Verteporfin is an effective inhibitor of HCMV replication
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Human cytomegalovirus (HCMV), a double-stranded DNA virus from the Betaherpesvirinae subfamily, constitutes significant risks to newborns and immunocompromised individuals, potentially leading to severe neurodevelopmental disorders. The purpose of this study was to identify FDA-approved drugs that can inhibit HCMV replication through a drug repositioning approach. Using an HCMV progeny assay, verteporfin, a medication used as a photosensitizer in photodynamic therapy, was found to inhibit HCMV production in a dose-dependent manner, significantly reducing replication at concentrations as low as 0.5 µM, approximately 1/20th of the concentration used in anti-cancer research. Further analysis revealed that verteporfin did not interfere with HCMV host cell entry or nuclear transport but reduced viral mRNA and protein levels throughout the HCMV life cycle from the immediate-early stages. These results suggest that verteporfin has the potential to be rapidly and safely developed as a repurposed drug to inhibit HCMV infection.Keywords:
Verteporfin
Drug repositioning
Photodynamic therapy (PDT) is a phototherapy in which a photosensitive dye is injected into a peripheral vein and activated by light in order to occlude choroidal vessels or change their permeability. PDT has been largely applied in the treatment of choroidal neovascularization (CNV), especially CNV related to age-related macular degeneration, but was also of benefit in other diseases, including central serous chorioretinopathy and choroidal hemangioma.
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This study aimed to describe the effects of no-dose full-fluence photodynamic therapy without verteporfin (no-dose PDT) and to compare no-dose PDT with half-dose verteporfin full-fluence photodynamic therapy (HDFF PDT) for managing chronic central serous chorioretinopathy (cCSC).This retrospective study evaluated 11 patients with chronic recurrent CSC treated with no-dose PDT between January 2019 and March 2022. Most of these patients were also treated with HDFF PDT a minimum of 3 months before and were considered as the control group. We described the changes of best corrected visual acuity (BCVA), maximum subretinal fluid (mSRF), foveal subretinal fluid (fSRF), and choroidal thickness (CT) 8 ± 2 weeks after no-dose PDT, and we compared BVCA, mSRF, fSRF, and CT of no-dose PDT with those of the of same patients previously treated with HDFF PDT.Fifteen eyes of 11 patients (10 male, mean age 54 ± 12 years) received no-dose PDT; among these, 10 eyes of 8 patients (7 male, mean age 53 ± 12 years) also received HDFF PDT. Three eyes showed complete resolution of fSRF after no-dose PDT. No significant differences were disclosed between treatment with and without verteporfin comparing BCVA, mSRF, fSRF, and CT at baseline and 8 ± 2 weeks from the treatment (p > 0.05 in all analyses).BVCA and CT significantly improved after no-dose PDT. Short-term functional and anatomical treatment outcomes for cCSC were similar for HDFF PDT and no-dose PDT. We hypothesize that the potential benefits of no-dose PDT may arise from thermal elevation that triggers and enhances photochemical activities by endogenous fluorophores, activating a biochemical cascade response that rescues/replaces sick, dysfunctional retinal pigment epithelial (RPE) cells. Results of this study suggest the potential value of a prospective clinical trial to evaluate no-dose PDT for managing cCSC, especially when verteporfin is contraindicated or unavailable.
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Photodynamic therapy: Dermatology and ophthalmology as main fields of current applications in clinic
Photodynamic therapy (PDT) of skin tumors or pre-cancerous lesions and of age-related macular degeneration combines the administration of porphyrins or porphyrin precursors and illumination with red light at the diseased sites. Photosensitizers absor
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Abstract Objective To describe the effects of no-dose full fluence photodynamic therapy without verteporfin (no-dose PDT) and to compare no-dose PDT with half-dose verteporfin full-fluence photodynamic therapy (HDFF PDT) for managing chronic central serous chorioretinopathy (cCSC). Methods This retrospective study evaluated 11 patients with chronic recurrent CSC treated with no-dose PDT between January 2019 and March 2022. Most of these patients were also treated with half-dose full-fluence PDT (HDFF PDT) a minimum of 3- months before and were considered as control group. We described the changes of best-corrected visual acuity (BCVA), maximum subretinal fluid (mSRF), foveal subretinal fluid (fSRF) and choroidal thickness (CT) 8 ± 2 weeks after no-dose PDT, and we compared BVCA, mSRF, fSRF and CT of no-dose PDT with those of the of same patients previously treated with HDFF PDT. Results Fifteen eyes of 11 patients (10 males, mean age 54 ± 12 years) received no-dose PDT; among these, 10 eyes of 8 patients (7 males, mean age 53 ± 12 years) received also HDFF PDT. Three eyes showed complete resolution of fSRF after no-dose PDT. No significant differences were disclosed between treatment with and without verteporfin comparing BCVA, mSRF, fSRF, and CT at the baseline and 8 ± 2 weeks from the treatment (p > 0.05 in all analyses). Conclusion BVCA and CT significantly improved after no-dose PDT. Short-term functional and anatomical treatment outcomes for cCSC were similar for HDFF PDT and no-dose PDT. We hypothesize that the potential benefits of no-dose PDT may arise thermal elevation triggers and enhances photochemical activities by endogenous fluorophores that activates a biochemical cascade response that rescues / replaces sick, dysfunctional RPE cells. Results of this study suggest the potential value of a prospective clinical trial to evaluate no-dose PDT for managing cCSC, especially when verteporfin is contraindicated or unavailable.
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Purpose To report a case of photodynamic therapy (PDT) treatment in an 85-year-old patient with retinal angiomatous proliferation (RAP) stage I. Methods According to Treatment of Age-Related Macular Degeneration with Photodynamic Therapy and Verteporfin in Photodynamic Therapy study guidelines, two sessions of PDT with verteporfin were performed, which was activated by a diode laser light at 690 nm. Results The left eye was treated with PDT because of RAP stage I. Even in the early stage of RAP, PDT treatment did not alter the natural course of the disease. In particular, the lesion evolved towards stage III, being initially in stage I, with the final result of development of retinal pigment epithelial (RPE) tear after the second session of PDT treatment. Conclusions Even in the early stage of RAP, PDT treatment did not alter the natural course of the disease, with the final result of RPE tear after the second session of PDT treatment.
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Wet age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. Verteporfin photodynamic therapy (PDT) is significantly effective in preventing visual loss in patients with subfoveal choroidal neovascularization caused by exudative AMD. This article reviews verteporfin PDT and discusses treatment and evolving appraisal guidance.
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