Abstract:
:The mammarenavirus Lassa (LASV) is highly prevalent in West Africa where it infects several hundred thousand individuals annually resulting in a high number of Lassa fever (LF) cases, a febrile disease associated with high morbidity and significant mortality. Mounting evidence indicates that the worldwide-distributed prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. There are not Food and Drug Administration (FDA) licensed vaccines and current anti-mammarenavirus therapy is limited to an off-label use of ribavirin that is only partially effective and can cause significant side effects. Therefore, there is an unmet need for novel antiviral drugs to combat LASV. This task would be facilitated by the implementation of high throughput screens (HTS) to identify inhibitors of the activity of the virus ribonucleoprotein (vRNP) responsible for directing virus RNA genome replication and gene transcription. The use of live LASV for this purpose is jeopardized by the requirement of biosafety level 4 (BSL4) containment. We have developed a virus-free cell platform, where expression levels of reporter genes serve as accurate surrogates of vRNP activity, to develop cell-based assays compatible with HTS to identify inhibitors of LASV and LCMV mammarenavirus vRNP activities.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Cubitt B,Ortiz-Riano E,Cheng BY,Kim YJ,Yeh CD,Chen CZ,Southall NOE,Zheng W,Martinez-Sobrido L,de la Torre JCdoi
10.1016/j.antiviral.2019.104667subject
Has Abstractpub_date
2020-01-01 00:00:00pages
104667eissn
0166-3542issn
1872-9096pii
S0166-3542(19)30517-0journal_volume
173pub_type
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