Shared more. Cited more. Safe forever.
    • advanced search
    • submit works
    • about
    • help
    • contact us
    • login
    View Item 
    •   MOspace Home
    • University of Missouri System
    • Missouri Summits
    • Missouri Regional Life Sciences Summit 2010
    • Abstracts (Missouri Regional Life Sciences Summit 2010)
    • View Item
    •   MOspace Home
    • University of Missouri System
    • Missouri Summits
    • Missouri Regional Life Sciences Summit 2010
    • Abstracts (Missouri Regional Life Sciences Summit 2010)
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    advanced searchsubmit worksabouthelpcontact us

    Browse

    All of MOspaceCommunities & CollectionsDate IssuedAuthor/ContributorTitleIdentifierThesis DepartmentThesis AdvisorThesis SemesterThis CollectionDate IssuedAuthor/ContributorTitleIdentifierThesis DepartmentThesis AdvisorThesis Semester

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular AuthorsStatistics by Referrer

    Discovery and Mechanistic Characterization of Novel SARS Coronavirus Inhibitors that Block Viral Entry [abstract]

    Adedeji, Adeyemi
    Severson, William
    Jonsson, Colleen
    Michailidis, Eleftherios
    Marchand, Bruno
    Singh, Kamlendra
    Weiss, Susan R.
    Sarafianos, Stefan G.
    View/Open
    [PDF] DiscoveryMechanisticCharacterizationNovel[abstract].pdf (23.51Kb)
    Date
    2010-03
    Contributor
    University of Missouri (System)
    Format
    Other
    Abstract
    Metadata
    [+] Show full item record
    Abstract
    Severe acute respiratory syndrome (SARS) is an infectious and highly contagious disease that is caused by SARS-associated coronavirus (SARS-CoV). Viral entry is a key target step for therapies because it can prevent the propagation of virus at early stages of the disease. We used a cell-based assay to identify inhibitors of SARS-CoV entry. We prepared a pseudotyped virus in which the core is from HIV and envelop is from the SARS-CoV (HIV-luc/SARS env). This pseudotyped virus was used to infect, 293T cells expressing the receptor for SARS-CoV, Aangiotensin-converting enzyme-2 (ACE2). Using this assay we screened a chemical library of more than 2000 compounds and identified three compounds that specifically inhibit entry of the HIV-luc/SARS env. These compounds did not inhibit another pseudotyped virus which had same core from HIV but envelop was from Vesicular Stomatitis Virus. The compounds had strong potencies (EC50s were 2.9, 4.8 and 5.8 µM) and low cytotoxicities (high CC50s) resulting in promising Selectivity Indices (CC50/EC50 were >175, >65, and >86, respectively). Importantly, the compounds were found to have excellent antiviral activities, blocking SARS-CoV replication at low nM concentrations. Only one of the compounds was a moderate inhibitor of cathepsin L, a cellular protease whose activity is required to process the SARS-CoV env glycoprotein (Spike) and allow viral entry. Moreover, none of the compounds affects the cleavage activity of furin, another host protease, which may also be involved in SARS-CoV entry. Using a flow cytometry binding assay, we found that all three compounds decrease binding of the SARS-CoV Spike receptor binding domain to ACE2 receptor expressed on the surface of 293Tcells. Hence, we have discovered three promising compounds as the first small molecule inhibitors that can block receptor-dependent entry of SARS-CoV.
    URI
    http://hdl.handle.net/10355/6318
    Part of
    Abstracts (Missouri Regional Life Sciences Summit 2010)
    Collections
    • Abstracts (Missouri Regional Life Sciences Summit 2010)
    • Molecular Microbiology and Immunology presentations (MU)

    Send Feedback
    hosted by University of Missouri Library Systems
     

     


    Send Feedback
    hosted by University of Missouri Library Systems