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Home / Equine Research Bank / Viruses / Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Ven...
Viruses2019; 11(12); 1151; doi: 10.3390/v11121151

Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection.

Abstract: 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.
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Publication Date: 2019-12-12 PubMed ID: 31842327PubMed Central: PMC6950191DOI: 10.3390/v11121151Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigated the potential of three commercially available anti-inflammatory drugs (Celecoxib, Rolipram, and Tofacitinib) to treat infection caused by the Venezuelan Equine Encephalitis Virus (VEEV). The study found that all three drugs were able to significantly reduce viral activity in the tested cells and that Celecoxib also reduced virus-induced inflammation.

Research Objectives and Context

  • The research team set out to investigate potential treatments for Venezuelan Equine Encephalitis Virus, a potentially deadly airborne pathogen for which there are currently no specific approved treatments or vaccines. They focused on the potential of anti-inflammatory drugs to reduce the neurological tissue damage that often results from VEEV infection.
  • VEEV infection is typically characterized by two stages of damage: neuronal cell death due to viral replication, and further damage resulting from a subsequent inflammatory response by the neural tissue.
  • While there are no approved treatments to directly combat VEEV, the researchers hypothesized that reducing post-infection inflammation could mitigate some of the neurological tissue damage.

Research Methods and Drug Selection

  • The research assessed the efficacy of Celecoxib, Rolipram, and Tofacitinib – anti-inflammatory drugs that are already FDA-approved for other uses – in an astrocyte (a cell in the brain) and a microglial (a type of immune cell in the nervous system) model of VEEV infection.
  • The testing was carried out on both the TC-83 vaccine strain of VEEV, as well as the wild-type VEEV Trinidad donkey strain.

Research Findings

  • All three tested drugs were found to significantly reduce viral activity in cells, both when administered before and after infection took place.
  • Among the three, Celecoxib proved to be especially effective, reducing viral titers by a factor of 6.45 when administered at a concentration of 50 µM. Tofacitinib and Rolipram achieved reductions of 2.45-fold and 1.81-fold respectively under the same conditions.
  • Beyond reducing viral activity, Celecoxib was also observed to decrease inflammatory gene expression in the context of TC-83 infection.

Conclusion and Implications

  • While more research would be needed to confirm these results, this study indicates that the three drugs tested – and Celecoxib in particular – have the potential to be used as countermeasures against VEEV infection.
  • The ability of these drugs to significantly lower viral activity and inflammation in cells could mitigate some of the damaging effects of the virus, potentially reducing the severity of symptoms in infected individuals.

Cite This Article

APA
Risner K, Ahmed A, Bakovic A, Kortchak S, Bhalla N, Narayanan A. (2019). Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection. Viruses, 11(12), 1151. https://doi.org/10.3390/v11121151

Publication

Viruses
ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 11
Issue: 12
PII: 1151

Researcher Affiliations

Risner, Kenneth
  • National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA.
Ahmed, Aslaa
  • National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA.
Bakovic, Allison
  • National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA.
Kortchak, Stephanie
  • National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA.
Bhalla, Nishank
  • National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA.
Narayanan, Aarthi
  • National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA.

MeSH Terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antiviral Agents / pharmacology
  • Astrocytes / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Drug Approval
  • Drug Repositioning
  • Encephalitis Virus, Venezuelan Equine / drug effects
  • Encephalomyelitis, Venezuelan Equine / drug therapy
  • Encephalomyelitis, Venezuelan Equine / virology
  • Humans
  • Microglia / drug effects
  • United States
  • United States Food and Drug Administration
  • Virus Replication / drug effects

Conflict of Interest Statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Citations

This article has been cited 13 times.
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