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Updated: Aug 29, 2025
High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
Drug Repurposing for Therapeutic Discovery against Human Metapneumovirus Infection
Annelies Van Den Bergh1, Patrice Guillon1, Mark von Itzstein1
1Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland, Australia.
Abstract:
Human metapneumovirus (HMPV) is recognized as an important cause of pneumonia in infants, in the elderly, and in immunocompromised individuals worldwide. The absence of an antiviral treatment or vaccine strategy against HMPV infection creates a high burden on the global health care system. Drug repurposing has become increasingly attractive for the treatment of emerging and endemic diseases as it requires less research and development costs than traditional drug discovery. In this study, we developed an in vitro medium-throughput screening assay that allows for the identification of novel anti-HMPV drugs candidates. Out of ~2,400 compounds, we identified 11 candidates with a dose-dependent inhibitory activity against HMPV infection. Additionally, we further described the mode of action of five anti-HMPV candidates with low in vitro cytotoxicity. Two entry inhibitors, Evans Blue and aurintricarboxylic acid, and three post-entry inhibitors, mycophenolic acid, mycophenolate mofetil, and 2,3,4-trihydroxybenzaldehyde, were identified. Among them, the mycophenolic acid series displayed the highest levels of inhibition, due to the blockade of intracellular guanosine synthesis. Importantly, MPA has significant potential for drug repurposing as inhibitory levels are achieved below the approved human oral dose. Our drug-repurposing strategy proved to be useful for the rapid discovery of novel hit candidates to treat HMPV infection and provide promising novel templates for drug design.
Insights
Drug repurposing identified 11 compounds to treat human metapneumovirus (HMPV) infection. Mycophenolic acid showed high inhibition by blocking guanosine synthesis, offering a promising antiviral strategy.
Area of Science:
- Virology
- Drug Discovery
- Immunology
Background:
- Human metapneumovirus (HMPV) causes significant pneumonia globally, particularly in vulnerable populations.
- Lack of effective antiviral treatments or vaccines for HMPV results in a substantial global health burden.
- Drug repurposing offers a cost-effective approach to identify new treatments for emerging and endemic diseases.
Purpose of the Study:
- To develop and implement an in vitro medium-throughput screening assay for identifying novel anti-HMPV drug candidates.
- To screen approximately 2,400 compounds for their ability to inhibit HMPV infection.
- To characterize the mechanism of action and cytotoxicity of identified anti-HMPV compounds.
Main Methods:
- Development of a medium-throughput in vitro screening assay for HMPV inhibition.
- Screening of ~2,400 diverse chemical compounds.
- Characterization of antiviral activity, cytotoxicity, and mechanism of action for hit compounds.
Main Results:
- Identified 11 compounds exhibiting dose-dependent inhibition of HMPV infection.
- Characterized five compounds with low in vitro cytotoxicity: two entry inhibitors (Evans Blue, aurintricarboxylic acid) and three post-entry inhibitors (mycophenolic acid, mycophenolate mofetil, 2,3,4-trihydroxybenzaldehyde).
- Mycophenolic acid (MPA) demonstrated potent inhibition by blocking intracellular guanosine synthesis, with effective concentrations below the approved human oral dose.
Conclusions:
- The drug repurposing strategy successfully identified novel anti-HMPV candidates.
- Mycophenolic acid shows significant potential for treating HMPV infections due to its efficacy and favorable dosing.
- Identified compounds provide promising templates for future antiviral drug design against HMPV.
