Amaryllidaceae alkaloids inhibit nuclear‐to‐cytoplasmic export of ribonucleoprotein (RNP) complex of highly pathogenic avian influenza virus H5N1. Issue 6 (8th November 2012)

• Record Type: Journal Article
• Authors: He, Jun; Qi, Wen‐Bao; Wang, Lei; Tian, Jin; Jiao, Pei‐Rong; Liu, Guo‐Qian; Ye, Wen‐Cai; Liao, Ming
• Is Part Of: Influenza and other respiratory viruses. Volume 7:Issue 6(2013:Nov.)
• Page Start: 922
• Page End: 931
• Publication Date: 2012-11-08
• Subjects: Influenza -- Periodicals; Respiratory infections -- Periodicals; Virus diseases -- Periodicals; Influenza, Human -- Periodicals; Respiratory Tract Diseases -- Periodicals; Virus Diseases -- Periodicals; Grippe -- Périodiques; Appareil respiratoire -- Infections -- Périodiques; Maladies à virus -- Périodiques; 616.203
• DOI: 10.1111/irv.12035
• Languages: English
• ISSNs: 1750-2640

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>Please cite this paper as:</italic> He <italic>et al.</italic> (2013) Amaryllidaceae alkaloids inhibit nuclear‐to‐cytoplasmic export of ribonucleoprotein (RNP) complex of highly pathogenic avian influenza virus H5N1. Influenza and Other Respiratory Viruses 7(6), 922–931.</p> <p> <bold>Background </bold> Few drugs are currently licensed to treat influenza A infection, and new therapies are needed, especially for highly pathogenic strains. Traditional medicinal plants, such as <italic>Lycoris radiata</italic>, are a potential source of new antiviral agents.</p> <p> <bold>Objective </bold> To test 15 Amaryllidaceae alkaloids isolated from the bulbs of <italic>L. radiata in vitro</italic> for antiviral activities against influenza virus type A, A/Chicken/GuangDong/178/2004 (H5N1, 178).</p> <p> <bold>Methods </bold> Antiviral activities of the compounds were tested in time‐of‐addition assays, hemagglutination inhibition (HI) assays, neuraminidase (NA) activity assays, and viral entry inhibition assays using H5N1‐HIV pseudoviruses. Effects of the compounds on localization and activity of the viral ribonucleoprotein (RNP) were determined by immunofluorescence and an RNP minigenome assay, respectively.</p> <p> <bold>Results </bold> Among the alkaloids, lycorine (<bold>AA1</bold>), hippeastrine (<bold>AA2</bold>), hemanthamine (<bold>AA3</bold>) and 11‐hydroxy vittatine (<bold>AA4</bold>) exhibited antiviral activities, with EC<sub>90</sub> values of 0·52, 82·07, 4·15, and 13·45 μ<sc>m</sc>, respectively. These compounds did not affect the function of the outer membrane proteins or the viral entry process and viral RNP activity. As <bold>AA1</bold> and <bold>AA3</bold> exhibited stronger antiviral activities, they were further analyzed. Intracellular nucleoprotein (NP) localization showed that <bold>AA1</bold> and <bold>AA3</bold> inhibited the RNP complex in the nucleus at an early stage of a single‐round and multi‐round of replication.</p> <p> <bold>Conclusion </bold> Four Amaryllidaceae alkaloids were first determined that could exert anti‐influenza activities after virus entry into cells. Furthermore, <bold>AA1</bold> and <bold>AA3</bold> could inhibit nuclear‐to‐cytoplasmic export of the RNP complex of virus replication. Thus, these compounds may be developed further as anti‐influenza drug candidates.</p> </abstract>