Investigating the efficacy of pamidronate, a chemical inhibitor of farnesyl pyrophosphate synthase, in the inhibition of influenza virus infection in vitro and in vivo

Mol Med Rep. 2014 Jan;9(1):51-6. doi: 10.3892/mmr.2013.1750. Epub 2013 Oct 23.


Influenza A virus has caused significant pandemics in the past decades, including the H1N1‑2009 pandemic. Viperin is an interferon‑inducible protein that acts as a broad‑spectrum antiviral protein via the inhibition of farnesyl pyrophosphate synthase (FPPS). To mimic this activity of viperin, the present study investigated the effectiveness of a commercially available FPPS inhibitor (pamidronate) as an inhibitor of influenza virus infection in vitro and in vivo. HeLaM cells were treated with pamidronate to determine its effect on the replication of influenza virus A/H1N1/WSN/1933. C57BL/6 mice were also subjected to intratracheal pamidronate treatment regimes prior to and following lethal influenza challenge. Treatment with the FPPS inhibitor in vitro resulted in a considerable reduction in the viral titer of ~1 log and diminished lipid raft formation without cellular toxicity, thus mimicking the antiviral effect of viperin. However, pamidronate lacked efficacy in vivo and was associated with increased pulmonary damage, most likely due to the complexity of drug‑host interactions in the infected mice. Further studies are warranted on pamidronate treatment in other infectious diseases that are more susceptible to FPPS inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Diphosphonates / pharmacology*
  • Diphosphonates / therapeutic use
  • Geranyltranstransferase / antagonists & inhibitors*
  • Geranyltranstransferase / metabolism
  • HeLa Cells
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / enzymology
  • Membrane Microdomains / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88 / metabolism
  • Orthomyxoviridae Infections / drug therapy
  • Orthomyxoviridae Infections / mortality
  • Pamidronate
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / metabolism
  • Virus Replication / drug effects


  • Antiviral Agents
  • Diphosphonates
  • Myeloid Differentiation Factor 88
  • Viral Proteins
  • Geranyltranstransferase
  • Pamidronate