Cargando…
Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection
Venezuelan equine encephalitis virus (VEEV) is a category B select agent pathogen that can be aerosolized. Infections in murine models and humans can advance to an encephalitic phenotype which may result in long-term neurological complications or death. No specific FDA-approved treatments or vaccine...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950191/ https://www.ncbi.nlm.nih.gov/pubmed/31842327 http://dx.doi.org/10.3390/v11121151 |
_version_ | 1783486013870440448 |
---|---|
author | Risner, Kenneth Ahmed, Aslaa Bakovic, Allison Kortchak, Stephanie Bhalla, Nishank Narayanan, Aarthi |
author_facet | Risner, Kenneth Ahmed, Aslaa Bakovic, Allison Kortchak, Stephanie Bhalla, Nishank Narayanan, Aarthi |
author_sort | Risner, Kenneth |
collection | PubMed |
description | Venezuelan equine encephalitis virus (VEEV) is a category B select agent pathogen that can be aerosolized. Infections in murine models and humans can advance to an encephalitic phenotype which may result in long-term neurological complications or death. No specific FDA-approved treatments or vaccines are available for the treatment or prevention of VEEV infection. Neurotropic viral infections have two damaging components: neuronal death caused by viral replication, and damage from the subsequent inflammatory response. Reducing the level of inflammation may lessen neurological tissue damage that often arises following VEEV infection. In this study, three commercially available anti-inflammatory drugs, Celecoxib, Rolipram, and Tofacitinib, were evaluated for antiviral activity in an astrocyte and a microglial model of VEEV infection. The inhibitors were tested against the vaccine strain VEEV TC-83, as well as the wild-type VEEV Trinidad donkey strain. Celecoxib, Tofacitinib, and Rolipram significantly decreased viral titers both after pre-treatment and post-treatment of infected cells. VEEV Trinidad Donkey (TrD) titers were reduced 6.45-fold in cells treated with 50 µM of Celecoxib, 2.45-fold when treated with 50 µM of Tofacitinib, and 1.81-fold when treated with 50 µM of Rolipram. Celecoxib was also shown to decrease inflammatory gene expression in the context of TC-83 infection. Overall, Celecoxib demonstrated potency as a countermeasure strategy that slowed VEEV infection and infection-induced inflammation in an in vitro model. |
format | Online Article Text |
id | pubmed-6950191 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69501912020-01-16 Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection Risner, Kenneth Ahmed, Aslaa Bakovic, Allison Kortchak, Stephanie Bhalla, Nishank Narayanan, Aarthi Viruses Article Venezuelan equine encephalitis virus (VEEV) is a category B select agent pathogen that can be aerosolized. Infections in murine models and humans can advance to an encephalitic phenotype which may result in long-term neurological complications or death. No specific FDA-approved treatments or vaccines are available for the treatment or prevention of VEEV infection. Neurotropic viral infections have two damaging components: neuronal death caused by viral replication, and damage from the subsequent inflammatory response. Reducing the level of inflammation may lessen neurological tissue damage that often arises following VEEV infection. In this study, three commercially available anti-inflammatory drugs, Celecoxib, Rolipram, and Tofacitinib, were evaluated for antiviral activity in an astrocyte and a microglial model of VEEV infection. The inhibitors were tested against the vaccine strain VEEV TC-83, as well as the wild-type VEEV Trinidad donkey strain. Celecoxib, Tofacitinib, and Rolipram significantly decreased viral titers both after pre-treatment and post-treatment of infected cells. VEEV Trinidad Donkey (TrD) titers were reduced 6.45-fold in cells treated with 50 µM of Celecoxib, 2.45-fold when treated with 50 µM of Tofacitinib, and 1.81-fold when treated with 50 µM of Rolipram. Celecoxib was also shown to decrease inflammatory gene expression in the context of TC-83 infection. Overall, Celecoxib demonstrated potency as a countermeasure strategy that slowed VEEV infection and infection-induced inflammation in an in vitro model. MDPI 2019-12-12 /pmc/articles/PMC6950191/ /pubmed/31842327 http://dx.doi.org/10.3390/v11121151 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Risner, Kenneth Ahmed, Aslaa Bakovic, Allison Kortchak, Stephanie Bhalla, Nishank Narayanan, Aarthi Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection |
title | Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection |
title_full | Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection |
title_fullStr | Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection |
title_full_unstemmed | Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection |
title_short | Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection |
title_sort | efficacy of fda-approved anti-inflammatory drugs against venezuelan equine encephalitis virus infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950191/ https://www.ncbi.nlm.nih.gov/pubmed/31842327 http://dx.doi.org/10.3390/v11121151 |
work_keys_str_mv | AT risnerkenneth efficacyoffdaapprovedantiinflammatorydrugsagainstvenezuelanequineencephalitisvirusinfection AT ahmedaslaa efficacyoffdaapprovedantiinflammatorydrugsagainstvenezuelanequineencephalitisvirusinfection AT bakovicallison efficacyoffdaapprovedantiinflammatorydrugsagainstvenezuelanequineencephalitisvirusinfection AT kortchakstephanie efficacyoffdaapprovedantiinflammatorydrugsagainstvenezuelanequineencephalitisvirusinfection AT bhallanishank efficacyoffdaapprovedantiinflammatorydrugsagainstvenezuelanequineencephalitisvirusinfection AT narayananaarthi efficacyoffdaapprovedantiinflammatorydrugsagainstvenezuelanequineencephalitisvirusinfection |