Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 64, Issue 12, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01788-20
Keywords
direct-acting antivirals; host-directed antivirals; drug resistance; viral target; high-throughput screening; enzymatic assays; in silico screening; in vivo validation; chikungunya virus
Categories
Funding
- Marie Sklodowska-Curie ETN European Training Network ANTIVIRALS (EU) [642434]
- Marie Curie Actions (MSCA) [642434] Funding Source: Marie Curie Actions (MSCA)
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Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has spread to more than 60 countries worldwide. CHIKV infection leads to a febrile illness known as chikungunya fever (CHIKF), which is characterized by long-lasting and debilitating joint and muscle pain. CHIKV can cause large-scale epidemics with high attack rates, which substantiates the need for development of effective therapeutics suitable for outbreak containment. In this review, we highlight the different strategies used for developing CHIKV small-molecule inhibitors, ranging from high-throughput cell-based screening to in silico screens and enzymatic assays with purified viral proteins. We further discuss the current status of the most promising molecules, including in vitro and in vivo findings. In particular, we focus on describing host and/or viral targets, mode of action, and mechanisms of antiviral drug resistance and associated mutations. Knowledge of the key molecular determinants of drug-resistance will aid selection of the most promising antiviral agent(s) for clinical use. For these reasons, we also summarize the available information about drug resistant phenotypes in Aedes mosquito vectors. From this review, it is evident that more of the active molecules need to be evaluated in preclinical and clinical models to address the current lack of antiviral treatment for CHIKF.
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