Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 541.8 Physical chemistry
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2016
• Mô tả vật lý: Size: p. 1899-1913 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260941
• Chủ đề: 1. 60 applied life sciences; 2. Inhibitors; 3. Macrocycles; 4. Noncovalent interactions; 5. Peptides and proteins; 6. Permeability

Tóm tắt

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. Herein we describe 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.