Antiviral activity of puerarin as potent inhibitor of influenza virus neuraminidase

• Published in: Phytotherapy research 2021-01, Vol.35 (1), p.324-336
• Main Authors: Wang, Hui‐Xian, Zeng, Mao‐Sen, Ye, Yi, Liu, Jin‐Yuan, Xu, Pei‐Ping
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Antioxidants; Antiviral activity; Antiviral Agents - pharmacology; Binding; Cholesterol; Dogs; Exo-a-sialidase; Female; Immunofluorescence; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype - drug effects; influenza virus; Isoflavones - pharmacology; Madin Darby Canine Kidney Cells; Male; Mice; Mice, Inbred BALB C; Mode of action; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Neuraminidase - antagonists & inhibitors; neuraminidase inhibitor; Neuroprotection; Nuclear transport; Orthomyxoviridae Infections - drug therapy; puerarin; Viral Load - drug effects; Viral Proteins - antagonists & inhibitors; Viruses
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.6803

Puerarin is a major isofiavone compound isolated from the root of Pueraria lobata. It was reported that puerarin had antioxidant, antiinflammatory, antitumor, cholesterol lowering, liver protective, and neuroprotective properties. However, few studies have explored the antiviral effect of puerarin and its target mechanism related to influenza virus. Here, the antiinfluenza activity of puerarin in vitro and in vivo and its mode of action on the potential inhibition of neuraminidase (NA) were investigated. Puerarin displayed an inhibitory effect on A/FM/1/1947(H1N1) (EC50 = 52.06 μM). An indirect immunofluorescence assay indicated that puerarin blocked the nuclear export of viral NP. The inhibition of NA activity confirmed that puerarin can block the release of newly formed virus particles from infected cells. Puerarin (100 and 200 mg/kg/d) exhibited effective antiviral activity in mice, conferring 50% and 70% protection from death against H1N1, reducing virus titers, and effectively alleviating inflammation in the lungs. The molecular docking results showed that puerarin had a strong binding affinity with NA from H1N1. The results of the molecular dynamics simulation revealed that puerarin had higher stable binding at the 150‐loop region of the NA protein. These results demonstrated that puerarin acts as a NA blocker to inhibit influenza A virus both in cellular and animal models. Thus, puerarin has potential utility for the treatment of the influenza virus infection.