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Probenecid Treatment Inhibits Replication of the Edmonston Measles Virus Strain in Vero Cells
Jackelyn Murray1, David E Martin2, Ralph A Tripp1
1Department of Infectious Diseases, University of Georgia, Athens, GA 30605, USA.
Abstract:
There are no FDA-approved antiviral treatments for measles virus (MeV). Management is mainly supportive care. MeV treatments may include vitamin A, ribavirin, the MeV vaccine, or human immunoglobulin for pregnant patients exposed to MeV but lacking immunity. The Edmonston strain of MeV serves as the basis for the MeV vaccine and remains a component of the measles-mumps-rubella (MMR) vaccine. We previously showed that probenecid can be used therapeutically to prevent the replication of several key respiratory viruses. This study indicates that pre-treatment with probenecid (prophylaxis) can inhibit the replication of the Edmonston MeV strain in VeroE6 cells (1.12 μM) and Vero-SLAM cells (1.03 μM), while treatment (1 h post-infection, hpi) inhibits replication in VeroE6 cells (1.32 μM) and Vero-SLAM cells (8.66 μM). These results suggest that probenecid is an effective, host-directed antiviral drug against MeV replication in vitro.
Insights
Probenecid effectively inhibits measles virus (MeV) replication in cell cultures. This host-directed antiviral shows promise as a potential therapeutic agent against measles, addressing a gap in current treatment options.
Area of Science:
- Virology
- Pharmacology
- Infectious Diseases
Background:
- Measles virus (MeV) lacks FDA-approved antiviral treatments, necessitating supportive care.
- Current MeV management includes vitamin A, ribavirin, vaccination, and immunoglobulin for specific populations.
- The Edmonston strain of MeV is foundational to the measles vaccine (MMR).
Purpose of the Study:
- To investigate the antiviral potential of probenecid against the Edmonston strain of measles virus.
- To evaluate probenecid's efficacy in inhibiting MeV replication in vitro.
Main Methods:
- Probenecid was tested for its ability to inhibit MeV replication in VeroE6 and Vero-SLAM cell lines.
- Experiments involved both prophylactic (pre-treatment) and therapeutic (post-infection) administration of probenecid.
Main Results:
- Probenecid prophylaxis inhibited Edmonston MeV strain replication in VeroE6 cells (1.12 μM) and Vero-SLAM cells (1.03 μM).
- Therapeutic treatment (1 hour post-infection) inhibited replication in VeroE6 cells (1.32 μM) and Vero-SLAM cells (8.66 μM).
Conclusions:
- Probenecid demonstrates significant in vitro antiviral activity against measles virus.
- These findings suggest probenecid as a potential host-directed antiviral drug for measles treatment.
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