Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus

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.

First study on in vitro antiviral and virucidal effects of flavonoids against feline infectious peritonitis virus at the early stage of infection

“…Luteolin could exert its antiviral activity through CoV proteins during viral infection. Amentoflavone, a prototype of isoginkgetin, possesses a broad-spectrum antiviral activity against various viruses [ 24 , 47 , 48 ]. However, our results showed that a high concentration of amentoflavone was required to inhibit FIPV replication.…”

The Genus Alternanthera: Phytochemical and Ethnopharmacological Perspectives

“…Siebold ( Fang et al, 2008 ; Singla et al, 2021 ), Vachellia nilotica (L.) P.J.H.Hurter and Mabb. ( Singh et al, 2008 ), etc, with multiple therapeutic potential, including but not limited to antiproliferative ( Park et al, 2021 ), antiviral ( Arabyan et al, 2021 ), hepatoprotective ( Alshehri et al, 2021 ), antioxidant ( Sharma et al, 2021 ), etc. Similarly, chlorogenic acid had been reported from multiple resources, including Cocos nucifera L. ( Bankar et al, 2011 ), apple fruit ( Hulme, 1953 ), Neolamarckia cadamba (Roxb.)…”

Kaempferol Interferes with Varicella-Zoster Virus Replication in Human Foreskin Fibroblasts

“…Flavonoids such as kaempferol, which is known to have pharmacological properties-including anti-inflammatory and anticancer effects [17,18]  are abundant in plants [19]. Kaempferol also inhibits infection of African swine fever virus, Influenza virus, Japanese encephalitis virus, and Herpes simplex virus [20][21][22][23]. Thus, in this study, we investigated the inhibitory effects of kaempferol on VZV infection and its mechanism of action in vitro.…”

“…Furthermore, kaempferol inhibits Japanese encephalitis virus (JEV) by acting directly on JEV RNA [22] and inhibits the entry and post-entry stages of African swine fever virus. The post-entry stage of the virus life cycle is associated with autophagy induction, and kaempferol cell cycle arrest and impacts autophagic processes [20,29]. VZV infections are suppressed by inhibition of autophagy [30].…”