Home
Resources
Publications
A Broad HIV-1 Inhibitor Blocks Envelope Glycoprotein Transitions Critical for Entry

A Broad HIV-1 Inhibitor Blocks Envelope Glycoprotein Transitions Critical for Entry

Alon Herschhorn, Christopher Gu, Nicole Espy, Jonathan Richard, Andrés Finzi, Joseph G Sodroski

Nat Chem Biol. 2014 Oct;10(10):845-52.

PMID: 25174000

Abstract:

Binding to the primary receptor, CD4, triggers conformational changes in the metastable HIV-1 envelope glycoprotein (Env) trimer ((gp120-gp41)3) that are important for virus entry into host cells. These changes include an 'opening' of the trimer, creation of a binding site for the CCR5 co-receptor and formation and/or exposure of a gp41 coiled coil. Here we identify a new compound, 18A (1), that specifically inhibits the entry of a wide range of HIV-1 isolates. 18A does not interfere with CD4 or CCR5 binding, but it inhibits the CD4-induced disruption of quaternary structures at the trimer apex and the exposure of the gp41 HR1 coiled coil. Analysis of HIV-1 variants with increased or reduced sensitivity to 18A suggests that the inhibitor can distinguish distinct conformational states of gp120 in the unliganded Env trimer. The broad-range activity and observed hypersensitivity of resistant mutants to antibody neutralization support further investigation of 18A.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP331261508	HIV inhibitor 18A		331261-50-8	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: