tetano
Editor, Senior Moderator
Angew Chem Int Ed Engl. 2016 Feb 2. doi: 10.1002/anie.201511361. [Epub ahead of print]
[h=1]Drug Repurposing Identifies Inhibitors of Oseltamivir-Resistant Influenza Viruses.[/h] Bao J[SUP]1[/SUP], Marathe B[SUP]2[/SUP], Govorkova EA[SUP]2[/SUP], Zheng JJ[SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The neuraminidase (NA) inhibitor, oseltamivir, is a widely used anti-influenza drug. However, oseltamivir-resistant H1N1 influenza viruses carrying the H275Y NA mutation spontaneously emerged as a result of natural genetic drift and drug treatment. Because H275Y and other potential mutations may generate a future pandemic influenza strain that is oseltamivir-resistant, alternative therapy options are needed. Herein, we show that a structure-based computational method can be used to identify existing drugs that inhibit resistant viruses, thereby providing a first line of pharmaceutical defense against this possible scenario. We identified two drugs, nalidixic acid and dorzolamide, that potently inhibit the NA activity of oseltamivir-resistant H1N1 viruses with the H275Y NA mutation at very low concentrations, but have no effect on wild-type H1N1 NA even at a much higher concentration, suggesting that the oseltamivir-resistance mutation itself caused susceptibility to these drugs.
? 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[h=4]KEYWORDS:[/h] computational chemistry; drug discovery; drug repurposing; influenza viruses; neuraminidase
PMID: 26833677 [PubMed - as supplied by publisher]
[h=1]Drug Repurposing Identifies Inhibitors of Oseltamivir-Resistant Influenza Viruses.[/h] Bao J[SUP]1[/SUP], Marathe B[SUP]2[/SUP], Govorkova EA[SUP]2[/SUP], Zheng JJ[SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The neuraminidase (NA) inhibitor, oseltamivir, is a widely used anti-influenza drug. However, oseltamivir-resistant H1N1 influenza viruses carrying the H275Y NA mutation spontaneously emerged as a result of natural genetic drift and drug treatment. Because H275Y and other potential mutations may generate a future pandemic influenza strain that is oseltamivir-resistant, alternative therapy options are needed. Herein, we show that a structure-based computational method can be used to identify existing drugs that inhibit resistant viruses, thereby providing a first line of pharmaceutical defense against this possible scenario. We identified two drugs, nalidixic acid and dorzolamide, that potently inhibit the NA activity of oseltamivir-resistant H1N1 viruses with the H275Y NA mutation at very low concentrations, but have no effect on wild-type H1N1 NA even at a much higher concentration, suggesting that the oseltamivir-resistance mutation itself caused susceptibility to these drugs.
? 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[h=4]KEYWORDS:[/h] computational chemistry; drug discovery; drug repurposing; influenza viruses; neuraminidase
PMID: 26833677 [PubMed - as supplied by publisher]