Molecular Mechanism of HIV Entry Mediated by Chemokine Receptor CCR5

Information

  • Research Project
  • 8610241
  • ApplicationId
    8610241
  • Core Project Number
    R01AI100604
  • Full Project Number
    5R01AI100604-03
  • Serial Number
    100604
  • FOA Number
    PAR-11-145
  • Sub Project Id
  • Project Start Date
    2/15/2012 - 12 years ago
  • Project End Date
    1/31/2017 - 7 years ago
  • Program Officer Name
    SHARMA, OPENDRA K.
  • Budget Start Date
    2/1/2014 - 10 years ago
  • Budget End Date
    1/31/2015 - 9 years ago
  • Fiscal Year
    2014
  • Support Year
    03
  • Suffix
  • Award Notice Date
    1/14/2014 - 10 years ago

Molecular Mechanism of HIV Entry Mediated by Chemokine Receptor CCR5

DESCRIPTION (provided by applicant): This proposal Molecular Mechanism of HIV Entry Mediated by Chemokine Receptor CCR5 is focused on X-ray structure determination of complexes between chemokine receptor CCR5, an HIV entry co- receptor, and a variety of ligands including peptidomimetics. The ultimate goal is to use the experimentally determined structure to carry out drug discovery aimed at inhibiting HIV cell entry using structure-based drug design (SBDD) approaches. CCR5 is the primary co-receptor responsible for HIV transmission, while emergence of CXCR4-tropic (X4-tropic) viruses later in infection correlates with a more rapid CD4 decline and a faster progression to AIDS. As the predominant co-receptor for HIV entry, CCR5 has long been taken as one of the most important drug targets. Five CCR5 targeted drugs to date have been brought to clinical trial, but only one, Maraviroc, has been approved by FDA. Molecular details of how this drug as well as other CCR5 cell entry inhibitors works are not understood and will be a focus of the proposed study. The proposed structural studies will be carried out using methods and approaches of the Gene-to-Structure-Pipeline that was developed by the GPCR Network. The specific aims are: 1) Optimize the CCR5 construct design to generate large samples of highly purified and thermally stabilized CCR5 for biophysical and functional studies; 2) Design and synthesize chemical tools that can be used to stabilize CCR5 and to probe ligand-receptor interactions; 3) Develop an understanding of CCR5 ligand binding properties by determining the 3D structures of several complexes. It is expected that structural knowledge generated by our studies will lead to the development of new therapeutic strategies and help in stopping the growth of the HIV/AIDS epidemic in China and elsewhere in the world.

IC Name
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
  • Activity
    R01
  • Administering IC
    AI
  • Application Type
    5
  • Direct Cost Amount
    125000
  • Indirect Cost Amount
    10000
  • Total Cost
    135000
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    855
  • Ed Inst. Type
  • Funding ICs
    NIAID:135000\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    SHANGHAI INSTITUTE OF MATERIA MEDICA
  • Organization Department
  • Organization DUNS
    420985483
  • Organization City
    SHANGHAI
  • Organization State
  • Organization Country
    CHINA
  • Organization Zip Code
    201203
  • Organization District
    CHINA