The ReFRAME library as a comprehensive drug repurposing library to identify mammarenavirus inhibitors.

The ReFRAME library as a comprehensive drug repurposing library to identify mammarenavirus inhibitors. Antiviral Res. 2019 Jul 11;:104558 Authors: Kim YJ, Cubitt B, Chen E, Hull MV, Chatterjee AK, Cai Y, Kuhn JH, de la Torre JC Abstract Several mammarenaviruses, chiefly Lassa virus (LASV) in Western Africa and Junín virus (JUNV) in the Argentine Pampas, cause severe disease in humans and pose important public health problems in their endemic regions. Moreover, mounting evidence indicates that the worldwide-distributed mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. The lack of licensed mammarenavirus vaccines and partial efficacy of current anti-mammarenavirus therapy limited to an off-label use of the nucleoside analog ribavirin underscore an unmet need for novel therapeutics to combat human pathogenic mammarenavirus infections. This task can be facilitated by the implementation of "drug repurposing" strategies to reduce the time and resources required to advance identified antiviral drug candidates into the clinic. We screened a drug repurposing library of 11,968 compounds (Repurposing, Focused Rescue and Accelerated Medchem [ReFRAME]) and identified several potent inhibitors of LCMV multiplication that had also strong anti-viral activity against LASV and JUNV. Our findings indicate that enzymes of the rate-limiting steps of pyrimidine and purine biosynthesis, the pr...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research