Introduction: Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV) are mosquito-borne New World alphaviruses that cause encephalitis in equids and humans. These viruses can cause severe disease and death, as well as long-term severe neurological symptoms in survivors. Despite the pathogenesis and weaponization of these viruses, there are no approved therapeutics for treating infection.
Areas covered: In this review, we describe the molecular pathogenesis of these viruses, discuss host-pathogen interactions needed for viral replication, and highlight new avenues for drug development with a focus on host-targeted approaches.
Expert opinion: Current approaches have yielded some promising therapeutics, but additional emphasis should be placed on advanced development of existing small molecules and pursuit of pan-encephalitic alphavirus drugs. More research should be conducted on EEEV and WEEV, given their high lethality rates.
Keywords: Alphavirus; encephalitis; equine; host-pathogen interaction; pathogenesis; therapeutics.