Virus Res Asunto de la revista: VIROLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos