title: Inhibition of neuraminidase by Ganoderma triterpenoids and implications for neuraminidase inhibitor design.
abstract: Neuraminidase (NA) inhibitors are the dominant antiviral drugs for treating influenza in the clinic. Increasing prevalence of drug resistance makes the discovery of new NA inhibitors a high priority. Thirty-one triterpenoids from the medicinal mushroom Ganoderma lingzhi were analyzed in an in vitro NA inhibition assay, leading to the discovery of ganoderic acid T-Q and TR as two inhibitors of H5N1 and H1N1 NAs. Structure-activity relationship studies revealed that the corresponding triterpenoid structure is a potential scaffold for the design of NA inhibitors. Using these triterpenoids as probes we found, through further in silico docking and interaction analysis, that interactions with the amino-acid residues Arg292 and/or Glu119 of NA are critical for the inhibition of H5N1 and H1N1. These findings should prove valuable for the design and development of NA inhibitors.
authors: Department of Agro-environmental Sciences, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors: Qinchang
authors: Q
authors: Zhu
authors: Department of Agro-environmental Sciences, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors: Tran Hai
authors: TH
authors: Bang
authors: Department of Biological and Environmental Chemistry, Kinki University, Kayanomori 11-6, Iizuka, Fukuoka 820-8555, Japan.
authors: Koichiro
authors: K
authors: Ohnuki
authors: Toyotanshien Co Ltd. 3-1 Kitanijyonishi, Chuo-ku, Sapporo 060-0002, Japan.
authors: Takashi
authors: T
authors: Sawai
authors: Toyotanshien Co Ltd. 3-1 Kitanijyonishi, Chuo-ku, Sapporo 060-0002, Japan.
authors: Ken
authors: K
authors: Sawai
authors: Department of Agro-environmental Sciences, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors: Kuniyoshi
authors: K
authors: Shimizu
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D004789:Enzyme Activation; D032902:Ganoderma / Q000378:metabolism*; D008956:Models, Chemical; D062105:Molecular Docking Simulation; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D014315:Triterpenes; D009439:Neuraminidase