Depletion of GTP pool is not the predominant mechanism by which ribavirin exerts its antiviral effect on Lassa virus

  • Ölschläger S
  • Neyts J
  • Günther S
  • 37


    Mendeley users who have this article in their library.
  • 25


    Citations of this article.


Ribavirin (1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is the standard treatment for Lassa fever, though its mode of action is unknown. One possibility is depletion of the intracellular GTP pool via inhibition of the cellular enzyme inosine monophosphate dehydrogenase (IMPDH). This study compared the anti-arenaviral effect of ribavirin with that of two other IMPDH inhibitors, mycophenolic acid (MPA) and 5-ethynyl-1-β-d-ribofuranosylimidazole-4-carboxamide (EICAR). All three compounds were able to inhibit Lassa virus replication by ≥2 log units in cell culture. Restoring the intracellular GTP pool by exogenous addition of guanosine reversed the inhibitory effects of MPA and EICAR, while ribavirin remained fully active. Analogous experiments performed with Zaire Ebola virus showed that IMPDH inhibitors are also active against this virus, although to a lesser extent than against Lassa virus. In conclusion, the experiments with MPA and EICAR indicate that replication of Lassa and Ebola virus is sensitive to depletion of the GTP pool mediated via inhibition of IMPDH. However, this is not the predominant mechanism by which ribavirin exerts its in-vitro antiviral effect on Lassa virus. © 2011 Elsevier B.V.

Author-supplied keywords

  • Arenavirus
  • Ebola virus
  • Inosine monophosphate dehydrogenase
  • Lassa virus
  • Mopeia virus
  • Ribavirin

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Stephan Ölschläger

  • Johan Neyts

  • Stephan Günther

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free