Myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defense

Abstract

Myricetin, a polyhydroxyflavone compound, is one of the main ingredients of various human foods and therefore also known as dietary flavonoids. Due to the continuous emergence of resistant strains of herpesviruses, novel control measures are required. In the present study, myricetin exhibited potent antiviral activity against pseudorabies virus (PRV), a model organism of herpesvirus. The suppression rate could reach up to 96.4% at a concentration of 500 μM in cells, and the 50% inhibitory concentration (IC 50 ) was 42.69 μM. Moreover, the inhibitory activity was not attenuated by the increased amount of infective dose, and a significant reduction of intracellular PRV virions was observed by indirect immunofluorescence. A mode of action study indicated that myricetin could directly inactivate the virus in vitro, leading to inhibition of viral adsorption, penetration and replication in cells. In addition to direct killing effect, myricetin could also activate host antiviral defense through regulation of apoptosis-related gene expressions (Bcl-2, Bcl-xl, Bax), NF-κB and MAPK signaling pathways and cytokine gene expressions (IL-1α, IL-1β, IL-6, c-Jun, STAT1, c-Fos, and c-Myc). In PRV-infected mouse model, myricetin could enhance the survival rate by 40% at 5 days post infection, and viral loads in kidney, liver, lung, spleen, and brain were significantly decreased. The pathological changes caused by PRV infection were improved by myricetin treatment. The gene expressions of inflammatory factors (MCP-1, G-CSF, IL-1α, IL-1β, and IL-6) and apoptotic factors (Bcl-xl, Bcl-2, and Bax) were regulated by myricetin in PRV-infected mice. The present findings suggest that myricetin can effectively inhibit PRV infection and become a candidate for development of new anti-herpesvirus drugs.

Bioinformatics analysis of photoexcited natural flavonoid glycosides as the inhibitors for oropharyngeal HPV oncoproteins

“…(Chen et al 2019 ). Studies have revealed that Myricetin can impede pseudorabies virus infection by directly deactivating the virus and stimulating the host's antiviral defense (Hu et al 2022 ). Previous studies have indicated that the main mechanisms of action for Myricetin involve direct viral killing and inhibition of viral adsorption or penetration (Li et al 2020 ; Wang et al 2023 ).…”

“…Previous studies have indicated that the main mechanisms of action for Myricetin involve direct viral killing and inhibition of viral adsorption or penetration (Li et al 2020 ; Wang et al 2023 ). This makes it a promising candidate for preventing virus infections or for use in combination with other drugs targeting viral replication stages (Hu et al 2022 ). Additionally, Quercetin, a flavonoid commonly found in fruits and vegetables, is well-known for its antioxidant, antiviral, antimicrobial, and anti-inflammatory properties (Di Petrillo et al 2022 ).…”

Dihydromyricetin Inhibits Pseudorabies Virus Multiplication In Vitro by Regulating NF-κB Signaling Pathway and Apoptosis

“…It has been shown that myricetin, luteolin and kaempferol exhibited an inhibitory effect on herpesvirus infection. Myricetin blocks HSV infection by directly interacting with gD while down-regulating the EGFR/PI3K/Akt signaling pathway [ 37 , 38 ]. To prevent EBV reactivation, luteolin reduces the expressions of the promoters of Zta and Rta [ 39 ].…”

Identification of Na+/K+-ATPase Inhibitor Bufalin as a Novel Pseudorabies Virus Infection Inhibitor In Vitro and In Vivo

“…The in vivo experiment was performed as previously described [44]. In brief, a total of 39 female BALB/c mice (4-6 weeks old) were randomly divided into three groups: the control group, the PRV-infected group, and the PRV-infected with bufalin-treated group.…”