Emodin and rhapontigenin inhibit the replication of African swine fever virus by interfering with virus entry

Abstract

Africa swine fever (ASF) is a highly pathogenic contagion caused by African swine fever virus (ASFV), which not only affects the development of domestic pig industry, but also causes huge losses to the world agricultural economy. Vaccine development targeting ASFV remains elusive, which leads to severe difficulties in disease prevention and control. Emodin (EM) and rhapontigenin (RHAG), which are extracted from the dried rhizome of Polygonum knotweed, have various biological properties such as anti-neoplastic and anti-bacterial activities, but no studies have reported that they have anti-ASFV effects. This study discovered that EM and RHAG at different concentrations had a significant dose-dependent inhibitory effect on the ASFV GZ201801 strain in porcine alveolar macrophages (PAMs), and at the specified concentration, EM and RHAG showed continuous inhibition at 24 h, 48 h and 72 h. Not only did they strongly impact virion attachment and internalization, but also inhibit the early stages of ASFV replication. Further research proved that the expression level of Rab 7 protein was reduced by EM and RHAG, and treatments with EM and RHAG induced the accumulation of free cholesterol in endosomes and inhibited endosomal acidification, which prevented the virus from escaping and shelling from late endosomes. This study summarized the application of EM and RHAG in inhibiting ASFV replication in-vitro. Similarly, EM and RHAG targeted Rab 7 in the viral endocytosis pathway, inhibited viral infection, and induced the accumulation of cholesterol in the endosomes and the acidification of the endosomes to inhibit uncoating. A reference could be made to the results of this study when developing antiviral drugs and vaccines.

Keywords: ASFV; Cholesterol; Emodin; Endosomal acidification; Rab 7; Rhapontigenin.