Antiretroviral therapy for HIV-1 infection/AIDS has significantly extended the life expectancy of HIV-1-infected individuals and reduced HIV-1 transmission at very high rates. However, certain individuals who initially achieve viral suppression to undetectable levels may eventually suffer treatment failure mainly due to adverse effects and the emergence of drug-resistant HIV-1 variants. Here, we report GRL-142, a novel HIV-1 protease inhibitor containing an unprecedented 6-5-5-ring-fused crown-like tetrahydropyranofuran, which has extremely potent activity against all HIV-1 strains examined with IC50 values of attomolar-to-picomolar concentrations, virtually no effects on cellular growth, extremely high genetic barrier against the emergence of drug-resistant variants, and favorable intracellular and central nervous system penetration. GRL-142 forms optimum polar, van der Waals, and halogen bond interactions with HIV-1 protease and strongly blocks protease dimerization, demonstrating that combined multiple optimizing elements significantly enhance molecular and atomic interactions with a target protein and generate unprecedentedly potent and practically favorable agents.
Pubmed ID: 29039736 RIS Download
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A commercial antibody supplier and provider of various services.
View all literature mentionsGlobal nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsCommercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.
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View all literature mentionsSoftware designed to perform high-speed molecular dynamic simulations of biological systems on conventional commodity clusters, supercomputers and GPUs. This code uses novel parallel algorithms and numerical techniques to achieve high performance and accuracy on platforms with a large number of processors. It can be used with a single computer.
View all literature mentionsThe NIH Biowulf cluster is a GNU/Linux parallel processing system designed and built at the National Institutes of Health and managed by the Helix Systems Staff. The system is designed for large numbers of simultaneous jobs common in bioinformatics as well as large-scale distributed memory tasks such as molecular dynamics. Sponsor: This work was supported by the National Institutes of Health Intramural Research Program through the Center for Information Technology and the National Institute of Neurological Disorders and Stroke, and by the Internal National Institute of Standards and Technology Research Fund. Keywords: Software, Program, Processing, System, Simulatenous, Bioinformatics, Memory, Molecular, Dynamics,
View all literature mentionsA Python-based software suite for the automated determination of molecular structures using X-ray crystallography and other methods. Phenix includes programs for assessing data quality, experimental phasing, molecular replacement, model building, structure refinement, and validation. It also includes tools for reflection data and creating maps and models. Phenix can also be used for neutron crystallography. Tutorials and examples are available in the documentation tab.
View all literature mentionsPortal for Macromolecular X-Ray Crystallography to produce and support an integrated suite of programs that allows researchers to determine macromolecular structures by X-ray crystallography, and other biophysical techniques. Used in the education and training of scientists in experimental structural biology for determination and analysis of protein structure.
View all literature mentionsCollection of structural data of biological macromolecules. Database of information about 3D structures of large biological molecules, including proteins and nucleic acids. Users can perform queries on data and analyze and visualize results.
View all literature mentionsCell line COS-7 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)
View all literature mentionsCell line MT-4 is a Transformed cell line with a species of origin Homo sapiens
View all literature mentionsPortal for Macromolecular X-Ray Crystallography to produce and support an integrated suite of programs that allows researchers to determine macromolecular structures by X-ray crystallography, and other biophysical techniques. Used in the education and training of scientists in experimental structural biology for determination and analysis of protein structure.
View all literature mentionsSoftware designed to perform high-speed molecular dynamic simulations of biological systems on conventional commodity clusters, supercomputers and GPUs. This code uses novel parallel algorithms and numerical techniques to achieve high performance and accuracy on platforms with a large number of processors. It can be used with a single computer.
View all literature mentionsThe NIH Biowulf cluster is a GNU/Linux parallel processing system designed and built at the National Institutes of Health and managed by the Helix Systems Staff. The system is designed for large numbers of simultaneous jobs common in bioinformatics as well as large-scale distributed memory tasks such as molecular dynamics. Sponsor: This work was supported by the National Institutes of Health Intramural Research Program through the Center for Information Technology and the National Institute of Neurological Disorders and Stroke, and by the Internal National Institute of Standards and Technology Research Fund. Keywords: Software, Program, Processing, System, Simulatenous, Bioinformatics, Memory, Molecular, Dynamics,
View all literature mentionsA Python-based software suite for the automated determination of molecular structures using X-ray crystallography and other methods. Phenix includes programs for assessing data quality, experimental phasing, molecular replacement, model building, structure refinement, and validation. It also includes tools for reflection data and creating maps and models. Phenix can also be used for neutron crystallography. Tutorials and examples are available in the documentation tab.
View all literature mentionsCollection of structural data of biological macromolecules. Database of information about 3D structures of large biological molecules, including proteins and nucleic acids. Users can perform queries on data and analyze and visualize results.
View all literature mentionsCell line COS-7 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)
View all literature mentionsCell line MT-4 is a Transformed cell line with a species of origin Homo sapiens
View all literature mentionsA Python-based software suite for the automated determination of molecular structures using X-ray crystallography and other methods. Phenix includes programs for assessing data quality, experimental phasing, molecular replacement, model building, structure refinement, and validation. It also includes tools for reflection data and creating maps and models. Phenix can also be used for neutron crystallography. Tutorials and examples are available in the documentation tab.
View all literature mentionsPortal for Macromolecular X-Ray Crystallography to produce and support an integrated suite of programs that allows researchers to determine macromolecular structures by X-ray crystallography, and other biophysical techniques. Used in the education and training of scientists in experimental structural biology for determination and analysis of protein structure.
View all literature mentionsThe NIH Biowulf cluster is a GNU/Linux parallel processing system designed and built at the National Institutes of Health and managed by the Helix Systems Staff. The system is designed for large numbers of simultaneous jobs common in bioinformatics as well as large-scale distributed memory tasks such as molecular dynamics. Sponsor: This work was supported by the National Institutes of Health Intramural Research Program through the Center for Information Technology and the National Institute of Neurological Disorders and Stroke, and by the Internal National Institute of Standards and Technology Research Fund. Keywords: Software, Program, Processing, System, Simulatenous, Bioinformatics, Memory, Molecular, Dynamics,
View all literature mentionsSoftware designed to perform high-speed molecular dynamic simulations of biological systems on conventional commodity clusters, supercomputers and GPUs. This code uses novel parallel algorithms and numerical techniques to achieve high performance and accuracy on platforms with a large number of processors. It can be used with a single computer.
View all literature mentionsCell line COS-7 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)
View all literature mentionsCollection of structural data of biological macromolecules. Database of information about 3D structures of large biological molecules, including proteins and nucleic acids. Users can perform queries on data and analyze and visualize results.
View all literature mentionsCell line MT-4 is a Transformed cell line with a species of origin Homo sapiens
View all literature mentions