Myricetin exerts its antiviral activity against infectious bronchitis virus by inhibiting the deubiquitinating activity of papain-like protease

Abstract

Infectious bronchitis virus ( IBV ) is a causative agent that causes severe economic losses in the poultry industry worldwide. Papain-like protease ( PLpro ) is a nonstructural protein encoded by IBV. It has deubiquitinating enzyme activity, which can remove the ubiqutin modification from the protein in nuclear factor kappa-B ( NF-κB ) and interferon regulatory factor 7 ( IRF7 ) signaling pathway, so as to negatively regulate the host's innate immune response to promote viral replication. In this study, PLpro was selected as the target to screen antiviral agents against IBV. Through protein prokaryotic expression technology, we successfully expressed the active IBV PLpro. Among the 16 natural products, myricetin showed the strongest inhibitory effect on IBV PLpro. Next, we tested the antiviral activity of myricetin against IBV and verified whether it can exert antiviral activity by inhibiting the deubiquitinating activity of PLpro. The results showed that myricetin can significantly inhibit IBV replication in primary chicken embryo kidney ( CEK ) cells and it can significantly upregulate the transcription levels in the NF-κB and IRF7 signaling pathways. Moreover, we verified that myricetin can increase the ubiquitin modification level on tumor necrosis factor receptor-associated factor 3 and 6 ( TRAF3 and TRAF6 ) reduced by IBV PLpro. In conclusion, these results indicated that myricetin exerts antiviral activity against IBV by inhibiting the deubiquitinating activity of PLpro, which can provide new perspective for the prevention and treatment of IBV.

Flavonoid Components, Distribution, and Biological Activities in Taxus: A review

“…Compound 20 showed higher inhibitory effect than compound 18 [ 41 ] . Myricetin 21 depicted an apparent restrained effect on infectious bronchitis virus (IBV)at 100 μmol/mL, attenuating the IBV activity closely 50% at 10 μmol/mL by regulating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and interferon regulatory factor 7 (IRF7) pathways [ 44 ]. Different influenza virus evaluations were performed using Quercetin-7-O-glucoside 25 , and the result showed there was a strong inhibitory effect on virus strains with IC 50 of 3.1 to 8.19 µg/mL, accompanied with the decrease of influenza-induced reactive oxygen species and autophagy [ 47 ].…”

Myricetin alleviated hydrogen peroxide-induced cellular senescence of nucleus pulposus cell through regulating SERPINE1

“…MYR shows abundant resource advantages and huge potential utilization value. Multiple effects of MYR have been reported to depend on the therapeutic dose [ 22 ]. Cell viability assay indicated that the higher dose of MYR (40 and 80 μM) significantly inhibited cell growth, while the lower dose groups (10 and 20 μM) showed no cytotoxicity on NPCs.…”

Radix Isatidis polysaccharide (RIP) resists the infection of QX-type infectious bronchitis virus via the MDA5/TLR3/IRF7 signaling pathway

“…Chlorogenic acid affects IBV replication by upregulating MDA5, MAVS, TLR7, MyD88, IRF7, IFN-α, and IFN-β in the trachea and lung ( Abaidullah et al., 2021 ). Myricetin exerts antiviral effects on IBV by enhancing ubiquitin modifications of TRAF3 and TRAF6, which PLpro inhibits, and upregulating the activation of the IRF7 signaling pathway ( Peng et al., 2022 ). The present study shows that RIP increased the downstream expression of IFN-β via increasing the MDA5, TLR3, STING, MyD88, and IRF7 signaling pathways in the kidney and CEK cells to resist viral infection, similar to the results of previous studies.…”