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    Structure-based design and synthesis of triazole-based macrocyclic inhibitors of norovirus protease: Structural, biochemical, spectroscopic, and antiviral studies

    Date
    2016-08-25
    Author
    Weerawarna, Pathum M.
    Kim, Yunjeong
    Kankanamalage, Anushka C. Galasiti
    Damalanka, Vishnu C.
    Lushington, Gerald H.;
    Alliston, Kevin R.
    Mehzabeen, Nurjahan
    Battaile, Kevin P.
    Lovell, Scott
    Chang, Kyeong-Ok
    Groutas, William C.
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    Citation
    Weerawarna, Pathum M.; Kim, Yunjeong; Kankanamalage, Anushka C. Galasiti; Damalanka, Vishnu C.; Lushington, Gerald H.; Alliston, Kevin R.; Mehzabeen, Nurjahan; Battaile, Kevin P.; Lovell, Scott; Chang, Kyeong-Ok; Groutas, William C. 2016. Structure-based design and synthesis of triazole-based macrocyclic inhibitors of norovirus protease: Structural, biochemical, spectroscopic, and antiviral studies. European Journal of Medicinal Chemistry, vol. 119, 25 August 2016:pp 300–318
    Abstract
    Outbreaks of acute gastroenteritis caused by noroviruses constitute a public health concern worldwide. To date, there are no approved drugs or vaccines for the management and prophylaxis of norovirus infections. A potentially effective strategy for the development of norovirus therapeutics entails the discovery of inhibitors of norovirus 3CL protease, an enzyme essential for noroviral replication. We describe herein the structure-based design of the first class of permeable, triazole-based macrocyclic inhibitors of norovirus 3C-like protease, as well as pertinent X-ray crystallographic, biochemical, spectroscopic, and antiviral studies.
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    URI
    http://dx.doi.org/10.1016/j.ejmech.2016.04.013
    http://hdl.handle.net/10057/12302
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