Department or Program

Biochemistry

Abstract

COVID-19, or SARS-CoV-2, is a highly contagious respiratory coronavirus that has caused many societal changes and social unrest over the past four years. An essential feature of the virus is how rapidly it mutates, subverting current treatments. As such, new antiviral compounds must be identified to try and keep up with the quick mutation rate. The initiation of the COVID-19 infection cycle was identified as a potential target. This is because the interaction is extracellular, meaning an inhibitor would not need to be transported into the cell to be effective. One class of compounds that have shown potential as antivirals are phenylpropanoid glycosides (PPGs), common secondary metabolites in various plant species that exhibit wide-ranging in vivo effects. We set out to examine the antiviral effects of caffeoyl-based PPGs, characterized by caffeic acid (CA) groups conjugated to glucose. Preliminary data shows that CA is capable of inhibiting the extracellular interaction of the COVID-19 spike protein and the human ACE-2 receptor at sufficiently high concentrations. Building off these data, we synthesized, characterized, and tested a library of compounds utilizing a synthetic PPG scaffold appended with varying numbers of caffeoyl groups. Using a spike-ACE2 binding assay, it was determined that each of the eight compounds synthesized effectively inhibited the spike-ACE2 interaction at 500 μM, each inhibiting the interaction near 100%. The best inhibitors were determined to be methyl-2-O-caffeoyl-α-D-glucopyranoside and methyl-2,3,4-O-caffeoyl-6-O-acetyl-α-D-glucopyranoside, which are believed to inhibit the interaction through different mechanisms due to their significant structural differences.

Level of Access

Open Access

First Advisor

Koviach-Cote, Jennifer

Second Advisor

O'Loughlin, Colleen

Date of Graduation

5-2024

Degree Name

Bachelor of Science

Number of Pages

83

Components of Thesis

1 pdf

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