title: Inhibitory effect and possible mechanism of action of patchouli alcohol against influenza A (H2N2) virus.
abstract: In the present study, the anti-influenza A (H2N2) virus activity of patchouli alcohol was studied in vitro, in vivo and in silico. The CC₅₀ of patchouli alcohol was above 20 µM. Patchouli alcohol could inhibit influenza virus with an IC₅₀ of 4.03 ± 0.23 µM. MTT assay showed that the inhibition by patchouli alcohol appears strongly after penetration of the virus into the cell. In the influenza mouse model, patchouli alcohol showed obvious protection against the viral infection at a dose of 5 mg/kg/day. Flexible docking and molecular dynamic simulations indicated that patchouli alcohol was bound to the neuraminidase protein of influenza virus, with an interaction energy of -40.38 kcal mol⁻¹. The invariant key active-site residues Asp151, Arg152, Glu119, Glu276 and Tyr406 played important roles during the binding process. Based on spatial and energetic criteria, patchouli alcohol interfered with the NA functions. Results presented here suggest that patchouli alcohol possesses anti-influenza A (H2N2) virus properties, and therefore is a potential source of anti-influenza agents for the pharmaceutical industry.
authors.affiliation: Department of Endoscopy, the Third Affiliated Hospital, Harbin Medical University, Harbin 150040, China.
authors.forename: Huaxing
authors.initials: H
authors.lastname: Wu
authors.forename: Beili
authors.initials: B
authors.lastname: Li
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Jin
authors.forename: Guonian
authors.initials: G
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D053121:Influenza A Virus, H2N2 Subtype / Q000187:drug effects* / Q000254:growth & development; D020128:Inhibitory Concentration 50; D051379:Mice; D008815:Mice, Inbred Strains; D056004:Molecular Dynamics Simulation; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000821:virology; D053139:Oseltamivir / Q000494:pharmacology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D015996:Survival Rate; D013816:Thermodynamics; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D012717:Sesquiterpenes; D053139:Oseltamivir; D009439:Neuraminidase; C052983:patchouli alcohol