Small molecules targeting viral RNA.

Area of Science:

• Virology and RNA Therapeutics
• Drug Discovery and Medicinal Chemistry

Background:

• Highly conserved noncoding RNA (ncRNA) in viral genomes and transcripts represent promising, yet underexplored, targets for antiviral drug development.
• Small molecules binding to ncRNA can disrupt essential viral replication processes by altering RNA structure and interactions.

Purpose of the Study:

• To review the potential of targeting viral ncRNA with small molecule inhibitors for anti-infective therapy.
• To highlight successful strategies and emerging insights for identifying drug-like small molecules that inhibit viral replication by targeting ncRNA.

Main Methods:

• Review of existing literature on small molecule inhibitors targeting viral ncRNA.
• Analysis of successful lead discovery efforts for RNA targets in various viruses.
• Discussion of challenges, such as target selectivity, and properties of amenable RNA targets.

Main Results:

• Proof-of-concept for targeting functional viral RNA with small molecule inhibitors has been established for multiple RNA viruses.
• Drug-like small molecules inhibiting viral replication have been identified for human immunodeficiency virus (HIV), hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and influenza A virus.
• Emerging understanding of RNA target properties suitable for small molecule inhibition.

Conclusions:

• Targeting viral ncRNA is a viable strategy for developing novel antiviral therapies.
• Insights from successful targeting of ncRNA in HIV, HCV, SARS-CoV, and influenza can guide the development of therapeutics for other viral pathogens.
• Promising future applications include targeting insect-borne flaviviruses (Dengue, Zika, West Nile) and filoviruses (Ebola, Marburg).