Repurposing HIV antiretroviral drug efavirenz against chikungunya virus

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. Thus, compounds capable of disrupting this interaction can act as effective antiviral drugs. Here, we identified that efavirenz shows interactions with CP (KD = 6.22 μM), thereby it may disrupt the cdE2-CP interaction, making it a potential candidate for developing an antiviral against CHIKV. Subsequently, anti-CHIKV activity of efavirenz by an in-vitro cell culture-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 used for the treatment of HIV infection, here present study indicate that it can be repurposed against CHIKV infection as it has good oral bioavailability, long half-life and affordable low cost indicate great potential as a drug to treat CHIKV-infected individuals and to curb outbreaks in the initial phase.