2. Academic Validation
  3. Biochemical and genetic characterizations of a novel human immunodeficiency virus type 1 inhibitor that blocks gp120-CD4 interactions

Biochemical and genetic characterizations of a novel human immunodeficiency virus type 1 inhibitor that blocks gp120-CD4 interactions

  • J Virol. 2003 Oct;77(19):10528-36. doi: 10.1128/jvi.77.19.10528-10536.2003.
Qi Guo 1,  Hsu-Tso Ho,  Ira Dicker,  Li Fan,  Nannan Zhou,  Jacques Friborg,  Tao Wang,  Brian V McAuliffe,  Hwei-Gene Heidi Wang,  Ronald E Rose,  Hua Fang,  Helen T Scarnati,  David R Langley,  Nicholas A Meanwell,  Ralph Abraham,  Richard J Colonno,  Pin-Fang Lin
Affiliations

Affiliation

  • 1 Department of Virology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA.
PMID: 12970437 DOI: 10.1128/jvi.77.19.10528-10536.2003
Abstract

BMS-378806 is a recently discovered small-molecule human immunodeficiency virus type 1 (HIV-1) attachment inhibitor with good Antiviral activity and pharmacokinetic properties. Here, we demonstrate that the compound targets viral entry by inhibiting the binding of the HIV-1 envelope gp120 protein to cellular CD4 receptors via a specific and competitive mechanism. BMS-378806 binds directly to gp120 at a stoichiometry of approximately 1:1, with a binding affinity similar to that of soluble CD4. The potential BMS-378806 target site was localized to a specific region within the CD4 binding pocket of gp120 by using HIV-1 gp120 variants carrying either compound-selected resistant substitutions or gp120-CD4 contact site mutations. Mapping of resistance substitutions to the HIV-1 envelope, and the lack of compound activity against a CD4-independent viral Infection confirm the gp120-CD4 interactions as the target in infected cells. BMS-378806 therefore serves as a prototype for this new class of antiretroviral agents and validates gp120 as a viable target for small-molecule inhibitors.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-14134
    98.94%, HIV抑制剂
    HIV
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