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Antiviral Activity of Acetylsalicylic Acid against Bunyamwera Virus in Cell Culture

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 fif...

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Autores principales: Fernández-Sánchez, Sara Yolanda, Cerón-Carrasco, José P., Risco, Cristina, Fernández de Castro, Isabel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141918/
https://www.ncbi.nlm.nih.gov/pubmed/37112928
http://dx.doi.org/10.3390/v15040948
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author Fernández-Sánchez, Sara Yolanda
Cerón-Carrasco, José P.
Risco, Cristina
Fernández de Castro, Isabel
author_facet Fernández-Sánchez, Sara Yolanda
Cerón-Carrasco, José P.
Risco, Cristina
Fernández de Castro, Isabel
author_sort Fernández-Sánchez, Sara Yolanda
collection PubMed
description 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 (IC(50)) 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.
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spelling pubmed-101419182023-04-29 Antiviral Activity of Acetylsalicylic Acid against Bunyamwera Virus in Cell Culture Fernández-Sánchez, Sara Yolanda Cerón-Carrasco, José P. Risco, Cristina Fernández de Castro, Isabel Viruses Article 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 (IC(50)) 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. MDPI 2023-04-11 /pmc/articles/PMC10141918/ /pubmed/37112928 http://dx.doi.org/10.3390/v15040948 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fernández-Sánchez, Sara Yolanda
Cerón-Carrasco, José P.
Risco, Cristina
Fernández de Castro, Isabel
Antiviral Activity of Acetylsalicylic Acid against Bunyamwera Virus in Cell Culture
title Antiviral Activity of Acetylsalicylic Acid against Bunyamwera Virus in Cell Culture
title_full Antiviral Activity of Acetylsalicylic Acid against Bunyamwera Virus in Cell Culture
title_fullStr Antiviral Activity of Acetylsalicylic Acid against Bunyamwera Virus in Cell Culture
title_full_unstemmed Antiviral Activity of Acetylsalicylic Acid against Bunyamwera Virus in Cell Culture
title_short Antiviral Activity of Acetylsalicylic Acid against Bunyamwera Virus in Cell Culture
title_sort antiviral activity of acetylsalicylic acid against bunyamwera virus in cell culture
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141918/
https://www.ncbi.nlm.nih.gov/pubmed/37112928
http://dx.doi.org/10.3390/v15040948
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