Antiviral drug discovery against arthritogenic alphaviruses: Tools and molecular targets

Alphaviruses are (mainly) arthropod-borne viruses that belong to the family of the Togaviridae. Based on the disease they cause, alphaviruses are divided into an arthritogenic and an encephalitic group. Arthritogenic alphaviruses such as the chikungunya virus (CHIKV), the Ross River virus (RRV) and the Mayaro virus (MAYV) have become a serious public health concern in recent years. Epidemics are associated with high morbidity and the infections cause in many patients debilitating joint pain that can persist for months to years. The recent (2013-2014) introduction of CHIKV in the Americas resulted in millions of infected persons. Massive outbreaks of CHIKV and other arthritogenic alphaviruses are likely to occur in the future. Despite the worldwide (re-)emergence of these viruses, there are no antivirals or vaccines available for the treatment or prevention of infections with alphaviruses. It is therefore of utmost importance to develop antiviral strategies against these viruses. We here review the possible molecular targets in the replication cycle of these viruses for the development of antivirals. In addition, we provide an overview of the currently available in vitro systems and mouse infection models that can be used to assess the potential antiviral effect against these viruses.