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Updated: Feb 19, 2026
High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
Published on: October 30, 2021
Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens
Xiao Tong1, Jeanon Smith2, Natalya Bukreyeva2
1Trek Therapeutics, PBC, 125 Cambridge Park Drive, Suite 301, Cambridge, MA 02140, USA.
Abstract:
Zika virus (ZIKV), a member of the Flaviviridae family, has recently been linked to abnormal pregnancies, fetal death, microcephaly, and Guillain-Barré syndrome in humans. Merimepodib (MMPD, VX-497), a potent inhibitor of inosine-5'-monophosphate dehydrogenase (IMPDH), has shown antiviral activity against HCV and a variety of DNA and RNA viruses in vitro. In this report, we expand the antiviral spectrum of MMPD, and demonstrate that MMPD inhibits ZIKV RNA replication with an EC50 of 0.6 μM. Furthermore, MMPD reduces the virus production of ZIKV as well as several other important emerging viral pathogens such as Ebola, Lassa, Chikungunya, and Junin viruses. The inhibition can be reversed by addition of exogenous guanosine to culture media, consistent with the mechanism of action of MMPD as an IMPDH inhibitor. We also provide evidence that MMPD can be used in combination with other antivirals such as ribavirin and T-705 (favipiravir) to enhance suppression of virus production.
Insights
Merimepodib (MMPD) effectively inhibits Zika virus (ZIKV) RNA replication and reduces viral production. This IMPDH inhibitor also shows promise against other emerging viruses and can be combined with antivirals like ribavirin.
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- Zika virus (ZIKV) is a significant public health concern, linked to severe congenital abnormalities and neurological disorders.
- Emerging viral pathogens pose a growing global threat, necessitating novel therapeutic strategies.
- Merimepodib (MMPD, VX-497) is a known inhibitor of inosine-5'-monophosphate dehydrogenase (IMPDH) with demonstrated antiviral activity against other viruses.
Purpose of the Study:
- To investigate the antiviral efficacy of Merimepodib (MMPD) against Zika virus (ZIKV).
- To determine the broader antiviral spectrum of MMPD against other emerging viral pathogens.
- To explore the potential of MMPD in combination therapy for viral infections.
Main Methods:
- In vitro assessment of MMPD's effect on ZIKV RNA replication and virus production.
- Evaluation of MMPD's antiviral activity against Ebola, Lassa, Chikungunya, and Junin viruses.
- Guiding the mechanism of action by testing guanosine rescue experiments.
Main Results:
- MMPD demonstrated potent inhibition of ZIKV RNA replication with an EC50 of 0.6 μM.
- MMPD significantly reduced the production of ZIKV and other tested emerging viruses.
- The antiviral effect of MMPD was reversed by exogenous guanosine, confirming its IMPDH inhibition mechanism.
Conclusions:
- Merimepodib (MMPD) is a potent inhibitor of Zika virus (ZIKV) replication and production.
- MMPD exhibits broad-spectrum antiviral activity against critical emerging viral pathogens.
- Combination therapy with MMPD and other antivirals like ribavirin or favipiravir may enhance viral suppression.
