Inhibition of multiplication of the prototypic arenavirus LCMV by valproic acid

• VPA treatment inhibits LCMV multiplication in cultured cells and Z-mediated budding.
• Viral RNA and protein synthesis are not significantly inhibited by VPA treatment.
• VPA reduces infectious progeny in a higher extent (>2 log) than physical particles.
• Valproic acid is a candidate antiviral drug to combat arenavirus infections.

Valproic acid (VPA), a short chain fatty acid commonly used for treatment of neurological disorders, has been shown to inhibit production of infectious progeny of different enveloped viruses including the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). In this study we have investigated the mechanisms by which VPA inhibits LCMV multiplication in cultured cells. VPA reduced production of infectious LCMV progeny and virus propagation without exerting a major blockage on either viral RNA or protein synthesis, but rather affecting the cell release and specific infectivity of LCMV progeny from infected cells. Our results would support the repurposing of VPA as a candidate antiviral drug to combat arenavirus infections.