title: Oseltamivir activity against avian influenza H9N2 strain with different point mutations in their neuraminidase.
abstract: The present study has two aims: to optimize the antiviral activity of oseltamivir in chicken embryos against an avian influenza-H9N2 strain (P0) and to apply the optimized protocol for studying the drug susceptibility of 4 H9N2 mutants (M1, M2, M3, and M4). As for the first aim, oseltamivir antiviral activity was monitored upon its delivery into 9-day-old chicken embryo at a concentration of 0.27 mg/100 μl, against 7 doses of the P0 strain, ranging between 1.2 x 10(-5) and 2.0 Hemagglutination (HA) units. Oseltamivir showed its highest efficacy in reduction of viral propagation (95% reduction in HA titer) (P 〈0.05), when the inoculum level contained a minimum HA units of 1.2 x 10(-5). For the second aim of this study, the application of the 1.2 x 10-(5) HA units of the virus in inocula for the evaluation of oseltamivir-antiviral effect against the 4 H9N2 mutants revealed an emergence of a resistant mutant (M1), associated with 2 adjacent point mutations in its neuraminidase (N) amino acid (aa) sequence at positions 46 and 47. The other 3 mutants maintained a variable sensitivity to oseltamivir, resulting in the following reduction in HA titers: M2 (82.9%), M3 (61.5%), and M4 (100.0%). How the point mutations of the neuraminidase sequences affected the susceptibility of H9N2 virus to oseltamivir is still to be determined and deserve further investigations.
authors.affiliation: Biochemistry Department, Faculty of Science and Experimental Biochemistry Unit, King Fahad Medical Research Center, King Abdul Aziz University, P.O. Box 80216, Jeddah, Saudi Arabia.
authors.forename: Taha
authors.initials: T
authors.lastname: Kumosani
authors.forename: Diana
authors.initials: D
authors.lastname: Ahmadieh
authors.forename: Houssam
authors.initials: H
authors.lastname: Shaib
authors.forename: Shadi
authors.initials: S
authors.lastname: Hamadeh
authors.forename: Lina
authors.initials: L
authors.lastname: Jaber
authors.forename: Steve
authors.initials: S
authors.lastname: Harakeh
authors.forename: Archana
authors.initials: A
authors.lastname: Iyer
authors.forename: Esam
authors.initials: E
authors.lastname: Azhar
authors.forename: Elie
authors.initials: E
authors.lastname: Barbour
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001717:Birds; D002642:Chick Embryo; D053127:Influenza A Virus, H9N2 Subtype / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D005585:Influenza in Birds / Q000188:drug therapy; D009439:Neuraminidase / Q000235:genetics*; D053139:Oseltamivir / Q000494:pharmacology* / Q000627:therapeutic use; D017354:Point Mutation
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; D009439:Neuraminidase