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Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease.

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.

SUBMITTER: Damalanka VC

PROVIDER: S-EPMC5156532 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease.

Damalanka Vishnu C VC Kim Yunjeong Y Alliston Kevin R KR Weerawarna Pathum M PM Galasiti Kankanamalage Anushka C AC Lushington Gerald H GH Mehzabeen Nurjahan N Battaile Kevin P KP Lovell Scott S Chang Kyeong-Ok KO Groutas William C WC

Journal of medicinal chemistry 20160208 5

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 ...[more]

PMID: 26823007

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