ASFV transcription reporter screening system identifies ailanthone as a broad antiviral compound

African swine fever (ASF) is an acute, highly contagious and deadly viral disease in swine that jeopardizes the worldwide pig industry. Unfortunately, there are no authoritative vaccine and antiviral drug available for ASF control. African swine fever virus (ASFV) is the etiological agent of ASF. Among the ASFV proteins, p72 is the most abundant component in the virions and thus a potential target for anti-ASFV drug design. Here, we con-structed a luciferase reporter system driven by the promoter of p72, which is transcribed by the co-transfected ASFV RNA polymerase complex. Using this system, we screened over 3200 natural product compounds and obtained three potent candidates against ASFV. We further evaluated the anti-ASFV effects and proved that among the three candidates, ailanthone (AIL) inhibits the replication of ASFV at the nanomolar concentration (IC50 1/4 15 nmol/L). Our in vitro experiments indicated that the antiviral effect of AIL is associated with its inhibition of the HSP90-p23 cochaperone. Finally, we showed the antiviral activity of AIL on Zika virus and hepatitis B virus (HBV), which supports that AIL is a potential broad-spectrum antiviral agent.

Automated summary

African swine fever (ASF) is a highly contagious and deadly viral disease in swine that threatens the global pig industry. This study aimed to identify potential antiviral drugs against African swine fever virus (ASFV), which is responsible for ASF. Through a luciferase reporter system driven by the p72 promoter, three potent candidates were discovered from over 3200 natural product compounds. Ailanthone (AIL) showed inhibitory effects on ASFV replication at a nanomolar concentration (IC50 ~ 15 nmol/L). The antiviral activity of AIL was found to be associated with the inhibition of the HSP90-p23 cochaperone. Additionally, AIL demonstrated antiviral activity against Zika virus and hepatitis B virus (HBV), indicating its potential as a broad-spectrum antiviral agent.