Pharmaceuticals, Volume 18, Issue 10
2025 October - 169 articles
Cover Story: Peptidomimetics incorporating a γ-lactam Gln derivative at the P1 site, originally developed as SARS-CoV-2 Mpro inhibitors, exhibited strong affinity for human cathepsin S (hCatS). In silico studies revealed that despite being solvent-exposed, the γ-lactam at P1 position might be involved in water-mediated hydrogen bonds. Molecular dynamics simulations suggested the presence of two predominant conformations, up and down, which differ in the γ-lactam orientation. Repurposing thousands of peptide-based SARS-CoV-2 Mpro inhibitors containing a γ-lactam at the P1 site, combined with new rational structure–activity relationship studies exploring the S1 pocket, could enable the identification of new potent and selective hCatS ligands. View this paper - Issues are regarded as officially published after their release is announced to the table of contents alert mailing list .
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