Potent antiviral HIV-1 protease inhibitor combats highly drug resistant mutant PR20 [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 616.9792 Other diseases
• 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, 2019
• Mô tả vật lý: Size: p. 61-66 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261849
• Chủ đề: 1. 60 applied life sciences; 2. Antiretroviral inhibitor; 3. Drug resistance; 4. Hiv protease; 5. Structure-based design; 6. X-ray crystallography

Tóm tắt

Drug-resistance threatens effective treatment of HIV/AIDS. Clinical inhibitors, including darunavir (1), are ineffective for highly resistant protease mutant PR20, however, here antiviral compound 2 derived from 1 with fused tricyclic group at P2, extended amino-benzothiazole P2? ligand and two fluorine atoms on P1 shows 16-fold better inhibition of PR20 enzyme activity. Crystal structures of PR20 and wild-type PR complexes reveal how the extra groups of 2 counteract the expanded ligand-binding pocket, dynamic flaps, and faster dimer dissociation of PR20.