Identification of Small Molecule Inhibitors for Anti-Zika Infection by Targeting RNA Polymerase

Authors

Thao Nghiem, University of Nebraska - LincolnFollow

First Advisor

Shi-Hua Xiang

Date of this Version

Spring 4-14-2025

Document Type

Thesis

Citation

Nghiem, T. 2025. Identification of Small Molecule Inhibitors for Anti-Zika Infection by Targeting RNA Polymerase. Undergraduate Honors Thesis. University of Nebraska-Lincoln.

Comments

Copyright Thao Nghiem 2025.

Abstract

Zika virus (ZIKV) remains a significant global health concern with no approved antiviral treatment currently available. This study aimed to identify potential ZIKV antiviral compounds through in vitro approaches. Twelve analogues of OFB3, a benzothiophene-derived compound previously shown to inhibit Flavivirus RNA-dependent RNA polymerase (RdRp), were selected for testing on Vero-E6 cells. Of these, four compounds—OFB3-7, OFB3-9, OFB3-10, and OFB3-11—demonstrated strong antiviral activity and low cytotoxicity in Vero-E6 cells. CC₅₀ analyses confirmed minimal toxicity for OFB3-7 and OFB3-10, while OFB3-9 and OFB3-11 showed slightly higher but still acceptable toxicity profiles. Although IC₅₀ values are still being determined, currently available data indicate that these four compounds hold promise as effective and safe ZIKV antivirals. Ongoing experiments, including plaque assays and comparisons with the control compound Remdesivir, will further evaluate their antiviral potential. These findings contribute to the ongoing search for viable antiviral candidates against ZIKV.