title: Characterization of the binding affinities of peramivir and oseltamivir carboxylate to the neuraminidase enzyme.
abstract: With the continued threat of morbidity and mortality from influenza and the development of resistance to influenza antiviral drugs, there is increasing interest in new treatments, such as the investigational intravenous drug peramivir, and in combination treatments. In this study, we determined the impact of oseltamivir carboxylate on the binding affinity of peramivir/neuraminidase (NA) enzyme complex and vice versa. Influenza NA was incubated with peramivir and oseltamivir carboxylate alone and in combination. Dissociation rates of the enzyme-inhibitor complex measured in the presence of NA substrate for peramivir alone and the combination were similar, suggesting that peramivir competitively inhibits the neuraminidase enzyme and that oseltamivir carboxylate when added to peramivir does not impact the binding affinity of peramivir to the NA enzyme.
authors: Department of Biological Sciences, BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive, Birmingham, AL 35244, USA. sbantia@biocryst.com
authors: Shanta
authors: S
authors: Bantia
authors: Ramanda
authors: R
authors: Upshaw
authors: Y S
authors: YS
authors: Babu
mesh_terms: D000146:Acids, Carbocyclic; D000998:Antiviral Agents / Q000494:pharmacology; D002021:Buffers; D003517:Cyclopentanes / Q000494:pharmacology*; D004338:Drug Combinations; D004347:Drug Interactions; D024882:Drug Resistance, Viral / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000201:enzymology; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053139:Oseltamivir / Q000031:analogs & derivatives* / Q000494:pharmacology; D011485:Protein Binding; D012996:Solutions; D013050:Spectrometry, Fluorescence; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D002021:Buffers; D003517:Cyclopentanes; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D006146:Guanidines; D012996:Solutions; D014764:Viral Proteins; D053139:Oseltamivir; D009439:Neuraminidase; C535162:oseltamivir carboxylate; C414210:peramivir