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Chandrashekhar Devidas Patil, Rahul K Suryawanshi, Lulia Koujah, Deepak Shukla; Antiviral efficacy of prodigiosin against corneal herpes simplex virus infection. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2982.
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Nucleoside analogs commonly prescribed to control herpes simplex virus type-1 (HSV-1) infection of the eye. However, new non-nucleoside drugs with new targets in HSV-1 lifecycle are required to combat resistance development against existing drugs. Prodigiosin (PG) is a natural red pigment produced as a secondary metabolite by numerous bacterial species. Bacterial prodigiosin displays proapoptotic anticancer properties and exhibits cellular targets affecting the outcome of multiple pathways including NF-kB, PI3K/Akt and Wnt/b-catenin pathways. Considering its evident role in regulating unnatural cell survival, we sought to investigate the previously unknown benefits of prodigiosin on ocular HSV-1 infection.
Using human corneal epithelial (HCE) cells as a physiologically relevant in vitro model, the therapeutic potential of PG was determined by assessing levels of HSV-1 gene transcripts and proteins by qRT-PCR and western blot analysis, respectively. The effect of PG therapy on the formation of mature virus particles was quantified by plaque assay, which indicates the number of plaque-forming units. In vivo and ex vivo studies were performed using balb/c mice and porcine corneas. Also, the therapeutic mechanism of PG was investigated using western blot analysis, plasmid transfection, qRT-PCR and Annexin-V-FITC/PI.
In-vitro and Ex-vivo studies showed suppression of HSV-1 replication with treatment of PG in a dose-dependent manner, displaying an optimal therapeutic concentration of 2.5µM. Similarly In-vivo ocular infection of HSV-1 was profoundly less with topical treatment of PG treatment and protective against disease development. Histological sections of cornea showed no inflammation of epithelial layers with PG treatment compared to DMSO and the conservation of corneal integrity. Mechanistic studies reveled inhibition of proviral host factors including NFkB and protein kinase B (AKT) in PG treatment group.
Here we report PG as a novel antiviral agent against ocular HSV-1 infection. By blocking the dysregulation of multiple signaling pathways during infection, PG acts on host machinery to attenuate viral replication and disease progression.
This is a 2020 ARVO Annual Meeting abstract.
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