Ion-Channel-Targeting Drugs for Chikungunya Virus

TL;DR

This paper explores using drugs that target ion channels to combat the Chikungunya virus, a mosquito-borne disease with no current antiviral treatment.

Contribution

The study identifies potential drugs that block the 6K ion channel of Chikungunya virus using repurposed drug screening.

Findings

Several drugs were found to inhibit the 6K protein of Chikungunya virus.

Some drugs also inhibited the 6K protein of Eastern equine encephalitis virus.

Structural specificity of drug effects was observed and supported by modeling.

Abstract

Alphaviruses are transmitted by Aedes mosquitoes and cause large-scale epidemics worldwide. Chikungunya virus (CHIKV) infection can cause febrile seizures known as chikungunya fever (CHIKF), which ultimately leads to severe joint pain and myalgia. While a vaccine has recently been introduced against CHIKV, at present, no anti-viral drug is available. CHIKV, like other alphaviruses, has a short 6K protein capable of forming an ion channel. Blocking this ion channel with drugs can therefore serve as a potential way to curtail CHIKV infection. To that end, we screened a repurposed drug library using three bacteria-based channel assays to detect blockers against 6K viroporin, yielding several hits. Interestingly, several of the blockers were able to inhibit the 6K protein from the similar Eastern equine encephalitis virus (EEEV), while others were not, pointing to structural specificity which may be explained by modeling studies. In conclusion, our study provides a starting point for developing a new route to potentially inhibit CHIKV.

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