Antiviral activity of Isatis indigotica root-derived clemastanin B against human and avian influenza A and B viruses in vitro.

Clemastanin B, 7S,8R,8'R-(-)-lariciresinol-4,4'-bis-O-β-D-glucopyranoside, is one of the major lignans extracted from Isatis indigotica root (IIR). In this study, the anti-influenza activities of clemastanin B were evaluated in vitro. Clemastanin B was found to inhibit different subtypes of human (H1N1, including swine-origin H1N1; H3N2 and influenza B) and avian influenza viruses (H6N2, H7N3, H9N2) at different magnitudes of activity (IC50 0.087-0.72 mg/ml) while this compound was inactive against respiratory syncytial virus (RSV), adenovirus 3 (ADV3), parainfluenza virus 3 (PIV3), enterovirus 71 (EV71) and human rhinovirus (HRV). An apparent virus titer reduction was detected when MDCK cells were treated with clemastanin B after viral infection, particularly at the early stage, and the ribonucleoprotein (RNP) of the influenza virus was retained in the nucleus after treatment with clemastanin B. These results demonstrated that clemastanin B targets viral endocytosis, uncoating or RNP export from the nucleus. Furthermore, treatment with clemastanin B did not easily result in the emergence of viral drug resistance. The effects of clemastanin B demonstrated in this study may promote the antiviral study of IIR, but additional studies are required to define the anti-influenza mechanism(s).

[1]  A. Shetty,et al.  Peramivir for the treatment of influenza , 2012, Expert review of anti-infective therapy.

[2]  Tzou-Yien Lin,et al.  Mechanism of action of the suppression of influenza virus replication by Ko-Ken Tang through inhibition of the phosphatidylinositol 3-kinase/Akt signaling pathway and viral RNP nuclear export. , 2011, Journal of ethnopharmacology.

[3]  L. Finelli,et al.  Emergence of a novel swine-origin influenza A (H1N1) virus in humans. , 2009, The New England journal of medicine.

[4]  H. Ho,et al.  Antiviral effect of epigallocatechin gallate on enterovirus 71. , 2009, Journal of agricultural and food chemistry.

[5]  Yasuhiko Ito,et al.  In vitro inhibition of human influenza A virus infection by fruit-juice concentrate of Japanese plum (Prunus mume SIEB. et ZUCC). , 2008, Biological & pharmaceutical bulletin.

[6]  R. Silverman,et al.  Inhibition of human parainfluenza virus type 3 infection by novel small molecules. , 2008, Antiviral research.

[7]  D. Miyamoto,et al.  Clarithromycin inhibits progeny virus production from human influenza virus-infected host cells. , 2008, Biological & pharmaceutical bulletin.

[8]  Virginia Korte,et al.  A polyphenol rich plant extract, CYSTUS052, exerts anti influenza virus activity in cell culture without toxic side effects or the tendency to induce viral resistance. , 2007, Antiviral research.

[9]  N. Cox,et al.  Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide. , 2007, The Journal of infectious diseases.

[10]  Thorsten Wolff,et al.  Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF‐κB‐inhibiting activity , 2007, Cellular microbiology.

[11]  H. Klenk,et al.  Membrane Accumulation of Influenza A Virus Hemagglutinin Triggers Nuclear Export of the Viral Genome via Protein Kinase Cα-mediated Activation of ERK Signaling* , 2006, Journal of Biological Chemistry.

[12]  J. Taubenberger The origin and virulence of the 1918 "Spanish" influenza virus. , 2006, Proceedings of the American Philosophical Society.

[13]  N. Cox,et al.  Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States. , 2006, JAMA.

[14]  Yi Guan,et al.  Oseltamivir resistance during treatment of influenza A (H5N1) infection. , 2005, The New England journal of medicine.

[15]  Hideo Goto,et al.  Avian flu: Isolation of drug-resistant H5N1 virus , 2005, Nature.

[16]  Xiyan Xu,et al.  Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern , 2005, The Lancet.

[17]  Jinyong Peng,et al.  Isolation and purification of clemastanin B and indigoticoside A from Radix Isatidis by high-speed counter-current chromatography , 2005, Journal of Chromatography A.

[18]  P. Palese,et al.  Influenza: old and new threats , 2004, Nature Medicine.

[19]  Thorsten Wolff,et al.  MEK inhibition impairs influenza B virus propagation without emergence of resistant variants , 2004, FEBS letters.

[20]  T. Suzutani,et al.  Anti‐influenza virus activity of crude extract of Ribes nigrum L. , 2003, Phytotherapy research : PTR.

[21]  Thorsten Wolff,et al.  Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade , 2001, Nature Cell Biology.

[22]  F. Hayden,et al.  In vitro activity of pleconaril and AG7088 against selected serotypes and clinical isolates of human rhinoviruses. , 2000, Antiviral research.

[23]  H. Kizu,et al.  Studies on the constituents of Clematis species. VI. The constituents of Clematis stans Sieb. et Zucc. , 1995, Chemical & pharmaceutical bulletin.

[24]  M. Trousdale,et al.  Inhibition of human adenoviruses by 1-(2′-hydroxy-5′-methoxybenzylidene)amino-3-hydroxyguanidine tosylate , 1994, Antiviral Research.

[25]  M. Perkins,et al.  Primary respiratory syncytial virus infection in mice , 1988, Journal of medical virology.

[26]  S. Natori,et al.  Isolation of 2-hydroxy-3-butenyl thiocyanate, epigoitrin, and adenosine from 'Banlangen', Isatis indigotica root. , 1981, Planta medica.

[27]  L. Reed,et al.  A SIMPLE METHOD OF ESTIMATING FIFTY PER CENT ENDPOINTS , 1938 .

[28]  Liu Jun Effects of Banlangen polysaccharide on mice resistance to Influenza virus infection , 2008 .

[29]  Jia Xiaobin,et al.  Thinking in studies on antiviral material base of Radix Isatidis , 2008 .

[30]  Xu Li,et al.  Antivirus Constituents of Radix of Isatis indigotica , 2005 .

[31]  R. Wong,et al.  Inhibition of RANTES expression by indirubin in influenza virus-infected human bronchial epithelial cells. , 2004, Biochemical pharmacology.

[32]  Yu-Ling Ho,et al.  Studies on the Homonymic Chinese Crude Drug Species in Taiwan Evaluation of the Quality of Da-Ching-Yeh and Ching-Dai , 2001 .

[33]  L. Li,et al.  [Study of quality control on herbal drugs and preparations of daqingye and banlangen]. , 1993, Yao xue xue bao = Acta pharmaceutica Sinica.

[34]  F. Hayden,et al.  Emergence and transmission of influenza A viruses resistant to amantadine and rimantadine. , 1992, Current topics in microbiology and immunology.