title: Potent inhibitor design against H1N1 swine influenza: structure-based and molecular dynamics analysis for M2 inhibitors from traditional Chinese medicine database.
abstract: The rapid spread of influenza virus subtype H1N1 poses a great threat to million lives worldwide. To search for new anti-influenza compounds, we performed molecular docking and molecular dynamics simulation to identify potential traditional Chinese medicine (TCM) constituents that could block influenza M2 channel activity. Quinic acid, genipin, syringic acid, cucurbitine, fagarine, and methyl isoferulate all have extremely well docking results as compared to control amantadine. Further de novo drug design suggests that derivatives of genipin and methyl isoferulate could have enhanced binding affinity towards M2 channel. Selected molecular dynamics simulations of M2-derivative complexes show stable hydrogen bond interactions between the derivatives and M2 residues, Ser10 and Ala9. To our best knowledge, this is the first study on the anti-viral activity of the above listed TCM compounds.
authors.affiliation: Department of Chinese Medicine, China Medical University Hospital, Taiwan.
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Lin
authors.forename: Tung-Ti
authors.initials: TT
authors.lastname: Chang
authors.forename: Mao-Feng
authors.initials: MF
authors.lastname: Sun
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Chen
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Kun-Lung
authors.initials: KL
authors.lastname: Chang
authors.forename: Mark
authors.initials: M
authors.lastname: Fisher
authors.forename: Calvin Yu-Chian
authors.initials: CY
authors.lastname: Chen
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016208:Databases, Factual; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy*; D008516:Medicine, Chinese Traditional; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D034421:Sus scrofa; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D014763:Viral Matrix Proteins