Current drug discovery strategies against arenavirus infections

Abstract

Arenaviruses are a large group of emerging viruses including several causative agents of severe hemorrhagic fevers with high mortality in man. Considering the number of people affected and the currently limited therapeutic options, novel efficacious therapeutics against arenaviruses are urgently needed. Over the past decade, significant advances in knowledge about the basic virology of arenaviruses have been accompanied by the development of novel therapeutics targeting different steps of the arenaviral life cycle. High-throughput, small-molecule screens identified potent and broadly active inhibitors of arenavirus entry that were instrumental for the dissection of unique features of arenavirus fusion. Novel inhibitors of arenavirus replication have been successfully tested in animal models and hold promise for application in humans. Late in the arenavirus life cycle, the proteolytic processing of the arenavirus envelope glycoprotein precursor and cellular factors critically involved virion assembly and budding provide further promising ‘druggable’ targets for novel therapeutics to combat human arenavirus infection.

Keywords::

• antiviral drug
• arenavirus
• budding
• cellular factor
• combinatorial therapy
• entry inhibitor
• hemorrhagic fever
• viral replication

Acknowledgements

We thank A Telenti (University of Lausanne, Switzerland) for his generous support.

Financial & competing interests disclosure

This work was supported by the Swiss National Science Foundation grant no. 31003A-135536 (S Kunz), Swiss National Science Foundation grant no. 310030-132844 (S Kunz) and the Prix Leenaards 2009 Pour la Promotion de la Recherche Scientifique (S Kunz). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.