2. Academic Validation
  3. Synthesis and biological evaluation of novel peptidomimetic inhibitors of the coronavirus 3C-like protease

Synthesis and biological evaluation of novel peptidomimetic inhibitors of the coronavirus 3C-like protease

  • Eur J Med Chem. 2024 Feb 24:268:116263. doi: 10.1016/j.ejmech.2024.116263.
Franck Amblard 1,  Julia C LeCher 2,  Ramyani De 2,  Shaoman Zhou 2,  Peng Liu 2,  Shu Ling Goh 2,  Sijia Tao 2,  Dharmeshkumar Patel 2,  Jessica Downs-Bowen 2,  Keivan Zandi 2,  Huanchun Zhang 2,  Gitika Chaudhry 2,  Tamara McBrayer 2,  Michael Muczynski 3,  Abdullah Al-Homoudi 3,  Joseph Engel 3,  Shuiyun Lan 2,  Stefan G Sarafianos 2,  Ladislau C Kovari 3,  Raymond F Schinazi 4
Affiliations

Affiliations

  • 1 Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Children's Healthcare of Atlanta, Atlanta, GA, 30322, USA. Electronic address: [email protected].
  • 2 Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Children's Healthcare of Atlanta, Atlanta, GA, 30322, USA.
  • 3 Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
  • 4 Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Children's Healthcare of Atlanta, Atlanta, GA, 30322, USA. Electronic address: [email protected].
PMID: 38432056 DOI: 10.1016/j.ejmech.2024.116263
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and related variants, are responsible for the devastating coronavirus disease 2019 (COVID-19) pandemic. The SARS-CoV-2 main protease (Mpro) plays a central role in the replication of the virus and represents an attractive drug target. Herein, we report the discovery of novel SARS-CoV-2 Mpro covalent inhibitors, including highly effective compound NIP-22c which displays high potency against several key variants and clinically relevant nirmatrelvir Mpro E166V mutants.

Keywords

3CL(pro); Antivirals; HCoV-OC43; Main protease; Mpro; NIP-22c; Peptides; SARS-CoV-2.

Figures
Products