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RNA Interference

RNA Interference

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Using Click Chemistry to Measure the Effect of Viral Infection on Host-Cell RNA Synthesis

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Metal coordinating inhibitors of Rift Valley fever virus replication.

Elizabeth Geerling¹, Valerie Murphy¹, Maria C Mai¹

¹Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America.

|September 16, 2022

Summary

New antiviral compounds targeting Rift Valley fever virus (RVFV) and La Crosse virus (LACV) have been identified. These novel inhibitors, primarily α-Hydroxytropolones and N-Hydroxypyridinediones, show promise for treating these serious viral infections.

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Last Updated: Aug 28, 2025

Using Click Chemistry to Measure the Effect of Viral Infection on Host-Cell RNA Synthesis

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Using Reverse Genetics to Manipulate the NSs Gene of the Rift Valley Fever Virus MP-12 Strain to Improve Vaccine Safety and Efficacy

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High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication

Published on: October 30, 2021

Area of Science:

Virology
Drug Discovery
Infectious Diseases

Background:

Rift Valley fever virus (RVFV) is a significant veterinary and human pathogen with bioterrorism implications.
Current RVFV treatment options are limited to supportive care, highlighting the urgent need for novel antiviral therapies.
RVFV replication relies on the viral L protein, a potential target for therapeutic intervention.

Purpose of the Study:

To identify novel inhibitors of Rift Valley fever virus (RVFV) replication.
To explore compounds with divalent cation-coordinating motifs as potential antiviral agents.
To evaluate the efficacy and specificity of identified inhibitors against Bunyavirales and related viruses.

Main Methods:

Screening of compounds with motifs similar to viral nuclease inhibitors.
In vitro antiviral assays using Vero and A549 cell lines to determine 50% effective concentrations (EC50) and selective indexes (SI).
Cross-reactivity testing against La Crosse Virus (LACV) and Zika virus (ZIKV) to assess specificity.

Main Results:

Identification of 47 novel RVFV inhibitors, predominantly α-Hydroxytropolones and N-Hydroxypyridinediones.
Inhibitors demonstrated selective indexes ranging from 1.1 to 103 and EC50 values between 1.2–56 μM in Vero cells.
Activity was validated in human A549 cells, and select compounds showed cross-reactivity against LACV.

Conclusions:

α-Hydroxytropolone and N-Hydroxypyridinedione chemotypes are promising scaffolds for developing therapeutics against RVFV and LACV.
Further investigation into the mechanism of action of these compounds is warranted.
Evaluation against other related Bunyavirales, such as Hantaan virus and severe fever with thrombocytopenia syndrome virus, is recommended.