Antiviral activity of singlet oxygen-photogenerating perylene
compounds against SARS-CoV-2: Interaction with the viral
envelope and photodynamic virion inactivation

J 2023

Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation

STRAKOVÁ, Petra, Petr BEDNÁŘ, Jan KOTOUČEK, Jiří HOLOUBEK, Andrea FOŘTOVÁ et. al.

Basic information

Original name

Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation

Authors

STRAKOVÁ, Petra (203 Czech Republic, belonging to the institution), Petr BEDNÁŘ (203 Czech Republic, belonging to the institution), Jan KOTOUČEK, Jiří HOLOUBEK (203 Czech Republic, belonging to the institution), Andrea FOŘTOVÁ (203 Czech Republic, belonging to the institution), Pavel SVOBODA (203 Czech Republic, belonging to the institution), 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 (203 Czech Republic, belonging to the institution) and Luděk EYER (203 Czech Republic, belonging to the institution)

Edition

Virus Research, Elsevier, 2023, 0168-1702

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10606 Microbiology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.000 in 2022

RIV identification code

RIV/00216224:14310/23:00131182

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1016/j.virusres.2023.199158

UT WoS

001037067400001

Keywords in English

SARS-CoV-2; Perylene-related compound; Antiviral activity; Membrane; Liposome; Photodynamic inactivation

Abstract

V originále

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.

Citovat

STRAKOVÁ, Petra, 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 and 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. Elsevier, 2023, vol. 334, September, p. 1-21. ISSN 0168-1702. Available from: https://dx.doi.org/10.1016/j.virusres.2023.199158.

@article{2296857,
   author = {Straková, Petra and Bednář, Petr and Kotouček, Jan and Holoubek, Jiří and Fořtová, Andrea and Svoboda, Pavel and Štefánik, Michal and Huvarová, Ivana and Šimečková, Pavlína and Mašek, Josef and Gvozdev, Daniil A and Mikhnovets, Igor E and Chistov, Alexey A and Nikitin, Timofei D and Krasilnikov, Maxim S and Ustinov, Alexey V and Alferova, Vera A and Korshun, Vladimir A and Růžek, Daniel and Eyer, Luděk},
   article_number = {September},
   doi = {http://dx.doi.org/10.1016/j.virusres.2023.199158},
   keywords = {SARS-CoV-2; Perylene-related compound; Antiviral activity; Membrane; Liposome; Photodynamic inactivation},
   language = {eng},
   issn = {0168-1702},
   journal = {Virus Research},
   title = {Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation},
   url = {https://doi.org/10.1016/j.virusres.2023.199158},
   volume = {334},
   year = {2023}
}

TY  - JOUR
ID  - 2296857
AU  - Straková, Petra - Bednář, Petr - Kotouček, Jan - Holoubek, Jiří - Fořtová, Andrea - Svoboda, Pavel - Štefánik, Michal - Huvarová, Ivana - Šimečková, Pavlína - Mašek, 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 - Růžek, Daniel - Eyer, Luděk
PY  - 2023
TI  - Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation
JF  - Virus Research
VL  - 334
IS  - September
SP  - 1-21
EP  - 1-21
PB  - Elsevier
SN  - 01681702
KW  - SARS-CoV-2
KW  - Perylene-related compound
KW  - Antiviral activity
KW  - Membrane
KW  - Liposome
KW  - Photodynamic inactivation
UR  - https://doi.org/10.1016/j.virusres.2023.199158
N2  - 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.
ER  -

STRAKOVÁ, Petra, 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 and Luděk EYER. Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation. \textit{Virus Research}. Elsevier, 2023, vol.~334, September, p.~1-21. ISSN~0168-1702. Available from: https://dx.doi.org/10.1016/j.virusres.2023.199158.

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