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Probenecid Inhibits Human Metapneumovirus (HMPV) Replication In Vitro and in BALB/c Mice
Harrison C Bergeron1, Jackelyn Crabtree1, Tamas Nagy2
1Department of Infectious Diseases, University of Georgia, Athens, GA 30605, USA.
Abstract:
Human metapneumovirus (HMPV) is an important cause of acute respiratory tract infection and causes significant morbidity and mortality. There is no specific antiviral drug to treat HMPV or vaccine to prevent HMPV. This study determined if probenecid, a host-targeting antiviral drug, had prophylactic (pre-virus) or therapeutic (post-virus) efficacy to inhibit HMPV replication in LLC-MK2 cells in vitro and in the lungs of BALB/c mice. This study showed that ≥0.5 μM probenecid significantly inhibited HMPV replication in vitro, and 2-200 mg/kg probenecid prophylaxis or treatment reduced HMPV replication in BALB/c mice.
Insights
Probenecid shows promise as an antiviral treatment for human metapneumovirus (HMPV) infection. This study found probenecid inhibited HMPV replication in cell cultures and in mouse models, suggesting its potential as a therapeutic drug.
Area of Science:
- Virology
- Infectious Diseases
- Pharmacology
Background:
- Human metapneumovirus (HMPV) is a significant cause of respiratory illness, leading to considerable morbidity and mortality.
- Currently, no specific antiviral therapies or preventative vaccines exist for HMPV infections.
Purpose of the Study:
- To investigate the potential of probenecid, a host-targeting antiviral, in inhibiting HMPV replication.
- To evaluate both prophylactic and therapeutic efficacy of probenecid against HMPV in vitro and in vivo.
Main Methods:
- In vitro studies using LLC-MK2 cells to assess HMPV replication inhibition by probenecid.
- In vivo studies involving BALB/c mice to evaluate probenecid's prophylactic and therapeutic effects on HMPV lung infection.
Main Results:
- Probenecid demonstrated significant inhibition of HMPV replication in vitro at concentrations of ≥0.5 μM.
- Probenecid administration (2-200 mg/kg) as prophylaxis or treatment effectively reduced HMPV replication in the lungs of BALB/c mice.
Conclusions:
- Probenecid exhibits antiviral activity against HMPV in both cell culture and animal models.
- These findings suggest that probenecid could be a potential therapeutic agent for managing HMPV infections.
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