These authors contributed equally to this paper.
Amaryllidaceae alkaloids inhibit nuclear-to-cytoplasmic export of ribonucleoprotein (RNP) complex of highly pathogenic avian influenza virus H5N1
Article first published online: 8 NOV 2012
© 2012 John Wiley & Sons Ltd
Influenza and Other Respiratory Viruses
Volume 7, Issue 6, pages 922–931, November 2013
How to Cite
He, J., Qi, W.-B., Wang, L., Tian, J., Jiao, P.-R., Liu, G.-Q., Ye, W.-C. and Liao, M. (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: 922–931. doi: 10.1111/irv.12035
- Issue published online: 5 NOV 2013
- Article first published online: 8 NOV 2012
- Accepted 25 September 2012. Published online 08 November 2012.
- National Natural Science Foundation. Grant Numbers: 81001375, 81273391
- Natural Science Foundation. Grant Number: 10251064201000004
- National Broiler Industry. Grant Number: nycytx-42-G3-03
- Chinese Universities. Grant Number: IRT0723
- New Century Excellent Talents in University. Grant Number: NCET-06-0752
- Science and Technology Projects of Guangdong Province. Grant Number: 20100206
- Amaryllidaceae alkaloid;
- H5N1 influenza A virus;
- vRNP export
Please cite this paper as: He et al. (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.
Background 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 Lycoris radiata, are a potential source of new antiviral agents.
Objective To test 15 Amaryllidaceae alkaloids isolated from the bulbs of L. radiata in vitro for antiviral activities against influenza virus type A, A/Chicken/GuangDong/178/2004 (H5N1, 178).
Methods 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.
Results Among the alkaloids, lycorine (AA1), hippeastrine (AA2), hemanthamine (AA3) and 11-hydroxy vittatine (AA4) exhibited antiviral activities, with EC90 values of 0·52, 82·07, 4·15, and 13·45 μm, respectively. These compounds did not affect the function of the outer membrane proteins or the viral entry process and viral RNP activity. As AA1 and AA3 exhibited stronger antiviral activities, they were further analyzed. Intracellular nucleoprotein (NP) localization showed that AA1 and AA3 inhibited the RNP complex in the nucleus at an early stage of a single-round and multi-round of replication.
Conclusion Four Amaryllidaceae alkaloids were first determined that could exert anti-influenza activities after virus entry into cells. Furthermore, AA1 and AA3 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.