Australian Drug Repurposing Study Uncovers Potential Inhibitors Against Human Metapneumovirus
Nikhil Prasad Fact checked by:Thailand Medical News Team Jan 05, 2025 1 day, 20 hours, 37 minutes ago
Medical News: Human metapneumovirus (HMPV) is a leading cause of respiratory illness worldwide, particularly in children under five, the elderly, and individuals with weakened immune systems. This virus is responsible for conditions ranging from mild upper respiratory infections to severe pneumonia and bronchiolitis, sometimes requiring hospitalization. Despite its prevalence and impact, there are no vaccines or specific antiviral treatments currently available to combat HMPV infections.
Australian Drug Repurposing Study Uncovers Potential Inhibitors Against Human Metapneumovirus
Exploring Drug Repurposing for Rapid Solutions
Researchers at Griffith University's Institute for Glycomics in Queensland, Australia, have pioneered a study exploring drug repurposing as a potential strategy to combat HMPV. Drug repurposing offers a quicker and cost-effective alternative to traditional drug discovery by identifying new uses for existing drugs with established safety profiles.
This
Medical News report delves into the innovative approach used by the research team to screen a vast library of over 2400 approved drugs for their effectiveness against HMPV. The study identified promising candidates with significant antiviral properties, offering hope for faster therapeutic development.
A Breakthrough Screening Process
The researchers developed a medium-throughput screening (MTS) assay to efficiently test the antiviral activity of drugs against HMPV in laboratory conditions. This assay evaluated drug effectiveness by analyzing their ability to inhibit HMPV infection in cultured cells. The initial screening process identified 61 drugs that inhibited HMPV growth by more than 50% at a concentration of 50 micromolar. After refining the list based on dose-response analyses, 11 drugs showed potent, dose-dependent inhibition of HMPV.
The Key Findings
Out of the identified drugs, five demonstrated exceptional potential and low cytotoxicity, meaning they were safe for cells while effectively combating the virus:
-Entry Inhibitors: Evans Blue and aurintricarboxylic acid (ATA) were found to prevent the virus from binding to and entering host cells. These inhibitors work by interacting with the viral surface proteins essential for attachment, making them a critical defense mechanism in the early stages of infection.
-Post-Entry Inhibitors: Mycophenolic acid (MPA), its prodrug mycophenolate mofetil (MPM), and 2,3,4-trihydroxybenzaldehyde emerged as effective compounds in blocking the replication of HMPV once it had entered cells. MPA and MPM were particularly notable for their ability to deplete guanosine levels in cells, disrupting the viral replication process.
Practical Implications and Next Steps
The study highlighted MPA and MPM as especially promising candidates for drug repurposing, as their effective concentrations against HMPV are below the
dosages already approved for human use. This opens the door for their potential application in clinical settings to treat HMPV infections. However, the researchers emphasize the need for further investigations, including testing these drugs in human-derived cell models and clinical trials, to confirm their efficacy and safety for widespread use.
A Critical Look at the Research
While the findings are groundbreaking, certain limitations must be addressed. The study used monkey kidney cells (LLC-MK2), which, although effective for laboratory tests, do not perfectly mimic human cell behavior. Moreover, the efficacy of the identified drugs against other HMPV strains remains to be tested.
Conclusion
The discovery of five effective antiviral drug candidates against HMPV marks a significant leap forward in respiratory virus research. These findings not only provide a foundation for developing targeted therapies but also underscore the value of drug repurposing in addressing pressing global health challenges.
The study findings were published in the peer-reviewed journal: Antimicrobial Agents and Chemotherapy.
https://journals.asm.org/doi/10.1128/aac.01008-22
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