Repurposing efavirenz, the HIV antiretroviral drug for Chikungunya virus infection

Abstract

Chikungunya virus (CHIKV) is frequently recurring 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 medical countermeasures are available to curb new outbreaks effectively. The interaction of the cytoplasmic domain of E2 (cdE2) with the conserved hydrophobic pocket of capsid protein (CP) is crucial for virus budding. Here, we identified efavirenz molecular interactions with the CP (KD= 6.22 µM), making it a potential antiviral candidate against CHIKV as it is expected to disrupt the cdE2-CP interaction. Subsequently, anti-CHIKV activity of efavirenz by anin-vitrocell based antiviral assay, immunofluorescence assay (IFA), and quantitative reverse transcription polymerase chain reaction (qRT-PCR) was investigated. These studies demonstrated dose-dependent robust anti- CHIKV activity of efavirenz at low micromolar concentration (EC50= 1.33 µM). To demonstrate broad anti-alphavirus activity of efavirenz, its inhibitory activity against Sindbis virus (SINV) was detected. Interestingly, efavirenz also inhibited the replication of SINV at low micromolar range (EC50= 0.7 µM). Efavirenz is the a non-nucleoside reverse transcriptase inhibitor (NNRTI) used to treat acquired immunodeficiency syndrome (AIDS) and it it has good oral bioavailability, long half-life and affordable low cost. Collectively, the present study emphasize the repurposing of efavirenz as an antiviral treatment against CHIKV infection and to curb CHIKV outbreaks in the initial phase.