Session: Posters:

SARS-CoV-2 main protease (M^pro) plays an essential role in the viral replication and transcription of the novel coronavirus. Hence, it has been identified as a validated drug target against COVID-19. We have rationally designed 141 novel peptidomimetic inhibitors with a variety of electrophilic warheads expected to alkylate the active site nucleophilic cysteinyl sulfur atom of SARS-CoV-2 M^pro. We obtained preliminary results from molecular docking with Schrödinger’s Maestro of these 141 newly proposed, novel peptidomimetic inhibitors into the known crystal structure of SARS-CoV-2 M^pro (PDB ID: 6LU7). The energetic scores for the docked poses were compared in reference to both the co-crystalized ligand of 6LU7 (N3, a known wide-spectrum Michael acceptor 3C protease inhibitor with k_obs/[I] 4,700-47,000 M^-1s^-1) as well as a recently tested and published peptidomimetic α-ketoamide. Our in silico approach has led to 15 novel compounds that performed better than the published reference compounds and are currently being synthesized and developed.

Ozlem Dogan Ekici

Appearances