Department or Program

Biology

Abstract

Rotavirus is the leading cause of severe dehydration and gastroenteritis worldwide for children under the age of five. While multiple vaccines for the disease are commercially available, inaccessibility continues to be a major obstacle for economically disadvantaged or underdeveloped regions. Viroporins have become a prime target for drug development in various infections due to their critical role in facilitating ion exchange across lipid membranes, impacting the signal transduction for a multitude of viral and host cellular pathways. No studies to date have been published determining the impact of viroporin inhibition as a treatment for rotavirus. This project investigates the potential of the antiviral ion channel inhibitors azelnidipine, rimantadine hydrochloride, and 5-(N,N-hexamethylene)amiloride for their ability to bind and inhibit the activity of the virally encoded ion channel Non-structural protein 4 (NSP4) in rotavirus. The conducted experiments address three major aims; I) Determine the toxicity of inhibitors using the E. coli assay, II) Determine the IC50 of inhibitors using the E. coli assay, and III) Determine binding kinetics of inhibitors using thermofluor assay. While it was hypothesized that conditions treated with azelnidipine would be the most effective inhibitor of NSP4, we found that azelnidipine, rimantadine hydrochloride, and 5-(N,N-hexamethylene)amiloride were all unable to decrease cell lysis due to NSP4 expression. Ongoing experiments are exploring thermofluor assay and patch clamp techniques to determine ion channel conductivity of activated NSP4.

Level of Access

Restricted: Campus/Bates Community Only Access

First Advisor

Banks, Lori

Date of Graduation

5-2022

Degree Name

Bachelor of Science

Number of Pages

39

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