Date of Award

2022

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology

Abstract

Identifying novel antivirals requires significant time and resource investment, and the continuous threat of viruses to human health necessitates commitment to antiviral identification and development. Developing antivirals requires years of research and validation, and recent outbreaks have highlighted the need for preparedness in counteracting pandemics. One way to facilitate development is to repurpose molecules already used clinically. By screening such compounds, we can accelerate antiviral development. Here, we screened compounds from the National Institutes of Health’s Developmental Therapeutic Program for activity against chikungunya virus, an alphavirus that is responsible for a significant outbreak in the Americas in 2013. Using this library, we identified several compounds with known antiviral activity, as well as several novel antivirals. Given its favorable in vitro activity and well-described in vivo activity, as well as its broad availability, we focused on bisacodyl, a laxative used for the treatment of constipation, for follow-up studies. We find that bisacodyl inhibits chikungunya virus infection in a variety of cell types, over a range of concentrations, and over several rounds of replication. We find that bisacodyl does not disrupt chikungunya virus particles or interfere with their ability to attach to cells, but instead bisacodyl inhibits virus replication. Finally, we find that bisacodyl is broadly antiviral against a variety of RNA viruses, including enteroviruses, flaviviruses, bunyaviruses, and alphaviruses; however, it exhibited no activity against the DNA virus vaccinia virus. Together, these data highlight the power of compound screening to identify novel antivirals and suggest that bisacodyl may hold promise as a broad-spectrum antiviral.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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