Trifluridine for treatment of mpox infection in drug combinations in ophthalmic cell models.

Autor: Cinatl J; Institute of Medical Virology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.; Dr. Petra Joh-Forschungshaus, Frankfurt am Main, Germany., Bechtel M; Institute of Medical Virology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany., Reus P; Institute of Medical Virology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.; Discovery Research ScreeningPort, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Hamburg, Germany., Ott M; Dr. Petra Joh-Forschungshaus, Frankfurt am Main, Germany., Rothweiler F; Dr. Petra Joh-Forschungshaus, Frankfurt am Main, Germany., Michaelis M; Dr. Petra Joh-Forschungshaus, Frankfurt am Main, Germany.; School of Biosciences, University of Kent, Canterbury, UK., Ciesek S; Institute of Medical Virology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.; German Center for Infection Research, DZIF, External Partner Site, Frankfurt am Main, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany., Bojkova D; Institute of Medical Virology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.
Jazyk: angličtina
Zdroj: Journal of medical virology [J Med Virol] 2024 Jan; Vol. 96 (1), pp. e29354.
DOI: 10.1002/jmv.29354
Abstrakt: The Mpox virus can cause severe disease in the susceptible population with dermatologic and systemic manifestations. Furthermore, ophthalmic manifestations of mpox infection are well documented. Topical trifluridine (TFT) eye drops have been used for therapy of ophthalmic mpox infection in patients, however, its efficacy against mpox virus infection in this scenario has not been previously shown. In the present study, we have established ophthalmic cell models suitable for the infection with mpox virus. We show, that TFT is effective against a broad range of mpox isolates in conjunctival epithelial cells and keratocytes. Further, TFT remained effective against a tecovirimat-resistant virus strain. In the context of drug combinations, a nearly additive effect was observed for TFT combinations with brincidofovir and tecovirimat in conjunctival epithelial cells, while a slight antagonism was observed for both combinations in keratocytes. Altogether, our findings demonstrate TFT as a promising drug for treatment of ophthalmic mpox infection able to overcome tecovirimat resistance. However, conflicting results regarding the effect of drug combinations with approved compounds warrant close monitoring of such use in patients.
(© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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