Uso de ganciclovir 0,15% gel para tratamento de ceratoconjuntivite adenoviral

Yabiku, Simone Tiemi; Yabiku, Mariann Midori; Bottós, Kátia Mantovani; Araújo, Aline Lütz de; Freitas, Denise de; Belfort, Rubens

doi:10.1590/s0004-27492011000600007

Cited by 25 publications

(7 citation statements)

References 23 publications

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“…One research group working in the cotton rat eye model reported that 3% GCV reduced Ad5 replication and pathology (23). In a published clinical study, treatment with 0.15% GCV ophthalmic gel improved the outcome of Ad conjunctivitis (49 In the present report, we have demonstrated that systemically administered GCV mitigates the effects of generalized Ad5 infection in immunosuppressed Syrian hamsters ( Fig. 1 and 2).…”

Section: Discussionsupporting

confidence: 63%

Ganciclovir Inhibits Human Adenovirus Replication and Pathogenicity in Permissive Immunosuppressed Syrian Hamsters

Bai

Tollefson

Spencer

et al. 2014

Antimicrob Agents Chemother

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Adenovirus infections of immunocompromised patients can develop into deadly multiorgan or systemic disease. The virus is especially threatening for pediatric allogeneic hematopoietic stem cell transplant recipients; according to some studies, 10% or more of these patients succumb to disease resulting from adenovirus infection. At present, there is no drug approved for the treatment or prevention of adenovirus infections. Compounds that are approved to treat other virus infections are used off-label to combat adenovirus, but only anecdotal evidence of the efficacy of these drugs exists. Ganciclovir, a drug approved for the treatment of herpesvirus infection, was previously reported to be effective against human adenoviruses in vitro. To model adenovirus infections in immunocompromised humans, we examined ganciclovir's efficacy in immunosuppressed Syrian hamsters intravenously infected with type 5 human adenovirus (Ad5). This animal model is permissive for Ad5 replication, and the animals develop symptoms similar to those seen in humans. We demonstrate that ganciclovir suppresses Ad5 replication in the liver of infected hamsters and that it mitigates the consequences of Ad5 infections in these animals when administered prophylactically or therapeutically. We show that ganciclovir inhibits Ad5 DNA synthesis and late gene expression. The mechanism of action for the drug is not clear; preliminary data suggest that it exerts its antiadenoviral effect by directly inhibiting the adenoviral DNA polymerase. While more extensive studies are required, we believe that ganciclovir is a promising drug candidate to treat adenovirus infections. Brincidofovir, a drug with proven activity against Ad5, was used as a positive control in the prophylactic experiment.

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Section: Discussionsupporting

confidence: 63%

Ganciclovir Inhibits Human Adenovirus Replication and Pathogenicity in Permissive Immunosuppressed Syrian Hamsters

Bai

Tollefson

Spencer

et al. 2014

Antimicrob Agents Chemother

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“…In a double blind, interventional and randomized clinical trial [ 44 ], 33 individuals with adenoviral conjunctivitis who had symptoms for five days or fewer were randomly divided in two groups: group 1 (treatment) with 19 subjects using ganciclovir gel and group 2 (control) with 14 individuals treated with preservative free artificial tears. Group 1 showed a not statistically significant tendency of better and quicker answer in terms of signs and symptoms compared with group 2.…”

Section: Resultsmentioning

confidence: 99%

Antiviral Drugs in Adenovirus-Induced Keratoconjunctivitis

2022

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Human adenovirus (HAdV) is one of the most common causes of conjunctivitis worldwide. Depending on specific serotypes and other factors, it can lead to several ocular manifestations, ranging from isolated, self-limited disease to epidemic and potentially sight-threatening keratoconjunctivitis. To date, no antiviral agent against ocular adenovirus has been licensed, and its management is still based on hygienic and supportive measures alone. In this review, a literature search up to August 2021 was performed to find peer-reviewed articles, with the primary aim to investigate drugs or other compounds with any antiviral activity against adenovirus. Finally, we included 70 articles, consisting of both in vitro, and in vivo studies on animal models and clinical trials of any phase, as well as a case-report, and analyzed each compound separately. Many antiviral agents proved to be effective on in vivo and in vitro studies on animal models, and in pre-clinical trials, but lacked reliability in large, controlled clinical investigations. The design of such studies, though, presented several hurdles, due to the nature and the specific characteristics of adenovirus-induced ocular diseases. Nevertheless, some promising compounds are currently under study, and further investigations are needed to prove their efficacy in the management of adenovirus conjunctivitis.

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“…We have shown previously that GCV, the parental drug of VGCV, was active against Ad infection in hamsters, and there is anecdotal clinical evidence that GCV may be effective against Ad infection and pathogenesis in transplant patients [ 30 , 31 , 32 , 33 , 34 , 35 ]. In addition, treatment with 0.15% GCV ophthalmic gel improved the outcome of Ad conjunctivitis [ 36 ]. It seems reasonable that if GCV can be effective in the clinic, that VGCV should be effective as well.…”

Section: Discussionmentioning

confidence: 99%

Valganciclovir Inhibits Human Adenovirus Replication and Pathology in Permissive Immunosuppressed Female and Male Syrian Hamsters

Tóth

Bai

Tollefson

et al. 2015

Viruses

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Adenovirus infections of immunocompromised pediatric hematopoietic stem cell transplant patients can develop into serious and often deadly multi-organ disease. There are no drugs approved for adenovirus infections. Cidofovir (an analog of 2-deoxycytidine monophosphate) is used at times but it can be nephrotoxic and its efficacy has not been proven in clinical trials. Brincidofovir, a promising lipid-linked derivative of cidofovir, is in clinical trials. Ganciclovir, an analog of 2-deoxyguanosine, has been employed occasionally but with unknown efficacy in the clinic. In this study, we evaluated valganciclovir against disseminated adenovirus type 5 (Ad5) infection in our permissive immunosuppressed Syrian hamster model. We administered valganciclovir prophylactically, beginning 12 h pre-infection or therapeutically starting at Day 1, 2, 3, or 4 post-infection. Valganciclovir significantly increased survival, reduced viral replication in the liver, and mitigated the pathology associated with Ad5 infection. In cultured cells, valganciclovir inhibited Ad5 DNA replication and blocked the transition from early to late stage of infection. Valganciclovir directly inhibited Ad5 DNA polymerase in vitro, which may explain, at least in part, its mechanism of action. Ganciclovir and valganciclovir are approved to treat infections by certain herpesviruses. Our results support the use of valganciclovir to treat disseminated adenovirus infections in immunosuppressed patients.

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Uso de ganciclovir 0,15% gel para tratamento de ceratoconjuntivite adenoviral

Cited by 25 publications

References 23 publications

Ganciclovir Inhibits Human Adenovirus Replication and Pathogenicity in Permissive Immunosuppressed Syrian Hamsters

Ganciclovir Inhibits Human Adenovirus Replication and Pathogenicity in Permissive Immunosuppressed Syrian Hamsters

Antiviral Drugs in Adenovirus-Induced Keratoconjunctivitis

Valganciclovir Inhibits Human Adenovirus Replication and Pathology in Permissive Immunosuppressed Female and Male Syrian Hamsters

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