@article{uoadl:2980730,
    volume = "7",
    number = "7",
    pages = "1245-1260",
    journal = "ACS Central Science",
    issn = "2374-7943, 2374-7951",
    keywords = "Energy transfer;  Fluorescence;  Molecular dynamics;  Papain, Antiviral activities;  Conformational change;  Fluorescence resonance energy transfer;  High throughput screening;  Lead optimization;  Molecular dynamics simulations;  Protease inhibitor;  X ray crystal structures, Crystal structure",
    BIBTEX_ENTRY = "article",
    year = "2021",
    author = "Ma, C. and Sacco, M.D. and Xia, Z. and Lambrinidis, G. and Townsend, J.A. and Hu, Y. and Meng, X. and Szeto, T. and Ba, M. and Zhang, X. and Gongora, M. and Zhang, F. and Marty, M.T. and Xiang, Y. and Kolocouris, A. and Chen, Y. and Wang, J.",
    abstract = "The papain-like protease (PLpro) of SARS-CoV-2 is a validated antiviral drug target. Through a fluorescence resonance energy transfer-based high-throughput screening and subsequent lead optimization, we identified several PLpro inhibitors including Jun9-72-2 and Jun9-75-4 with improved enzymatic inhibition and antiviral activity compared to GRL0617, which was reported as a SARS-CoV PLpro inhibitor. Significantly, we developed a cell-based FlipGFP assay that can be applied to predict the cellular antiviral activity of PLpro inhibitors in the BSL-2 setting. X-ray crystal structure of PLpro in complex with GRL0617 showed that binding of GRL0617 to SARS-CoV-2 induced a conformational change in the BL2 loop to a more closed conformation. Molecular dynamics simulations showed that Jun9-72-2 and Jun9-75-4 engaged in more extensive interactions than GRL0617. Overall, the PLpro inhibitors identified in this study represent promising candidates for further development as SARS-CoV-2 antivirals, and the FlipGFP-PLpro assay is a suitable surrogate for screening PLpro inhibitors in the BSL-2 setting. ©",
    title = "Discovery of SARS-CoV-2 Papain-like Protease Inhibitors through a Combination of High-Throughput Screening and a FlipGFP-Based Reporter Assay",
    doi = "10.1021/ACSCENTSCI.1C00519"
}