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

Tan,Kai  Sen; Ng,Wai  Chii; Seet,Ju  Ee; Olfat,Farzad; Engelward,Bevin  P.; Chow,Vincent  T.K.

doi:10.3892/mmr.2013.1750

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

Authors:
- Kai Sen Tan
- Wai Chii Ng
- Ju Ee Seet
- Farzad Olfat
- Bevin P. Engelward
- Vincent T.K. Chow
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Affiliations: Host And Pathogen Interactivity Laboratory, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Republic of Singapore, Department of Pathology, National University Hospital, Singapore 119074, Republic of Singapore, Infectious Diseases Interdisciplinary Research Group, Singapore‑Massachusetts Institute of Technology Alliance for Research and Technology, Singapore 138602, Republic of Singapore
Published online on: October 23, 2013 https://doi.org/10.3892/mmr.2013.1750
Pages: 51-56

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Abstract

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.

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