2. Academic Validation
  3. Repurposing anti-cancer porphyrin derivative drugs to target SARS-CoV-2 envelope

Repurposing anti-cancer porphyrin derivative drugs to target SARS-CoV-2 envelope

  • Biomed Pharmacother. 2024 May 24:176:116768. doi: 10.1016/j.biopha.2024.116768.
Diogo A Mendonça 1,  Iris Cadima-Couto 1,  Carolina C Buga 2,  Zoe A Arnaut 3,  Fabio A Schaberle 4,  Luis G Arnaut 4,  Miguel A R B Castanho 5,  Christine Cruz-Oliveira 6
Affiliations

Affiliations

  • 1 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal.
  • 2 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, Oeiras 2780-157, Portugal.
  • 3 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal; CQC-IMS, Chemistry Department, University of Coimbra, Coimbra 3004-535, Portugal.
  • 4 CQC-IMS, Chemistry Department, University of Coimbra, Coimbra 3004-535, Portugal.
  • 5 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal. Electronic address: macastanho@medicina.ulisboa.pt.
  • 6 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal. Electronic address: christine.oliveira@medicina.ulisboa.pt.
PMID: 38795638 DOI: 10.1016/j.biopha.2024.116768
Abstract

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.

Keywords

Antiviral agents; Membrane targeting; Porphyrin derivatives; SARS-CoV-2; Temoporfin; Verteporfin.

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