Department or Program

Biology

Abstract

Case rates of rotavirus, the leading viral cause of severe acute diarrhea in children under the age of 5, have been steadily declining in countries that have had access to effective mitigation strategies. In children experiencing nutritional insecurity, however, there is a significant decrease in vaccine efficacy. With vaccination and oral rehydration remaining the only rotavirus interventions (preventative and clinical) in place, significant inquiry is required to make antiviral treatment a reality. The NSP4 protein in rotavirus is a viroporin responsible for disturbing the stability of the rough ER membrane of epithelial cells, forming pores that disrupt calcium ion homeostasis. This viral pathway is a prime candidate for target in antiviral drug design, both because of its critical nature towards the function and replication of rotavirus and the myriad of preexisting drugs that block ordinary calcium ion channels. As the Banks lab and its collaborators continue to develop targeted antiviral drugs, an analytical review of existing, FDA-approved ion channel blockers that may cross-react with NSP4 is necessary to determine biophysical drug characteristics that are favorable for inhibiting this protein. After performing an extensive literature review, we selected amlodipine, diltiazem, and verapamil as calcium channel blockers to analyze as NSP4 antagonists. We utilized planar lipid bilayer electrophysiology to determine the binding kinetics and efficacy of selected viroporin inhibitors in lipid bilayer. In addition, we will assess the ability of computational modeling systems to confirm these findings.

Level of Access

Open Access

First Advisor

Banks, Lori

Date of Graduation

5-2023

Degree Name

Bachelor of Science

Number of Pages

45

Download

Open Access

Available to all.

Share

COinS