tetano
Editor, Senior Moderator
Microbes Infect
. 2020 Jun 15;S1286-4579(20)30100-3.
doi: 10.1016/j.micinf.2020.05.021. Online ahead of print.
Dihydromyricetin Is a New Inhibitor of Influenza Polymerase PB2 Subunit and Influenza-Induced Inflammation
Yuanxin Tian[SUP] 1 [/SUP], Huiting Sang[SUP] 1 [/SUP], Miaomiao Liu[SUP] 1 [/SUP], Fangzhao Chen[SUP] 1 [/SUP], Yingna Huang[SUP] 1 [/SUP], Lin Li[SUP] 2 [/SUP], Shuwen Liu[SUP] 3 [/SUP], Jie Yang[SUP] 4 [/SUP]
Affiliations
Abstract
Development of new and effective anti-influenza drugs is critical for the treatment of influenza virus infection. The polymerase basic 2 (PB2) subunit as a core subunit of influenza A virus RNA polymerase complex is considered to be an attractive drug target for anti-influenza drug discovery. Dihydromyricetin, as a natural flavonoid, has a wide range of biological activities, but its anti-influenza A virus activity is ambiguous. Here, we found dihydromyricetin could inhibit the replication of a variety of influenza A virus strains. Mechanism studies demonstrated that dihydromyricetin reduced viral polymerase activity via selective inhibition of viral PB2 subunit, and decreased relative amounts of viral mRNA and genomic RNA during influenza A virus infection. The binding affinity and molecular docking analyses revealed that dihydromyricetin interacted with the PB2 cap-binding pocket, functioned as a cap-binding competitor. Interestingly, dihydromyricetin also reduced cellular immune injury by inhibiting TLR3 signaling pathway. Additionally, combination treatment of dihydromyricetin with zanamivir exerted a synergistic anti-influenza effect. Altogether, our experiments reveal the antiviral and anti-inflammatory activities of dihydromyricetin in vitro against influenza virus infection, which provides a new insight into the development of novel anti-influenza drugs.
Keywords: Dihydromyricetin; TLR3; anti-inflammatory; influenza A virus; influenza polymerase basic 2.
. 2020 Jun 15;S1286-4579(20)30100-3.
doi: 10.1016/j.micinf.2020.05.021. Online ahead of print.
Dihydromyricetin Is a New Inhibitor of Influenza Polymerase PB2 Subunit and Influenza-Induced Inflammation
Yuanxin Tian[SUP] 1 [/SUP], Huiting Sang[SUP] 1 [/SUP], Miaomiao Liu[SUP] 1 [/SUP], Fangzhao Chen[SUP] 1 [/SUP], Yingna Huang[SUP] 1 [/SUP], Lin Li[SUP] 2 [/SUP], Shuwen Liu[SUP] 3 [/SUP], Jie Yang[SUP] 4 [/SUP]
Affiliations
- PMID: 32554102
- DOI: 10.1016/j.micinf.2020.05.021
Abstract
Development of new and effective anti-influenza drugs is critical for the treatment of influenza virus infection. The polymerase basic 2 (PB2) subunit as a core subunit of influenza A virus RNA polymerase complex is considered to be an attractive drug target for anti-influenza drug discovery. Dihydromyricetin, as a natural flavonoid, has a wide range of biological activities, but its anti-influenza A virus activity is ambiguous. Here, we found dihydromyricetin could inhibit the replication of a variety of influenza A virus strains. Mechanism studies demonstrated that dihydromyricetin reduced viral polymerase activity via selective inhibition of viral PB2 subunit, and decreased relative amounts of viral mRNA and genomic RNA during influenza A virus infection. The binding affinity and molecular docking analyses revealed that dihydromyricetin interacted with the PB2 cap-binding pocket, functioned as a cap-binding competitor. Interestingly, dihydromyricetin also reduced cellular immune injury by inhibiting TLR3 signaling pathway. Additionally, combination treatment of dihydromyricetin with zanamivir exerted a synergistic anti-influenza effect. Altogether, our experiments reveal the antiviral and anti-inflammatory activities of dihydromyricetin in vitro against influenza virus infection, which provides a new insight into the development of novel anti-influenza drugs.
Keywords: Dihydromyricetin; TLR3; anti-inflammatory; influenza A virus; influenza polymerase basic 2.