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Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice

  • Eun-Hye Hong (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Jae-Hyoung Song (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Seong-Ryeol Kim (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Jaewon Cho (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Birang Jeong (Laboratory of Natural Products Chemistry, College of Pharmacy, Kangwon National University) ;
  • Heejung Yang (Laboratory of Natural Products Chemistry, College of Pharmacy, Kangwon National University) ;
  • Jae-Hyeon Jeong (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Jae-Hee Ahn (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Hyunjin Jeong (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Seong-Eun Kim (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Sun-Young Chang (Laboratory of Microbiology and Immunology, College of Pharmacy, Ajou University) ;
  • Hyun-Jeong Ko (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University)
  • Received : 2020.04.06
  • Accepted : 2020.07.09
  • Published : 2020.08.31
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Abstract

Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-κB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and Ministry of Education (grant numbers: NRF-2020R1A2B5B02001552, NRF-2019R1I1A1A01060238, and NRF-2017R1A6A3A11031757). This study has been worked with the support of a research grant of Kangwon National University in 2017.

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