Photo by sharonmccutcheon from unsplash
Among the most important influenza virus targets is the RNA-dependent RNA polymerase acidic N-terminal (PAN) endonuclease, which is a critical component of the viral replication machinery. To inhibit the activity… Click to show full abstract
Among the most important influenza virus targets is the RNA-dependent RNA polymerase acidic N-terminal (PAN) endonuclease, which is a critical component of the viral replication machinery. To inhibit the activity of this metalloenzyme, small-molecule inhibitors employ metal-binding pharmacophores (MBPs) that coordinate to the dinuclear Mn2+ active site. In this study, several metal-binding isosteres (MBIs) were examined where the carboxylic acid moiety of a hydroxypyridinone MBP is replaced with other groups to modulate the physicochemical properties of the compound. MBIs were evaluated for their ability to inhibit PAN using a FRET-based enzymatic assay, and their mode of binding in PAN was determined using X-ray crystallography.
Journal Title: ACS Medicinal Chemistry Letters
Year Published: 2022
Link to full text (if available)
Share on Social Media: Sign Up to like & get
recommendations!