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Título: | Antiviral Activity of Acetylsalicylic Acid against Bunyamwera Virus in Cell Culture |
Autor: | Fernández-Sánchez, Sara Yolanda; Cerón-Carrasco, José P.; Risco, Cristina; Fernández de Castro, Isabel | Palabras clave: | Bunyavirus Bunyamwera virus Viral RNA polymerase Viral replication organelle Acetylsalicylic acid (ASA) Antiviral High-throughput screening Molecular modeling Drug repurposing Electron microscopy |
Fecha de publicación: | 11-abr-2023 | Editor: | Multidisciplinary Digital Publishing Institute | Citación: | Viruses 15(4): 948 (2023) | Resumen: | The Bunyavirales order is a large group of RNA viruses that includes important pathogens for humans, animals and plants. With high-throughput screening of clinically tested compounds we have looked for potential inhibitors of the endonuclease domain of a bunyavirus RNA polymerase. From a list of fifteen top candidates, five compounds were selected and their antiviral properties studied with Bunyamwera virus (BUNV), a prototypic bunyavirus widely used for studies about the biology of this group of viruses and to test antivirals. Four compounds (silibinin A, myricetin, L-phenylalanine and p-aminohippuric acid) showed no antiviral activity in BUNV-infected Vero cells. On the contrary, acetylsalicylic acid (ASA) efficiently inhibited BUNV infection with a half maximal inhibitory concentration (IC50) of 2.02 mM. In cell culture supernatants, ASA reduced viral titer up to three logarithmic units. A significant dose-dependent reduction of the expression levels of Gc and N viral proteins was also measured. Immunofluorescence and confocal microscopy showed that ASA protects the Golgi complex from the characteristic BUNV-induced fragmentation in Vero cells. Electron microscopy showed that ASA inhibits the assembly of Golgi-associated BUNV spherules that are the replication organelles of bunyaviruses. As a consequence, the assembly of new viral particles is also significantly reduced. Considering its availability and low cost, the potential usability of ASA to treat bunyavirus infections deserves further investigation. | Versión del editor: | https://doi.org/10.3390/v15040948 | URI: | http://hdl.handle.net/10261/308092 | DOI: | 10.3390/v15040948 | E-ISSN: | 1999-4915 |
Aparece en las colecciones: | (CNB) Artículos |
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viruses-15-00948-v2.pdf | 7,81 MB | Adobe PDF | Visualizar/Abrir |
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