2. Academic Validation
  3. Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens

Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens

  • Antiviral Res. 2018 Jan;149:34-40. doi: 10.1016/j.antiviral.2017.11.004.
Xiao Tong 1,  Jeanon Smith 2,  Natalya Bukreyeva 2,  Takaaki Koma 2,  John T Manning 2,  Raj Kalkeri 3,  Ann D Kwong 4,  Slobodan Paessler 5
Affiliations

Affiliations

  • 1 Trek Therapeutics, PBC, 125 Cambridge Park Drive, Suite 301, Cambridge, MA 02140, USA. Electronic address: xiao.tong@trektx.com.
  • 2 Department of Pathology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
  • 3 Southern Research, 431 Aviation Way, Frederick, MD 21701, USA.
  • 4 Trek Therapeutics, PBC, 125 Cambridge Park Drive, Suite 301, Cambridge, MA 02140, USA.
  • 5 Department of Pathology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA. Electronic address: slpaessl@utmb.edu.
PMID: 29126899 DOI: 10.1016/j.antiviral.2017.11.004
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.

Keywords

Antiviral; Ebola; IMPDH; Merimepodib; VX-497; Zika.

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