Antiviral effect and mechanism of Phillyrin and its reformulated FS21 against influenza

作者全名："Chen, Yan; Wu, Cunjin; Li, Huifen; Powell, Harrison; Chen, Allison; Zhu, Guodong; Cong, Weihong; Fu, Li; Pekosz, Andrew; Leng, Sean X. X."

作者地址："[Chen, Yan] Chongqing Med Univ, Affiliated Hosp 1, Dept Geriatr, Chongqing, Peoples R China; [Wu, Cunjin] Tianjin Med Univ, Hosp 2, Dept Geriatr, Tianjin, Peoples R China; [Li, Huifen; Powell, Harrison; Chen, Allison; Pekosz, Andrew; Leng, Sean X. X.] Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA; [Li, Huifen; Powell, Harrison; Chen, Allison; Leng, Sean X. X.] Johns Hopkins Univ, Dept Med, Div Geriatr Med & Gerontol, Sch Med, Baltimore, MD USA; [Li, Huifen; Leng, Sean X. X.] Johns Hopkins Ctr Aging & Immune Remodeling, Baltimore, MD USA; [Zhu, Guodong] Guangzhou Geriatr Hosp, Guangzhou, Peoples R China; [Cong, Weihong] China Acad Chinese Med Sci, Xiyuan Hosp, Natl Clin Res Ctr Chinese Med, Beijing, Peoples R China; [Fu, Li] Dalian Fusheng Nat Med Dev Co Ltd, Dalian, Peoples R China; [Leng, Sean X. X.] Johns Hopkins Univ, Johns Hopkins Ctr Aging & Immune Remodeling, Div Geriatr Med & Gerontol, Dept Med,Sch Med, Baltimore, MD 21218 USA"

通信作者："Pekosz, A; Leng, SX (通讯作者)，Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.; Fu, L (通讯作者)，Dalian Fusheng Nat Med Dev Co Ltd, Dalian, Peoples R China.; Leng, SX (通讯作者)，Johns Hopkins Univ, Johns Hopkins Ctr Aging & Immune Remodeling, Div Geriatr Med & Gerontol, Dept Med,Sch Med, Baltimore, MD 21218 USA."

来源：INFLUENZA AND OTHER RESPIRATORY VIRUSES

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000940813400001

JCR分区：Q1

影响因子：4.3

年份：2023

卷号：17

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：antiviral effect; FS21; influenza; influenza RNA polymerase inhibition; Phillyrin

摘要："BackgroundInfluenza virus causes significant morbidity and mortality with pandemic threat. Oleaceae Fructus Forsythiae is a medicinal herb. This study aimed to investigate antiviral effect of Phillyrin, a purified bioactive compound from this herb, and its reformulated preparation FS21 against influenza and its mechanism. MethodsMadin-Darby Canine Kidney (MDCK) cells were infected by one of six influenza viruses: five influenza A viruses (IAVs: three H1N1 and two H3N2) and one influenza B virus (IBV). Virus-induced cytopathic effects were observed and recorded under microscope. Viral replication and mRNA transcription were evaluated by quantitative polymerase chain reaction (qPCR) and protein expression by Western blot. Infectious virus production was assessed using TCID50 assay, and IC50 was calculated accordingly. Pretreatment and time-of-addition experiments with Phillyrin or FS21 added 1 h before or in early (0-3 h), mid (3-6 h), or late (6-9 h) stages of viral infection were performed to assess their antiviral effects. Mechanistic studies included hemagglutination and neuraminidase inhibition, viral binding and entry, endosomal acidification, and plasmid-based influenza RNA polymerase activity. ResultsPhillyrin and FS21 had potent antiviral effects against all six IAV and IBV in a dose-dependent manner. Mechanistic studies showed that both suppressed influenza viral RNA polymerase with no effect on virus-mediated hemagglutination inhibition, viral binding or entry, endosomal acidification, or neuraminidase activity. ConclusionsPhillyrin and FS21 have broad and potent antiviral effects against influenza viruses with inhibition of viral RNA polymerase as the distinct antiviral mechanism."

基金机构："Johns Hopkins Center of Excellence in Influenza Research and Surveillance [N2772201400007C, T32 AI007417]; National Institute of Health (NIH)/National Institute of Allergy and Infectious Diseases [R01 AI108907, U01 AI165826]; Johns Hopkins Center of Excellence in Influenza Research and Surveillance HHS; Howard and Abby Milstein Foundation; Milstein Medical Asian American Partnership (MMAAP) Foundation; Johns Hopkins Center for Innovative Medicine"

基金资助正文："Johns Hopkins Center of Excellence in Influenza Research and Surveillance, Grant/Award Numbers: N2772201400007C, T32 AI007417; National Institute of Health (NIH)/National Institute of Allergy and Infectious Diseases, Grant/Award Numbers: R01 AI108907, U01 AI165826; Johns Hopkins Center of Excellence in Influenza Research and Surveillance HHS; Howard and Abby Milstein Foundation; Milstein Medical Asian American Partnership (MMAAP) Foundation; Johns Hopkins Center for Innovative Medicine"