Author(s): Mendonça, Diogo A. ; Cadima-Couto, Iris ; Buga, Carolina C. ; Arnaut, Zoe A. ; Schaberle, Fabio A. ; Arnaut, Luis G. ; Castanho, Miguel A.R.B. ; Cruz-Oliveira, Christine
Date: 2024
Persistent ID: http://hdl.handle.net/10362/182756
Origin: Repositório Institucional da UNL
Subject(s): Antiviral agents; Membrane targeting; Porphyrin derivatives; SARS-CoV-2; Temoporfin; Verteporfin; Pharmacology; SDG 3 - Good Health and Well-being
Funding Information: This project has received funding from the European Union\u2019s Horizon 2020 research and innovation programme under grant agreement No 828774 and Funda\u00E7\u00E3o para a Ci\u00E9ncia e a Tecnologia, I.P., through project RESEARCH4COVID n\u00B0 470, MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020), LS4FUTURE Associated Laboratory (LA/P/0087/2020) and iNOVA4Health R&D Unit (UIDB/04462/2020, UIDP/04462/2020). Additional funding from Funda\u00E7\u00E3o para a Ci\u00E9ncia e a Tecnologia (FCT-MCTES) is also acknowledged for D.A.M. (PD/BD/136752/2018); \u00CD.C.-C. (PTDC/BIAVIR/29495/2017); C.C.B. (2022.13959.BD); Z.A.A (2021.09454.BD); FAS (PTDC/QUI -OUT/0303/2021). Funding Information: This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 828774 and Funda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia, I.P., through project RESEARCH4COVID n\u00B0 470, MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020), LS4FUTURE Associated Laboratory (LA/P/0087/2020) and iNOVA4Health R&D Unit (UIDB/04462/2020, UIDP/04462/2020). Additional funding from Funda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia, I.P. is also acknowledged for D.A.M. (PD/BD/136752/2018); \u00CD.C.-C. (PTDC/BIAVIR/29495/2017); C.C.B. (2022.13959.BD); Z.A.A (2021.09454.BD); FAS (PTDC/QUI -OUT/0303/2021). Publisher Copyright: © 2024 The Authors
Antiviral medicines to treat COVID-19 are still scarce. Porphyrins and porphyrin derivatives (PDs) usually present broad-spectrum antiviral activity with low risk of resistance development. In fact, some PDs are clinically approved to be used in anti-cancer photodynamic therapy and repurposing clinically approved PDs might be an alternative to treat COVID-19. Here, we characterize the ability of temoporfin, verteporfin, talaporfin and redaporfin to inactivate SARS-CoV-2 infectious particles. PDs light-dependent and –independent effect on SARS-CoV-2 infectivity were evaluated. PDs photoactivation successfully inactivated SARS-CoV-2 with very low concentrations and light dose. However, only temoporfin and verteporfin inactivated SARS-CoV-2 in the dark, being verteporfin the most effective. PDs treatment reduced viral load in infected Caco-2 cells, while not inducing cytotoxicity. Furthermore, light-independent treatment with temoporfin and verteporfin act on early stages of viral infection. Using lipid vehicles as membrane models, we characterized PDs interaction to the viral envelope. Verteporfin presented the lowest IC50 for viral inactivation and the highest partition coefficients (Kp) towards lipid bilayers. Curiously, although temoporfin and redaporfin presented similar Kps, redaporfin did not present light-independent antiviral activity, and only temoporfin and verteporfin caused lipid membrane disorder. In fact, redaporfin is located closer to the bilayer surface, while temoporfin and verteporfin are located closer to the centre. Our results suggest that viral envelope affinity, with penetration and destabilization of the lipid bilayer, seems critical to mediate PDs antiviral activity. Altogether, these findings open new avenues for the off-label application of temoporfin and verteporfin in the systemic treatment of COVID-19.
