Rev-erb Agonist Inhibits Chikungunya and O'nyong'nyong Virus Replication

Chikungunya virus (CHIKV), an alphavirus spread by Aedes spp. mosquitos, causes severe inflammation and joint pain, progressing to a chronic arthralgic state in a subset of patients. Due to recent global epidemics of CHIKV and the potential for related viruses to cause outbreaks, multiple approaches to combat these pathogens are of interest. We report that SR9009, a synthetic agonist of nuclear receptors Rev-erb α/β, inhibits replication of multiple alphaviruses (CHIKV and O'nyong'nyong virus) mainly by suppressing structural protein synthesis, although viral RNA accumulation is relatively unimpeded. Furthermore, SR9009 reduces the inflammatory response in cultured murine macrophages exposed to alphavirus-infected cells.