Identification of Small-Molecule Inhibitors for Enterovirus A71 IRES by Structure-Based Virtual Screening

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Discovery

Background:

• Structured RNAs regulate gene expression; their dysregulation is linked to infections and cancer.
• Small molecules targeting RNA structures are promising drug candidates.
• Structure-based virtual screening is underutilized for RNA-targeted drug discovery.

Purpose of the Study:

• To develop and apply a virtual screening scheme targeting the EV-A71 IRES SL II RNA structure.
• To identify and optimize small-molecule inhibitors of viral RNA replication.

Main Methods:

• Developed a virtual screening strategy for the EV-A71 IRES SL II RNA.
• Conducted an "analog-by-catalog" search to optimize hit compounds.
• Validated inhibitor potency using biochemical and functional assays.

Main Results:

• Identified a potent inhibitor, IRE-03-3, targeting EV-A71 IRES SL II.
• Achieved an EC50 of 11.96 μM against viral proliferation with IRE-03-3.
• Demonstrated the effectiveness of structure-based virtual screening for RNA targets.

Conclusions:

• Structure-based virtual screening is a viable approach for discovering RNA-targeted drugs.
• The identified inhibitor IRE-03-3 shows potential for antiviral therapeutic development.
• This work opens new avenues for discovering antiviral agents targeting structured RNAs.