A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.

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 Res

journal_title

Antiviral research

authors

Cubitt B,Ortiz-Riano E,Cheng BY,Kim YJ,Yeh CD,Chen CZ,Southall NOE,Zheng W,Martinez-Sobrido L,de la Torre JC

doi

10.1016/j.antiviral.2019.104667

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

104667

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(19)30517-0

journal_volume

173

pub_type

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