Multiple modes of action of myricetin in influenza A virus infection

Abstract

Influenza A virus remains a major threat to public health worldwide after its first pandemic. Scientists keep searching novel anti-influenza drugs, of which natural products present to be an important source. Myricetin, a natural flavonol compound, which exists in many edible plants, which has a wide range of biological activities, but its anti-influenza A virus activity is ambiguous. This study aims to evaluate the antiinfluenza activity of myricetin and elucidate its underlying mechanism. Our results demonstrated that myricetin could significantly inhibit influenza A virus replication, reduce viral polymerase activity via selective inhibition of viral PB2 subunit, and the production of inflammatory cytokines by inhibiting TLR3 signaling pathway. The binding affinity analysis and the result of molecular docking revealed that myricetin interacted with the PB2 cap-binding pocket of influenza A virus. The above results suggested myricetin could exhibit anti-influenza virus activity with low cytotoxicity as well, and myricetin had low toxicity in BALB/c mice in vivo. Results from this study highlighted myricetin could be considered as a promising anti-influenza virus agent with dual inhibition profile. Furthermore, the compound with similar structure would provide a new option for the development of novel inhibitors against influenza A virus.

TRAF3 Positively Regulates Host Innate Immune Resistance to Influenza A Virus Infection

“…The cultural supernatants containing influenza progeny virus were harvested at 12 or 24 h postinfection (indicated in figure legends) and then applied for plaque formation assay to evaluate the virus titers. The overlay solution of plaque assay was prepared as described by Sang ( Sang et al., 2021 ). Briefly, the solution containing 1 μg/ml TPCK-trypsin (Sigma-Aldrich, St. Louis, MO, USA) and 1% penicillin/streptomycin liquid (Gibco, Grand Island, NY, USA) was prepared by mixing 2× DMEM medium into an equivalent microcrystalline cellulose solution.…”

Identification of cytochrome c oxidase subunit 4 isoform 1 as a positive regulator of influenza virus replication

“…BALB/c mice (female, 6–8 weeks old, 16–18 g) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing HFK Bioscience Co. Ltd., China) and bred in BSL-3 facilities at South China Agriculture University (China). This animal strain is widely used in the study of AIV infection ( Sang et al, 2021 ; Wu et al, 2021 ). The mice were housed under controlled temperature, humidity, and lighting (23°C ± 1°C; 12: 12 h light–dark cycle) conditions and provided with free access to food and sterile water.…”

Nisoldipine Inhibits Influenza A Virus Infection by Interfering with Virus Internalization Process

“…The cells were lysed using an RNA isolation kit (Foregene, Chengdu, China). The mRNA expression level was detected with qRT-PCR as previously reported [22]. The relative expression of the viral gene was determined with LightCycler 480 instrument software [22] using a classical 2 -∆∆CT method, with the cellular GAPDH gene serving as the internal control.…”

“…The mRNA expression level was detected with qRT-PCR as previously reported [22]. The relative expression of the viral gene was determined with LightCycler 480 instrument software [22] using a classical 2 -∆∆CT method, with the cellular GAPDH gene serving as the internal control. The PrimeScript™ RT Reagent Kit (TaKaRa, Beijing, China) and the GoTaq ® qPCR Master Mix (Promega, Madison, WI, USA) were used for the RT and qRT-PCR experiments, respectively.…”