• Login
    View Item 
    •   Shocker Open Access Repository Home
    • Fairmount College of Liberal Arts and Sciences
    • Chemistry and Biochemistry
    • CHEM Faculty Scholarship
    • CHEM Faculty Publications
    • View Item
    •   Shocker Open Access Repository Home
    • Fairmount College of Liberal Arts and Sciences
    • Chemistry and Biochemistry
    • CHEM Faculty Scholarship
    • CHEM Faculty Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Potent protease inhibitors of highly pathogenic lagoviruses: Rabbit hemorrhagic disease virus and European brown hare syndrome virus

    View/Open
    Open access PDF (2.369Mb)
    Date
    2022-06-29
    Author
    Perera, Krishani Dinali
    Johnson, David
    Lovell, Scott
    Groutas, William C.
    Chang, Kyeong-Ok
    Kim, Yunjeong
    Metadata
    Show full item record
    Citation
    Perera Krishani, D., Johnson, D., Lovell, S., Groutas William, C., Chang, K.-O., & Kim, Y. (2022). Potent Protease Inhibitors of Highly Pathogenic Lagoviruses: Rabbit Hemorrhagic Disease Virus and European Brown Hare Syndrome Virus. Microbiology Spectrum, 10(4), e00142-00122. https://doi.org/10.1128/spectrum.00142-22
    Abstract
    Rabbit hemorrhagic disease (RHD) and European brown hare syndrome (EBHS) are highly contagious diseases caused by lagoviruses in the Caliciviridae family. These infectious diseases are associated with high mortality and a serious threat to domesticated and wild rabbits and hares, including endangered species such as riparian brush rabbits (Sylvilagus bachmani riparius). In the United States (U.S.), only isolated cases of RHD had been reported until Spring 2020. However, RHD caused by GI.2/rabbit hemorrhagic disease virus (RHDV)2/b was unexpectedly reported in April 2020 in New Mexico and has subsequently spread to several U.S. states, infecting wild rabbits and hares and making it highly likely that RHD will become endemic in the U.S. Vaccines are available for RHD; however, there is no specific treatment for this disease. Lagoviruses encode a 3C-like protease (3CLpro), which is essential for virus replication and a promising target for antiviral drug development. We have previously generated focused small-molecule libraries of 3CLpro inhibitors and demonstrated the in vitro potency and in vivo efficacy of some protease inhibitors against viruses encoding 3CLpro, including caliciviruses and coronaviruses. Here, we report the development of the enzyme and cell-based assays for the 3CLpro of GI.1c/RHDV, recombinant GI.3P-GI.2 (RHDV2/b), and GII.1/European brown hare syndrome virus (EBHSV) as well as the identification of potent lagovirus 3CLpro inhibitors, including GC376, a protease inhibitor being developed for feline infectious peritonitis. In addition, structure-activity relationship study and homology modeling of the 3CLpro and inhibitors revealed that lagovirus 3CLpro share similar structural requirements for inhibition with other calicivirus 3CLpro.
    Description
    This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Click on the DOI to access the publisher's version of this article.
    URI
    https://doi.org/10.1128/spectrum.00142-22
    https://soar.wichita.edu/handle/10057/24865
    Collections
    • CHEM Faculty Publications

    Browse

    All of Shocker Open Access RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsBy TypeThis CollectionBy Issue DateAuthorsTitlesSubjectsBy Type

    My Account

    LoginRegister

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    DSpace software copyright © 2002-2023  DuraSpace
    DSpace Express is a service operated by 
    Atmire NV