2. Academic Validation
  3. The Basicity Makes the Difference: Improved Canavanine-Derived Inhibitors of the Proprotein Convertase Furin

The Basicity Makes the Difference: Improved Canavanine-Derived Inhibitors of the Proprotein Convertase Furin

  • ACS Med Chem Lett. 2021 Feb 9;12(3):426-432. doi: 10.1021/acsmedchemlett.0c00651.
Thuy Van Lam van 1,  Miriam Ruth Heindl 2,  Christine Schlutt 1,  Eva Böttcher-Friebertshäuser 2,  Ralf Bartenschlager 3,  Gerhard Klebe 1,  Hans Brandstetter 4,  Sven O Dahms 1 4,  Torsten Steinmetzer 1
Affiliations

Affiliations

  • 1 Institute of Pharmaceutical Chemistry, Philipps University, Marbacher Weg 6, 35032 Marburg, Germany.
  • 2 Institute of Virology, Philipps University, Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
  • 3 Department of Infectious Diseases, Molecular Virology, Heidelberg University and German Center for Infection Research, Heidelberg Partner Site, Im Neuenheimer Feld 344, 69120 Heidelberg, Germany.
  • 4 Department of Biosciences, University of Salzburg, Billrothstrasse 11, 5020 Salzburg, Austria.
PMID: 33732412 DOI: 10.1021/acsmedchemlett.0c00651
Abstract

Furin activates numerous viral glycoproteins, and its inhibition prevents virus replication and spread. Through the replacement of arginine by the less basic canavanine, new inhibitors targeting Furin in the trans-Golgi network were developed. These inhibitors exert potent Antiviral activity in Cell Culture with much lower toxicity than arginine-derived analogues, most likely due to their reduced protonation in the blood circulation. Thus, despite its important physiological functions, Furin might be a suitable Antiviral drug target.

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