Selective, broad-spectrum antiviral photodynamic disinfection with dicationic imidazolyl chlorin photosensitizers

Photochem Photobiol Sci. 2023 Nov;22(11):2607-2620. doi: 10.1007/s43630-023-00476-4. Epub 2023 Sep 11.

Abstract

The COVID-19 pandemic exposes our vulnerability to viruses that acquire the ability to infect our cells. Classical disinfection methods are limited by toxicity. Existing medicines performed poorly against SARS-CoV-2 because of their specificity to targets in different organisms. We address the challenge of mitigating known and prospective viral infections with a new photosensitizer for antimicrobial photodynamic therapy (aPDT). Photodynamic inactivation is based on local oxidative stress, which is particularly damaging to enveloped viruses. We synthesized a cationic imidazolyl chlorin that reduced by > 99.999% of the percentage inhibition of amplification of SARS-CoV-2 collected from patients at 0.2 µM concentration and 4 J cm-2. Similar results were obtained in the prevention of infection of human ACE2-expressing HEK293T cells by a pseudotyped lentiviral vector exhibiting the S protein of SARS-CoV-2 at its surface. No toxicity to human epidermal keratinocytes (HaCaT) cells was found under similar conditions. aPDT with this chlorin offers fast and safe broad-spectrum photodisinfection and can be repeated with low risk of resistance.

Keywords: Chlorins; Photodynamic inactivation; Photodynamic therapy; Pseudotyped lentiviral vector; Reactive oxygen species; SARS-CoV-2.

MeSH terms

  • Anti-Infective Agents*
  • Antiviral Agents / pharmacology
  • Disinfection
  • HEK293 Cells
  • Humans
  • Pandemics
  • Photochemotherapy* / methods
  • Photosensitizing Agents / chemistry
  • Prospective Studies
  • SARS-CoV-2

Substances

  • Photosensitizing Agents
  • chlorin
  • Anti-Infective Agents
  • Antiviral Agents