We report the identification of three structurally diverse compounds – compound 4, GC376, and MAC-5576 – as inhibitors of the SARS-CoV-2 3CL protease. Structures of each of these compounds in complex with the protease revealed strategies for further development, as well as general principles for designing SARS-CoV-2 3CL protease inhibitors. These compounds may therefore serve as leads for the basis of building effective SARS-CoV-2 3CL protease inhibitors. The essential SARS-CoV-2 3CL protease is of interest as a drug target. Here, the authors identify three 3CL inhibitors and characterize them both in vitro and with a cell-based assay, and they also present the inhibitor-bound 3CL crystal structures, which may allow for the design of improved compounds.
【저자키워드】 SARS-CoV-2, Virology, Molecular medicine, X-ray crystallography, 【초록키워드】 Structure, protease, in vitro, inhibitors, protease inhibitors, drug target, inhibitor, 3CL, compounds, structures, crystal structures, leads, complex, Compound, these compounds, effective, identify, these compound, the SARS-CoV-2, 【제목키워드】 Protease inhibitor, 3CL,