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    Improving Viral Protease Inhibitors to Counter Drug Resistance

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    Authors
    Yilmaz, Nese Kurt
    Swanstrom, Ronald I.
    Schiffer, Celia A.
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Document Type
    Journal Article
    Publication Date
    2016-04-15
    Keywords
    Biochemistry
    Medicinal Chemistry and Pharmaceutics
    Medicinal-Pharmaceutical Chemistry
    Molecular Biology
    Structural Biology
    Virology
    
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    Link to Full Text
    http://dx.doi.org/10.1016/j.tim.2016.03.010
    Abstract
    Drug resistance is a major problem in health care, undermining therapy outcomes and necessitating novel approaches to drug design. Extensive studies on resistance to viral protease inhibitors, particularly those of HIV-1 and hepatitis C virus (HCV) protease, revealed a plethora of information on the structural and molecular mechanisms underlying resistance. These insights led to several strategies to improve viral protease inhibitors to counter resistance, such as exploiting the essential biological function and leveraging evolutionary constraints. Incorporation of these strategies into structure-based drug design can minimize vulnerability to resistance, not only for viral proteases but for other quickly evolving drug targets as well, toward designing inhibitors one step ahead of evolution to counter resistance with more intelligent and rational design.
    Source
    Trends Microbiol. 2016 Apr 15. pii: S0966-842X(16)30002-6. doi: 10.1016/j.tim.2016.03.010. [Epub ahead of print] Link to article on publisher's website
    DOI
    10.1016/j.tim.2016.03.010
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/48864
    PubMed ID
    27090931
    Related Resources
    Link to article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.tim.2016.03.010
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