2. Academic Validation
  3. Synthesis and antiviral evaluation of novel peptidomimetics as norovirus protease inhibitors

Synthesis and antiviral evaluation of novel peptidomimetics as norovirus protease inhibitors

  • Bioorg Med Chem Lett. 2018 Jul 1;28(12):2165-2170. doi: 10.1016/j.bmcl.2018.05.012.
Franck Amblard 1,  Shaoman Zhou 1,  Peng Liu 1,  Jack Yoon 1,  Bryan Cox 1,  Kendall Muzzarelli 2,  Benjamin D Kuiper 2,  Ladislau C Kovari 2,  Raymond F Schinazi 3
Affiliations

Affiliations

  • 1 Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • 2 Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
  • 3 Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: rschina@emory.edu.
PMID: 29779977 DOI: 10.1016/j.bmcl.2018.05.012
Abstract

A series of tripeptidyl transition state inhibitors with new P1 and warhead moieties were synthesized and evaluated in a GI-1 norovirus replicon system and against GII-4 and GI-1 norovirus proteases. Compound 19, containing a 6-membered ring at the P1 position and a reactive aldehyde warhead exhibited sub-micromolar replicon inhibition. Retaining the same peptidyl scaffold, several reactive warheads were tested for protease inhibition and norovirus replicon inhibition. Of the six that were synthesized and tested, compounds 42, 43, and 45 potently inhibited the protease in biochemical assay and GI-1 norovirus replicon in the nanomolar range.

Keywords

Antiviral; Norovirus; Peptide; Protease inhibitor.

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