“…5,[10][11][12][13][14] Spurred by the recent SARS-CoV-2 pandemic, the N7-MTase nsp14 is an emerging target of great interest for inhibitor development, and over the past three years numerous groups worldwide have proposed original active compounds against this enzyme. 15-28 Most nsp14 inhibitors have been designed as SAM-derived compounds, 17,19,21,[23][24][25][26]28 but highthroughput screening of large libraries 18,20 or a structure-based docking approach on large libraries 27 have also lead to non-SAM-like inhibitors of nsp14. In the latest docking study, 27 the most potent inhibitors are low micromolar, much weaker than the most potent SAM-derived inhibitor, which is active in the subnanomolar range against SARS-CoV-2 nsp14.…”