Off label antiviral therapeutics for henipaviruses: new light through old windows

Aljofan, Mohamad, Lo, Michael K., Rota, Paul A., Michalski, Wojtek P. and Mungall, Bruce A. (2010) Off label antiviral therapeutics for henipaviruses: new light through old windows. Journal of Antivirals and Antiretrovirals, 2 1: 1-10. doi:10.4172/jaa.1000014

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Author Aljofan, Mohamad
Lo, Michael K.
Rota, Paul A.
Michalski, Wojtek P.
Mungall, Bruce A.
Title Off label antiviral therapeutics for henipaviruses: new light through old windows
Journal name Journal of Antivirals and Antiretrovirals   Check publisher's open access policy
ISSN 1948-5964
Publication date 2010-02
Sub-type Article (original research)
DOI 10.4172/jaa.1000014
Open Access Status DOI
Volume 2
Issue 1
Start page 1
End page 10
Total pages 10
Place of publication Foster City, CA, United States
Publisher Omics Publishing Group
Language eng
Subject 2406 Virology
2725 Infectious Diseases
Formatted abstract
Hendra and Nipah viruses are recently emerged zoonotic paramyxoviruses for which there is no vaccine or protective therapy available. While a number of experimental therapeutics and vaccines have recently been reported, all of these will require lengthy approval processes, limiting their usefulness in the short term. To address the urgent need for henipavirus therapeutics, a number of currently licensed pharmaceuticals have been evaluated for off label efficacy against henipavirus replication in vitro. Initially it was observed that compounds which released intracellular calcium stores induced a potent inhibition of henipaviruses replication, prompting the evaluation of known drugs with a similar effect on calcium mobilisation. Of the eight compounds randomly selected based on existing literature, seven inhibited virus replication in the micromolar range while the remaining compound also inhibited virus replication but only at millimolar concentrations. Pretreatment experiments with various calcium chelators, channel antagonists or endoplasmic reticulum release inhibitors supported a calcium mediated mechanism of action for five of these compounds. The mechanism of antiviral action for the remaining three compounds is currently unknown. Additionally, a number of other modulators of calcium flux, including calcium channel and calmodulin antagonists also exhibited potent antiviral activity in vitro providing a broad range of potential therapeutic options for the treatment of henipavirus infections. Importantly, as many of these compounds are currently licensed drugs, regulatory approval should be a much more streamlined process, with the caveat that appropriate in vivo efficacy can be demonstrated in animal models.
Keyword Nipah virus
Hendra virus
Henipaviruses
Antiviral
Calcium
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Veterinary Science Publications
 
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