Chalcones as novel influenza A (H1N1) neuraminidase inhibitors from Glycyrrhiza inflata.
The emergence of highly pathogenic influenza A virus strains, such as the new H1N1 swine influenza (novel influenza), represents a serious threat to global human health. During our course of an anti-influenza screening program on natural products, one new licochalcone G (1) and seven known (2-8) chalcones were isolated as active principles from the acetone extract of Glycyrrhiza inflata. Compounds 3 and 6 without prenyl group showed strong inhibitory effects on various neuraminidases from influenza viral strains, H1N1, H9N2, novel H1N1 (WT), and oseltamivir-resistant novel H1N1 (H274Y) expressed in 293T cells. In addition, the efficacy of oseltamivir with the presence of compound 3 (5 μM) was increased against H274Y neuraminidase. This evidence of synergistic effect makes this inhibitor to have a potential possibility for control of pandemic infection by oseltamivir-resistant influenza virus.
BK21 Project Team, College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759, Republic of Korea.
Trong Tuan
TT
Dao
Phi Hung
PH
Nguyen
Hong Sik
HS
Lee
Eunhee
E
Kim
Junsoo
J
Park
Seong Il
SI
Lim
Won Keun
WK
Oh
D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D047188:Chalcones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology*; D053127:Influenza A Virus, H9N2 Subtype / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009154:Mutation; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D000998:Antiviral Agents; D047188:Chalcones; D004791:Enzyme Inhibitors; C557264:licochalcone G; D009439:Neuraminidase