Submission Details

Design Rationale:

We performed a fragment-guided approach using ZINCPharmer, where the 17 active fragments from the XChem Mpro screen were used as the pharmacophore queries to search the ZINC databases of natural compounds and natural derivatives. This search yielded 134 hits that were then subjected to multiple rounds of in silico analyses, including blind and focused docking against the 3D structure of the main protease. We scrutinized the poses, scores, and protein-ligand interactions and selected a number of hits. The scaffolds of our seven hits were structurally distinct from the known inhibitor scaffolds, thus indicating scaffold novelty. You can find our manuscript on this work at: https://www.mdpi.com/900426