title: Antiviral activity of chlorogenic acid against influenza A (H1N1/H3N2) virus and its inhibition of neuraminidase.
abstract: Lonicera japonica Thunb, rich in chlorogenic acid (CHA), is used for viral upper respiratory tract infection treatment caused by influenza virus, parainfluenza virus, and respiratory syncytial virus, ect in China. It was reported that CHA reduced serum hepatitis B virus level and death rate of influenza virus-infected mice. However, the underlying mechanisms of CHA against the influenza A virus have not been fully elucidated. Here, the antiviral effects and potential mechanisms of CHA against influenza A virus were investigated. CHA revealed inhibitory against A/PuertoRico/8/1934(H1N1) (EC50= 44.87 μM), A/Beijing/32/92(H3N2) (EC50= 62.33 μM), and oseltamivir-resistant strains. Time-course analysis showed CHA inhibited influenza virus during the late stage of infectious cycle. Indirect immunofluorescence assay indicated CHA down-regulated the NP protein expression. The inhibition of neuraminidase activity confirmed CHA blocked release of newly formed virus particles from infected cells. Intravenous injection of 100 mg/kg/d CHA possessed effective antiviral activity in mice, conferring 60% and 50% protection from death against H1N1 and H3N2, reducing virus titres and alleviating inflammation in the lungs effectively. These results demonstrate that CHA acts as a neuraminidase blocker to inhibit influenza A virus both in cellular and animal models. Thus, CHA has potential utility in the treatment of the influenza virus infection.
authors.affiliation: State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, Jiangsu, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ding
authors.affiliation: State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, Jiangsu, China.
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Cao
authors.affiliation: State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, Jiangsu, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cao
authors.affiliation: State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, Jiangsu, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ding
authors.affiliation: State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, Jiangsu, China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D002726:Chlorogenic Acid / Q000008:administration & dosage*; D004285:Dogs; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000517:prevention & control; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000037:antagonists & inhibitors*
chemical_list: D000998:Antiviral Agents; D002726:Chlorogenic Acid; D009439:Neuraminidase