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Development of a Universal Type A Influenza Viral RdRp-Induced Reporter System with Potential for Antiviral Drug
Yuehong Chen1, Wenguang Yang1, Liangning Liao2
1State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, Beijing 100071, China.
ACS Infectious Diseases
|May 27, 2025
Summary
A new universal cell-based reporter system enables rapid screening of antiviral drugs targeting influenza virus RNA-dependent RNA polymerase (RdRp). This assay accelerates the development of next-generation influenza antivirals without modifying viruses.
Area of Science:
- Virology
- Antiviral Drug Discovery
- Molecular Biology
Background:
- Influenza virus poses a continuous threat due to emerging strains and drug resistance.
- Existing reporter virus assays for antiviral screening are time-consuming and strain-specific.
- Novel antiviral therapies are urgently needed to combat influenza.
Purpose of the Study:
- To develop a universal reporter system for assessing antiviral drug efficacy against influenza A virus (IAV).
- To establish a rapid and sensitive assay for screening drugs targeting viral RNA-dependent RNA polymerase (RdRp).
Main Methods:
- Developed a Madin-Darby canine kidney (MDCK) cell-based reporter system utilizing Gaussia luciferase (Gluc) expression.
- Gluc expression was driven by a Pol-II promoter and IAV RNA promoters recognized by different influenza polymerase complexes.
- Assessed viral RdRp activity by measuring Gluc luminescence, correlating it with viral RNA replication.
Main Results:
- Confirmed a direct correlation between Gluc activity and influenza virus RNA replication.
- Demonstrated positive correlation between Gluc expression and RdRp inhibitor efficacy against H1N1, H3N2, and H9N2 viruses.
- The assay showed sensitivity and rapidity in evaluating drug effects without virus modification.
Conclusions:
- Established a universal, sensitive, and rapid assay for influenza RdRp drug discovery.
- This system accelerates the development of next-generation antivirals.
- Facilitates rapid testing of novel antiviral compounds against emerging influenza variants.
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