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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10141918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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