Repurposing efavirenz, the HIV antiretroviral drug for Chikungunya virus infection.

Chikungunya virus (CHIKV) has frequently recurred in recent decades, causing outbreaks worldwide in tropical and subtropical regions. The re-emergence of CHIKV poses a substantial risk to human health as no efficacious drugs are currently available to curb new outbreaks. Here, the anti-CHIKV activity of efavirenz was investigated by in vitro cell culture-based antiviral assay, immunofluorescence assay (IFA), and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used for treatment of acquired immunodeficiency syndrome (AIDS), and it has good oral bioavailability, long half-life and affordable low cost. This study demonstrated dose-dependent robust anti-CHIKV activity of efavirenz at low micromolar concentration (EC50 = 1.33 {micro}M). To determine potential broad anti-alphavirus activity of efavirenz, its inhibitory activity against Sindbis virus (SINV) was detected. Interestingly, efavirenz also inhibited the replication of SINV at a low micromolar range (EC50 = 0.7 {micro}M). Time of addition assay, direct transfection of virus replicon RNA and minus-sense specific RT-PCR elucidated that efavirenz hinders the viral replication at an early stage after the virus entry by inhibiting the viral RNA synthesis. Efavirenz showed a binding affinity with purified CHIKV capsid protein (CHIKV CP) and it is known that CHIKV CP plays a novel role in the early phase of viral protein synthesis, suggesting CP might be one of the potential protein targets in addition to viral or host proteins involved in viral genome replication. The present study underscores the repurposing of efavirenz for antiviral therapy against CHIKV to curb future viral outbreaks. HighlightsIdentification of in vitro anti-CHIKV activity of efavirenz. Efavirenz disrupts the early phase of virus replication by interfering in the CHIKV minus-sense RNA synthesis. Efavirenz and tomatidine also inhibit SINV replication indicating potential broad spectrum anti-alphavirus activity. Efavirenz holds potential as therapeutic treatment for clinical infections of Chikungunya.