title: From neuraminidase inhibitors to conjugates: a step towards better anti-influenza drugs?
abstract: For the treatment of seasonal flu and possible pandemic infections the development of new anti-influenza drugs that have good bioavailability against a broad spectrum of influenza viruses including the resistant strains is needed. In this review, we summarize previous methods for the structural modification of zanamivir, a potent neuraminidase inhibitor that has rare drug resistance, in order to develop effective anti-influenza drugs. We also report recent research into the design of multivalent zanamivir drugs and bifunctional zanamivir conjugates, some of which have shown better efficacy in animal experiments. As a step towards developing improved antivirals, conjugating anti-influenza drugs with anti-inflammatory agents can improve oral bioavailability and also exert synergistic effect in influenza therapy.
authors.affiliation: Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Chung-Kai
authors.initials: CK
authors.lastname: Cheng
authors.forename: Chen-Hsuan
authors.initials: CH
authors.lastname: Tsai
authors.forename: Jiun-Jie
authors.initials: JJ
authors.lastname: Shie
authors.forename: Jim-Min
authors.initials: JM
authors.lastname: Fang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D058990:Molecular Targeted Therapy; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D009975:Orthomyxoviridae / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D053243:Zanamivir / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D009439:Neuraminidase; D053243:Zanamivir