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

Xiao Tong, Jeanon Smith, Natalya Bukreyeva, Takaaki Koma, John Manning, Raj Kalkeri, Ann D. Kwong, Slobodan Paessler

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)34-40
Number of pages7
JournalAntiviral Research
Volume149
DOIs
StatePublished - Jan 1 2018

Fingerprint

IMP Dehydrogenase
Antiviral Agents
Lassa virus
Junin virus
Flaviviridae
Chikungunya virus
Ebolavirus
Viruses
Microcephaly
DNA Viruses
Fetal Death
Guanosine
Ribavirin
RNA Viruses
Virus Replication
Culture Media
RNA
Pregnancy
N-3-(3-(3-methoxy-4-oxazol-5-ylphenyl)ureido)benzylcarbamic acid tetrahydrofuran-3-yl ester
Zika Virus

Keywords

  • Antiviral
  • Ebola
  • IMPDH
  • Merimepodib
  • VX-497
  • Zika

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Cite this

Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens. / Tong, Xiao; Smith, Jeanon; Bukreyeva, Natalya; Koma, Takaaki; Manning, John; Kalkeri, Raj; Kwong, Ann D.; Paessler, Slobodan.

In: Antiviral Research, Vol. 149, 01.01.2018, p. 34-40.

Research output: Contribution to journalArticle

Tong, Xiao ; Smith, Jeanon ; Bukreyeva, Natalya ; Koma, Takaaki ; Manning, John ; Kalkeri, Raj ; Kwong, Ann D. ; Paessler, Slobodan. / Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens. In: Antiviral Research. 2018 ; Vol. 149. pp. 34-40.
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