Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation
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 analysi...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Virus Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S016817022300120X |
| _version_ | 1797755855914926080 |
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| author | Petra Straková Petr Bednář Jan Kotouček Jiří Holoubek Andrea Fořtová Pavel Svoboda Michal Štefánik Ivana Huvarová Pavlína Šimečková Josef Mašek Daniil A. Gvozdev Igor E. Mikhnovets Alexey A. Chistov Timofei D. Nikitin Maxim S. Krasilnikov Alexey V. Ustinov Vera A. Alferova Vladimir A. Korshun Daniel Růžek Luděk Eyer |
| author_facet | Petra Straková Petr Bednář Jan Kotouček Jiří Holoubek Andrea Fořtová Pavel Svoboda Michal Štefánik Ivana Huvarová Pavlína Šimečková Josef Mašek Daniil A. Gvozdev Igor E. Mikhnovets Alexey A. Chistov Timofei D. Nikitin Maxim S. Krasilnikov Alexey V. Ustinov Vera A. Alferova Vladimir A. Korshun Daniel Růžek Luděk Eyer |
| author_sort | Petra Straková |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T17:53:09Z |
| format | Article |
| id | doaj.art-fd0ab337342043389ef0ffe6c5160678 |
| institution | Directory Open Access Journal |
| issn | 1872-7492 |
| language | English |
| last_indexed | 2024-03-12T17:53:09Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
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| series | Virus Research |
| spelling | doaj.art-fd0ab337342043389ef0ffe6c51606782023-08-03T04:22:31ZengElsevierVirus Research1872-74922023-09-01334199158Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivationPetra Straková0Petr Bednář1Jan Kotouček2Jiří Holoubek3Andrea Fořtová4Pavel Svoboda5Michal Štefánik6Ivana Huvarová7Pavlína Šimečková8Josef Mašek9Daniil A. Gvozdev10Igor E. Mikhnovets11Alexey A. Chistov12Timofei D. Nikitin13Maxim S. Krasilnikov14Alexey V. Ustinov15Vera A. Alferova16Vladimir A. Korshun17Daniel Růžek18Luděk Eyer19Laboratory 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 České Budějovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ-62500 Brno, Czech RepublicLaboratory 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 České Budějovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ-62500 Brno, Czech Republic; Faculty of Science, University of South Bohemia, Ceske Budejovice, CZ-37005, Czech RepublicDepartment of Pharmacology and Toxicology, Veterinary Research Institute, CZ-621 00 Brno, Czech RepublicLaboratory 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 České Budějovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ-62500 Brno, Czech RepublicLaboratory 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 RepublicLaboratory 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 České Budějovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ-62500 Brno, Czech Republic; Department of Pharmacology and Pharmacy, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, CZ-612 42 Brno, Czech RepublicDepartment of Chemistry and Biochemistry, Mendel University in Brno, CZ-61300 Brno, Czech RepublicLaboratory of Emerging Viral Diseases, Veterinary Research Institute, CZ-621 00 Brno, Czech RepublicDepartment of Pharmacology and Toxicology, Veterinary Research Institute, CZ-621 00 Brno, Czech RepublicDepartment of Pharmacology and Toxicology, Veterinary Research Institute, CZ-621 00 Brno, Czech RepublicDepartment of Biology, Lomonosov Moscow State University, Moscow, 119991, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, RussiaDepartment of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, RussiaLaboratory 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 České Budějovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ-62500 Brno, Czech RepublicLaboratory 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 České Budějovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, CZ-62500 Brno, Czech Republic; Corresponding author at: Veterinary Research Institute, Emerging Viral Diseases, Hudcova 296/70, CZ-621 00 Brno, Czech Republic.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.http://www.sciencedirect.com/science/article/pii/S016817022300120XSARS-CoV-2Perylene-related compoundAntiviral activityMembraneLiposomePhotodynamic inactivation |
| spellingShingle | Petra Straková Petr Bednář Jan Kotouček Jiří Holoubek Andrea Fořtová Pavel Svoboda Michal Štefánik Ivana Huvarová Pavlína Šimečková Josef Mašek Daniil A. Gvozdev Igor E. Mikhnovets Alexey A. Chistov Timofei D. Nikitin Maxim S. Krasilnikov Alexey V. Ustinov Vera A. Alferova Vladimir A. Korshun Daniel Růžek Luděk Eyer Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation Virus Research SARS-CoV-2 Perylene-related compound Antiviral activity Membrane Liposome Photodynamic inactivation |
| title | Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation |
| title_full | Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation |
| title_fullStr | Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation |
| title_full_unstemmed | Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation |
| title_short | Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation |
| title_sort | antiviral activity of singlet oxygen photogenerating perylene compounds against sars cov 2 interaction with the viral envelope and photodynamic virion inactivation |
| topic | SARS-CoV-2 Perylene-related compound Antiviral activity Membrane Liposome Photodynamic inactivation |
| url | http://www.sciencedirect.com/science/article/pii/S016817022300120X |
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