Abstract:
:Viral hemorrhagic fevers (VHFs) cause thousands of fatalities every year, but the treatment options for their management remain very limited. In particular, the development of therapeutic interventions is restricted by the lack of commercial viability of drugs targeting individual VHF agents. This makes approaches like drug repurposing and/or the identification of broad range therapies (i.e. those directed at host responses or common proviral factors) highly attractive. However, the identification of candidates for such antiviral repurposing or of host factors/pathways important for the virus life cycle is reliant on high-throughput screening (HTS). Recently, such screening work has been increasingly facilitated by the availability of reverse genetics-based approaches, including tools such as full-length clone (FLC) systems to generate reporter-expressing viruses or various life cycle modelling (LCM) systems, many of which have been developed and/or greatly improved during the last years. In particular, since LCM systems are capable of modelling specific steps in the life cycle, they are a valuable tool for both targeted screening (i.e. for inhibitors of a specific pathway) and mechanism of action studies. This review seeks to summarize the currently available reverse genetics systems for negative-sense VHF causing viruses (i.e. arenaviruses, bunyaviruses and filoviruses), and to highlight the recent advancements made in applying these systems for HTS to identify either antivirals or new virus-host interactions that might hold promise for the development of future treatments for the infections caused by these deadly but neglected virus groups.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Wendt L,Bostedt L,Hoenen T,Groseth Adoi
10.1016/j.antiviral.2019.104569subject
Has Abstractpub_date
2019-10-01 00:00:00pages
104569eissn
0166-3542issn
1872-9096pii
S0166-3542(19)30287-6journal_volume
170pub_type
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