Tingting Li,Jun Zheng,Tao Huang,Xiao Wang,Jiangnan Li,Feng Jin,Wenjuan Wei,Xin Chen,Chuanxia Liu,Miaofei Bao,Gaihong Zhao,Li Huang,Dongming Zhao,Jianxin Chen,Zhigao Bu,Changjiang Weng

Virology.2024 Feb 14:593:110014.doi: 10.1016/j.virol.2024.110014. Online ahead of print.

Abstract

African swine fever (ASF) caused by African swine fever virus (ASFV) is a highly infectious and lethal swine disease. Currently, there is only one novel approved vaccine and no antiviral drugs for ASFV. In the study, a high-throughput screening of an FDA-approved drug library was performed to identify several drugs against ASFV infection in primary porcine alveolar macrophages. Triapine and cytarabine hydrochloride were identified as ASFV infection inhibitors in a dose-dependent manner. The two drugs executed their antiviral activity during the replication stage of ASFV. Furthermore, molecular docking studies showed that triapine might interact with the active center Fe2+ in the small subunit of ASFV ribonucleotide reductase while cytarabine hydrochloride metabolite might interact with three residues (Arg589, Lys593, and Lys631) of ASFV DNA polymerase to block new DNA chain extension. Taken together, our results suggest that triapine and cytarabine hydrochloride displayed significant antiviral activity against ASFV in vitro.

Keywords: African swine fever virus; Cytarabine hydrochloride; FDA-approved drugs; Inhibitors; Triapine.