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Updated: Jun 23, 2025
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Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
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A pan-respiratory antiviral chemotype targeting a transient host multi-protein complex
Maya Michon1, Andreas Müller-Schiffmann2, Anuradha F Lingappa1
1Prosetta Biosciences, San Francisco, CA, USA.
Open Biology
|June 18, 2024
Summary
A novel antiviral compound targets a specific host protein complex, offering a new strategy against respiratory viruses. This approach shows efficacy in cell cultures and animal models, potentially leading to new treatments.
Area of Science:
- Virology
- Drug Discovery
- Molecular Biology
Background:
- Respiratory viral infections pose a significant global health burden.
- Current antiviral therapies have limitations in spectrum and resistance.
- Targeting host-virus interactions offers a promising therapeutic avenue.
Purpose of the Study:
- To identify novel small molecule antivirals targeting host-virus interactions.
- To validate the efficacy of a new antiviral chemotype against respiratory viruses.
- To elucidate the mechanism of action and host-target engagement.
Main Methods:
- Cell-free protein synthesis and assembly-based phenotypic screening.
- In vitro antiviral activity testing against multiple respiratory virus families.
- In vivo efficacy studies in animal models.
- Biochemical assays to identify target proteins and binding interactions.
Main Results:
- A novel antiviral chemotype was identified, with PAV-431 showing broad-spectrum activity against human respiratory viruses in cell culture.
- PAV-431 demonstrated efficacy in animal models for coronavirus and paramyxovirus infections.
- PAV-431 targets a specific subset of the 14-3-3 protein within a dynamic host-virus-interacting complex.
- An advanced analog, PAV-104, selectively targets the virally modified complex, reducing host toxicity.
Conclusions:
- A new therapeutic strategy targeting the host-virus interface has been developed.
- The identified compounds modulate viral capsid assembly and host innate immunity pathways.
- This approach offers a promising new paradigm for treating respiratory viral diseases with reduced host toxicity.
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