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New Thiazolidine-4-One Derivatives as SARS-CoV-2 Main Protease Inhibitors.
- Source :
-
Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2024 May 17; Vol. 17 (5). Date of Electronic Publication: 2024 May 17. - Publication Year :
- 2024
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Abstract
- It has been more than four years since the first report of SARS-CoV-2, and humankind has experienced a pandemic with an unprecedented impact. Moreover, the new variants have made the situation even worse. Among viral enzymes, the SARS-CoV-2 main protease (M <superscript>pro</superscript> ) has been deemed a promising drug target vs. COVID-19. Indeed, M <superscript>pro</superscript> is a pivotal enzyme for viral replication, and it is highly conserved within coronaviruses. It showed a high extent of conservation of the protease residues essential to the enzymatic activity, emphasizing its potential as a drug target to develop wide-spectrum antiviral agents effective not only vs. SARS-CoV-2 variants but also against other coronaviruses. Even though the FDA-approved drug nirmatrelvir, a M <superscript>pro</superscript> inhibitor, has boosted the antiviral therapy for the treatment of COVID-19, the drug shows several drawbacks that hinder its clinical application. Herein, we report the synthesis of new thiazolidine-4-one derivatives endowed with inhibitory potencies in the micromolar range against SARS-CoV-2 M <superscript>pro</superscript> . In silico studies shed light on the key structural requirements responsible for binding to highly conserved enzymatic residues, showing that the thiazolidinone core acts as a mimetic of the Gln amino acid of the natural substrate and the central role of the nitro-substituted aromatic portion in establishing π-π stacking interactions with the catalytic His-41 residue.
Details
- Language :
- English
- ISSN :
- 1424-8247
- Volume :
- 17
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Pharmaceuticals (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 38794220
- Full Text :
- https://doi.org/10.3390/ph17050650