Small molecule inhibitors of Chikungunya virus: mechanisms of action and antiviral drug resistance.

Small molecule inhibitors of Chikungunya virus: mechanisms of action and antiviral drug resistance. Antimicrob Agents Chemother. 2020 Sep 14;: Authors: Kovacikova K, van Hemert MJ Abstract 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, in silico screens and enzymatic assays with purified viral proteins. We further discuss the current status for 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...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research