Abstract
Naturally occurring plant flavonoids are a promising class of antiviral agents to inhibit African swine fever virus (ASFV), which causes highly fatal disease in pigs and is a major threat to the swine industry. Currently known flavonoids with anti-ASFV activity demonstrate a wide range of antiviral mechanisms, which motivates exploration of new antiviral candidates within this class. The objective of this study was to determine whether other flavonoids may significantly inhibit ASFV infection in vitro. We performed a cell-based library screen of 90 flavonoids. Our screening method allowed us to track the development of virus-induced cytopathic effect by MTT in the presence of tested flavonoids. This screening method was shown to be robust for hit identification, with an average Z-factor of 0.683. We identified nine compounds that inhibit ASFV Ba71V strain in Vero cells. Among them, kaempferol was the most potent and exhibited dose-dependent inhibition, which occurred through a virostatic effect. Time-of-addition studies revealed that kaempferol acts on the entry and post-entry stages of the ASFV replication cycle and impairs viral protein and DNA synthesis. It was further identified that kaempferol induces autophagy in ASFV-infected Vero cells, which is related to its antiviral activity and could be partially abrogated by the addition of an autophagy inhibitor. Kaempferol also exhibited dose-dependent inhibition of a highly virulent ASFV Arm/07 isolate in porcine macrophages. Together, these findings support that kaempferol is a promising anti-ASFV agent and has a distinct antiviral mechanism compared to other anti-ASFV flavonoids.
Highlights
African swine fever (ASF) is a highly contagious hemorrhagic disease that affects wild (Sus scrofa) and domestic (Sus domesticus) pigs of all breeds and is caused by African swine fever virus (ASFV)
Since kaempferol affected early stages of ASFV infection, we further studied the antiviral activity of kaempferol when it was added at the virus entry stage
Since monocytes and macrophages are the main cells for ASFV replication in pigs, we studied the antiviral activity of kaempferol against a highly virulent ASFV isolate (Arm/07) in porcine alveolar macrophages
Summary
African swine fever (ASF) is a highly contagious hemorrhagic disease that affects wild (Sus scrofa) and domestic (Sus domesticus) pigs of all breeds and is caused by African swine fever virus (ASFV). While there has been some progress on the ASFV vaccine development front, widespread vaccination remains a long-term objective and ASFV is a serious and immediate threat to the global pig industry (Zakaryan and Revilla, 2016; Sánchez et al, 2019; Bosch-Camós et al, 2020; Wu et al, 2020). These challenges further underscore the need to develop antiviral drugs for the treatment and prevention of ASFV infection (Arabyan et al, 2019)
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