Back to the future: Advances in development of broad-spectrum capsid-binding inhibitors of enteroviruses

  • Eur J Med Chem. 2019 Sep 15:178:606-622. doi: 10.1016/j.ejmech.2019.06.008.
Anna Egorova  1 ,  Sean Ekins  2 ,  Michaela Schmidtke  3 ,  Vadim Makarov  4
Affiliations
  • 1. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky prospekt 33-2, Moscow, 119071, Russia.
  • 2. Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, NC27606, USA.
  • 3. Jena University Hospital, Department of Medical Microbiology, Section Experimental Virology, Hans-Knöll-Str. 2, 07745, Jena, Germany.
  • 4. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky prospekt 33-2, Moscow, 119071, Russia. Electronic address: [email protected].
PMID: 31226653 DOI: 10.1016/j.ejmech.2019.06.008
Abstract

The hydrophobic pocket within viral capsid protein 1 is a target to combat the rhino- and enteroviruses (RV and EV) using small molecules. The highly conserved Amino acids lining this pocket enable the development of antivirals with broad-spectrum of activity against numerous RVs and EVs. Inhibitor binding blocks: the attachment of the virion to the host cell membrane, viral uncoating, and/or production of infectious virus particles. Syntheses and biological studies of the most well-known antipicornaviral capsid Binders have been reviewed and we propose next steps in this research.

Keywords
Antivirals; Common cold; Drug design/discovery; Enterovirus; Pleconaril; Rhinovirus.