Antiviral drug discovery against arthritogenic alphaviruses: Tools and molecular targets

Abstract

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.

Co-Immunization With CHIKV VLP and DNA Vaccines Induces a Promising Humoral Response in Mice

“…This may be related to the nasal inoculation of CHIKV Ross. CHIKV Ross exhibited a certain neurotoxicity (39). Previous studies have shown that infection with CHIKV Ross can damage brain tissue in mice (40).…”

Life-long passion for antiviral research and drug development: 80th birthday of Prof. Dr. Erik De Clercq

“…With the support of our esteemed professor, we presented a multi-country survey of COVID-19 to characterize mortality-associated factors in elderly males with comorbidities [111] . In addition to remdesivir and dexamethasone, many strategies are still under development to treat COVID-19 [113] , [114] , [115] , [116] , [117] , [118] , [119] , [120] , [121] , [122] , [123] , [124] , [125] , [126] , [127] .…”

Antiviral Strategies against Arthritogenic Alphaviruses

“…Only few of the reported molecules have been tested in alphavirus infection models so far. Infection models in small animals are available for several alphaviruses [ 1 ], but the existing models have limitations since they do not recapitulate all the key aspects of alphavirus disease in humans.…”

“…Alphaviruses are a group of human and animal viruses that belong to the family Togaviridae. Alphaviruses are mainly transmitted by the bite of hematophagous arthropods (e.g., ticks and mosquitoes) [ 1 ]. Classically, alphaviruses are divided into the New World and Old World alphaviruses based on their historical geographical abundance.…”