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

0574493 - BC 2024 RIV NL eng J - Článek v odborném periodiku
Straková, Petra - Bednář, Petr - Kotouček, J. - Holoubek, Jiří - Fořtová, A. - Svoboda, Pavel - Štefánik, M. - Huvarová, I. - Šimečková, P. - Mašek, J. - Gvozdev, D.A. - Mikhnovets, I.E. - Chistov, A.A. - Nikitin, T.D. - Krasilnikov, M.S. - Ustinov, A. - Alferova, V.A. - Korshun, V.A. - Růžek, Daniel - Eyer, Luděk
Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation.
Virus Research. Roč. 334, SEPT (2023), č. článku 199158. ISSN 0168-1702. E-ISSN 1872-7492
Grant CEP: GA MŠMT(CZ) LX22NPO5103
Institucionální podpora: RVO:60077344
Klíčová slova: SARS-CoV-2 * Perylene-related compound * Antiviral activity * Membrane * Liposome * Photodynamic inactivation
Obor OECD: Virology
Impakt faktor: 5, rok: 2022
Způsob publikování: Open access
https://www.sciencedirect.com/science/article/pii/S016817022300120X?via%3Dihub

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 per-ylene 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 repli-cation 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 photosen-sitization 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 mem-brane rheology.
Trvalý link: https://hdl.handle.net/11104/0345239