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High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
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Self-assembling short immunostimulatory duplex RNAs with broad-spectrum antiviral activity
Longlong Si1, Haiqing Bai1, Crystal Yuri Oh1
1Wyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Molecular Therapy. Nucleic Acids
|August 29, 2022
Summary
Researchers developed novel self-assembling RNA molecules that stimulate the immune system to fight viruses. These short duplex RNAs show broad-spectrum antiviral activity against respiratory viruses, offering potential for new therapeutics.
Area of Science:
- Molecular Biology
- Immunology
- Virology
Background:
- The COVID-19 pandemic underscores the urgent need for effective, broad-spectrum antiviral treatments.
- Current antiviral strategies often target specific viruses, limiting their utility against emerging threats.
Purpose of the Study:
- To describe a new class of self-assembling immunostimulatory short duplex RNAs.
- To investigate their mechanism of action and potential as broad-spectrum antiviral therapeutics.
Main Methods:
- Design and synthesis of novel short duplex RNAs with specific sequence motifs.
- Assessment of interferon (IFN-I and IFN-III) induction in cell lines and human lung chips.
- Evaluation of antiviral activity against SARS-CoV-2, MERS-CoV, HCoV-NL63, and influenza A virus in vitro and in vivo mouse models.
Main Results:
- The novel RNAs self-assemble into dimers and potently induce IFN-I and IFN-III production.
- Their activity is independent of TLR 7/8 but requires the RIG-I/IRF3 pathway, resulting in a lower proinflammatory signature.
- Demonstrated broad-spectrum inhibition of multiple respiratory viruses, including SARS-CoV-2, in various experimental models.
Conclusions:
- These self-assembling short duplex RNAs represent a new class of immunostimulatory agents with significant broad-spectrum antiviral potential.
- Their ease of manufacturing and potent antiviral activity suggest they could be developed into novel therapeutics for respiratory viral infections.
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