Structure-activity relationship of flavonoids as influenza virus neuraminidase inhibitors and their in vitro anti-viral activities.
Flavonoids are polyphenolic compounds that widely exist in plant kingdom, and the structure-activity relationship (SAR) of 25 flavonoids was studied on neuraminidase (NA) activity of influenza virus. Three typical influenza virus strains A/PR/8/34 (H1N1), A/Jinan/15/90 (H3N2), and B/Jiangshu/10/2003 were used as the source of NAs, the average of IC(50)s of these compounds on these NAs was used in the SAR analysis. The order of potency for NA inhibition was as follows: aurones>flavon(ol)es>isoflavones>flavanon(ol)es and flavan(ol)es. The SAR analysis of flavonoids on influenza virus NAs revealed that for good inhibitory effect, the 4'-OH, 7-OH, C4O, and C2C3 functionalities were essential, and the presence of a glycosylation group greatly reduced NA inhibition. The in vitro anti-viral activities of eight flavonoids were evaluated using a cytopathic effect (CPE) reduction method, the assay results confirmed the SAR as influenza virus neuraminidase inhibitors. The findings of this study provide important information for the exploitation and utilization of flavonoids as NA inhibitors for influenza treatment.
Liu
Ai-Lin
AL
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Wang
Hai-Di
HD
Lee
Simon MingYuen
SM
Wang
Yi-Tao
YT
Du
Guan-Hua
GH
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004285:Dogs; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009975:Orthomyxoviridae / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D005419:Flavonoids; D009439:Neuraminidase