Novel Central Nervous System (CNS)-Targeting Protease Inhibitors for Drug-Resistant HIV Infection and HIV-Associated CNS Complications
Year: 2019
Type: article
Abstract: There is currently no specific therapeutics for the HIV-1-related central nervous system (CNS) complications. Here we report that three newly designed CNS-targeting HIV-1 protease inhibitors (PIs), GRL-083-13, GRL-084-13, and GRL-087-13, which contain a P1-3,5- bis -fluorophenyl or P1- para -monofluorophenyl ring, and P2- bis -tetrahydrofuran ( bis -THF) or P2-tetrahydropyrano-tetrahydrofuran ( Tp -THF), with a sulfonamide isostere, are highly active against wild-type HIV-1 strains and primary clinical isolates (50% effective concentration [EC 50 ], 0.0002 to ∼0.003 μM), with minimal cytotoxicity.
DOI: 10.1128/aac.00466-19
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: National Center for Global Health and Medicine, Ministry of Education, Culture, Sports, Science and Technology, Ministry of Health, Labour and Welfare, National Institutes of Health, Japan Society for the Promotion of Science, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: Investigation of novel mechanism(s) regarding HIV-1 capsid protein degradation and uncoating, Development of Halogen-Containing Compounds Potent against Wild-type and Multidrug-Resistant HIV-1 Strains, Development of cross-virus drugs using norovirus as a model, DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS, Design & Synthesis of Nonpeptide Protease Inhibitors, Design & Synthesis of Nonpeptide Protease Inhibitors, Development of therapeutics for intractable infections using diverse natural products combined with stress-inductive biosynthesis and chemical modification, G9000252667
OpenAlex ID: W2940726674