Extracellular and intracellular antiviral effects of ultraviolet A against severe acute respiratory syndrome coronavirus-2 are variant-independent
Gabriela Leite, Sepideh Mehravar, Mark Pimentel, Ruchi Mathur, Gil Y Melmed, Volha Teagle, Gillian M Barlow, Ali Rezaie
Photodiagnosis and Photodynamic Therapy, doi:10.1016/j.pdpdt.2024.104097
Under controlled settings, narrow-band ultraviolet A (UVA) exposure exerts antiviral effects both in vivo and in vitro. The effect is thought to be mediated via direct effect on viral particles and indirectly, by modulation of metabolic pathways of host cells. We aimed to explore the extracellular and intracellular antiviral effects of UVA exposure against Alpha, Beta, and Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: Vero E6 kidney normal epithelial cells and human tracheal epithelial cells were infected with Alpha, Beta, and Delta variants in a BSL-3 laboratory. To assess extracellular effects, SARS-CoV-2 variants were directly exposed to a single dose of UVA prior to infection of the host cells (Vero E6 kidney normal epithelial cells and human tracheal epithelial cells) The intracellular effects of UVA were assessed by first infecting the cells with SARS-CoV-2 variants followed by UVA treatment of infected cell monolayers. Efficacy was quantified by both plaque reduction assay and quantitative real-time polymerase chain reaction. Additionally, transcriptomic analysis was performed on exposed Vero E6 cells to assess differentially expressed genes and canonical pathways as compared to controls. Results: SARS-CoV-2 Alpha, Beta and Delta variants are susceptible to UVA exposure prior to infection of Vero E6 cells. Importantly, the UVA-driven reduction in Delta variant load could be reproduced in human primary tracheal cells. Beta and Delta variants load also significantly decreased during Vero E6 cells intracellular experiments. UVA-driven reductions in viral loads ameliorate several host metabolic pathways, including canonical pathways related to viral infection and interferon signaling. Conclusion: Narrow-band UVA exhibits both extracellular effects on SARS-CoV-2 viral particles and intracellular effects on infected cells with SARS-CoV-2. Efficacy appears to be variant independent.
References
Barros, Phototherapy, An. Bras. Dermatol
Cascella, Features, evaluation, and treatment of coronavirus (COVID-19)
Chiang, Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy, J. Biomed. Sci
Davies, Estimated transmissibility and impact of SARS-CoV-2 lineage B. 1.1. 7 in England, Science
Fisman, Tuite, Evaluation of the relative virulence of novel SARS-CoV-2 variants: a retrospective cohort study in Ontario, Canada, Cmaj
Hemmer, Löbermann, Reisinger, COVID-19: epidemiologie und mutationen, Der Radiologe
Hoffmann, SARS-CoV-2 variant B. 1.617 is resistant to bamlanivimab and evades antibodies induced by infection and vaccination, Cell Rep
Leite, Ultraviolet-A light increases mitochondrial anti-viral signaling protein in confluent human tracheal cells via cell-cell signaling, J. Photochem. Photobiol. B
Leite, Ultraviolet-A light increases mitochondrial anti-viral signaling protein in confluent human tracheal cells via cell-cell signaling, J. Photochem. Photobiol. B: Biology
Leite, Ultraviolet-A light reduces cellular cytokine release from human endotracheal cells infected with Coronavirus, Photodiagn. Photodyn. Ther
Mendoza, Two detailed plaque assay protocols for the quantification of infectious SARS-CoV-2, Curr. Protoc. Microbiol
Michaelsen, Introduction and transmission of SARS-CoV-2 lineage B. 1.1. 7, Alpha variant, in Denmark, Genome. Med
Mlcochova, SARS-CoV-2 B1.617.2 Delta variant replication and immune evasion, Nature
Planas, Sensitivity of infectious SARS-CoV-2 B 1.1. 7 and B. 1.351 variants to neutralizing antibodies, Nat. Med
Rezaie, Endotracheal application of ultraviolet A light in critically Ill patients with severe acute respiratory syndrome coronavirus 2: a first-in-human study, Adv. Ther
Rezaie, Ultraviolet A light effectively reduces bacteria and viruses including coronavirus, PLoS ONE
Tegally, Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa
Vitiello, Sars-Cov-2 and risk of antiviral drug resistance, Ir. J. Med. Sci
Zaki, Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia, New Engl. J. Med
Zhan, Yin, Yin, B.1.617.2 (Delta) Variant of SARS-CoV-2: features, transmission and potential strategies, Int. J. Biol. Sci
Zhang, Emergence of a novel SARS-CoV-2 variant in Southern California, JAMA
Zhou, A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature
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'antibodies induced by infection and vaccination',
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'retrospective cohort study in Ontario, Canada',
'volume': '193',
'author': 'Fisman',
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'volume': '191',
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'journal-title': 'Ir. J. Med. Sci'},
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'doi-asserted-by': 'crossref',
'DOI': '10.1371/journal.pone.0236199',
'article-title': 'Ultraviolet A light effectively reduces bacteria and viruses including '
'coronavirus',
'volume': '15',
'author': 'Rezaie',
'year': '2020',
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'article-title': 'Ultraviolet-A light reduces cellular cytokine release from human '
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'volume': '35',
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'first-in-human study',
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