Please wait, while we are loading the content...
Please wait, while we are loading the content...
| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Schleif, William A. Ellis, Joan D. Zhuang, Linghang Chen, I-wu Young, Steven D. Jolly, Samson M. Egbertson, Melissa S. Jin, Lixia Grobler, Jay Xu, Wei Vacca, Joseph P. Wai, John S. Embrey, Mark Lin, Jiunn H. Danovich, Robert Hazuda, Daria J. Espeseth, Amy S. Stillmock, Kara A. Huff, Joel R. Felock, Peter J. Miller, Michael D. Guare, James P. Gomez, Robert P. Emini, Emilio Kassahun, Kelem Pearson, Paul G. Wong, Bradley K. Fisher, Thorsten E. Holloway, M. Katharine Summa, Vincenzo Anthony, Neville J. Witmer, Marc V. Cortese, Riccardo |
| Description | Author Affiliation: Hazuda DJ ( Department of Biological Chemistry, Merck Research Laboratories, P.O. Box 4, West Point, PA 19486, USA. daria_hazuda@merck.com); |
| Abstract | The increasing incidence of resistance to current HIV-1 therapy underscores the need to develop antiretroviral agents with new mechanisms of action. Integrase, one of three viral enzymes essential for HIV-1 replication, presents an important yet unexploited opportunity for drug development. We describe here the identification and characterization of L-870,810, a small-molecule inhibitor of HIV-1 integrase with potent antiviral activity in cell culture and good pharmacokinetic properties. L-870,810 is an inhibitor with an 8-hydroxy-(1,6)-naphthyridine-7-carboxamide pharmacophore. The compound inhibits HIV-1 integrase-mediated strand transfer, and its antiviral activity in vitro is a direct consequence of this ascribed effect on integration. L-870,810 is mechanistically identical to previously described inhibitors from the diketo acid series; however, viruses selected for resistance to L-870,810 contain mutations (integrase residues 72, 121, and 125) that uniquely confer resistance to the naphthyridine. Conversely, mutations associated with resistance to the diketo acid do not engender naphthyridine resistance. Importantly, the mutations associated with resistance to each of these inhibitors map to distinct regions within the integrase active site. Therefore, we propose a model of the two inhibitors that is consistent with this observation and suggests specific interactions with discrete binding sites for each ligand. These studies provide a structural basis and rationale for developing integrase inhibitors with the potential for unique and nonoverlapping resistance profiles. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 31 |
| Volume Number | 101 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2004-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | HIV Infections Drug Therapy HIV Integrase Inhibitors Pharmacology HIV-1 Drug Effects Naphthyridines Animals Cells, Cultured Drug Resistance, Multiple Drug Resistance, Viral HIV Integrase Genetics Metabolism Chemistry Enzymology HIV-2 Macaca Mulatta Mutagenesis, Site-Directed Simian Immunodeficiency Virus T-Lymphocytes Cytology Virology Virus Integration Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
National Digital Library of India (NDLI) is a virtual repository of learning resources which is not just a repository with search/browse facilities but provides a host of services for the learner community. It is sponsored and mentored by Ministry of Education, Government of India, through its National Mission on Education through Information and Communication Technology (NMEICT). Filtered and federated searching is employed to facilitate focused searching so that learners can find the right resource with least effort and in minimum time. NDLI provides user group-specific services such as Examination Preparatory for School and College students and job aspirants. Services for Researchers and general learners are also provided. NDLI is designed to hold content of any language and provides interface support for 10 most widely used Indian languages. It is built to provide support for all academic levels including researchers and life-long learners, all disciplines, all popular forms of access devices and differently-abled learners. It is designed to enable people to learn and prepare from best practices from all over the world and to facilitate researchers to perform inter-linked exploration from multiple sources. It is developed, operated and maintained from Indian Institute of Technology Kharagpur.
Learn more about this project from here.
NDLI is a conglomeration of freely available or institutionally contributed or donated or publisher managed contents. Almost all these contents are hosted and accessed from respective sources. The responsibility for authenticity, relevance, completeness, accuracy, reliability and suitability of these contents rests with the respective organization and NDLI has no responsibility or liability for these. Every effort is made to keep the NDLI portal up and running smoothly unless there are some unavoidable technical issues.
Ministry of Education, through its National Mission on Education through Information and Communication Technology (NMEICT), has sponsored and funded the National Digital Library of India (NDLI) project.
| Sl. | Authority | Responsibilities | Communication Details |
|---|---|---|---|
| 1 | Ministry of Education (GoI), Department of Higher Education |
Sanctioning Authority | https://www.education.gov.in/ict-initiatives |
| 2 | Indian Institute of Technology Kharagpur | Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project | https://www.iitkgp.ac.in |
| 3 | National Digital Library of India Office, Indian Institute of Technology Kharagpur | The administrative and infrastructural headquarters of the project | Dr. B. Sutradhar bsutra@ndl.gov.in |
| 4 | Project PI / Joint PI | Principal Investigator and Joint Principal Investigators of the project |
Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon |
| 5 | Website/Portal (Helpdesk) | Queries regarding NDLI and its services | support@ndl.gov.in |
| 6 | Contents and Copyright Issues | Queries related to content curation and copyright issues | content@ndl.gov.in |
| 7 | National Digital Library of India Club (NDLI Club) | Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach | clubsupport@ndl.gov.in |
| 8 | Digital Preservation Centre (DPC) | Assistance with digitizing and archiving copyright-free printed books | dpc@ndl.gov.in |
| 9 | IDR Setup or Support | Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops | idr@ndl.gov.in |
|
Loading...
|