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Alternative In Vitro Methods for the Determination of Viral Capsid Structural Integrity
Published on: November 16, 2017
Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease
Vishnu C Damalanka1, Yunjeong Kim2, Kevin R Alliston1
1Department of Chemistry, Wichita State University , Wichita, Kansas 67260, United States.
Abstract:
Human noroviruses are the primary causative agents of acute gastroenteritis and a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or prophylaxis of norovirus infections. Norovirus 3CL protease plays a vital role in viral replication by generating structural and nonstructural proteins via the cleavage of the viral polyprotein. Thus, molecules that inhibit the viral protease may have potential therapeutic value. We describe herein the structure-based design, synthesis, and in vitro and cell-based evaluation of the first class of oxadiazole-based, permeable macrocyclic inhibitors of norovirus 3CL protease.
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