Hong Lu

US Patent:

20060287319, Dec 21, 2006

Filed:

Jun 6, 2006

Appl. No.:

11/448439

Inventors:

Shibo Jiang - Fresh Meadows NY, US
Asim Debnath - Fort Lee NJ, US
Hong Lu - Bayside NY, US

International Classification:

A61K 31/53
A61K 31/501
A61K 31/497
A61K 31/496
A61K 31/4439
A61K 31/427

US Classification:

514241000, 514252130, 514255050, 514252020, 514252050, 514369000, 514253090, 514341000, 514342000

Abstract:

A group of compounds that inhibit HIV replication by blocking HIV entry was identified. One representative compound, designated NB-206, and its analogs inhibited HIV replication (p24 production) with ICvalues at nanomolar levels. It was proved that NB-206 and its analogs are HIV entry inhibitors by targeting the HIV gp41 since: 1) they inhibited HIV-mediated cell fusion; 2) they inhibited HIV replication only when they were added to the cells less than one hour after virus addition; 3) they blocked the formation of the gp41 core that is detected by sandwich enzyme linked immunosorbent assay (ELISA) using a conformation-specific MAb NC-1; and 4) they inhibited the formation of the gp41 six-helix bundle revealed by fluorescence native-polyacrylamide gel electrophoresis (FN-PAGE). These results suggested that NB-206 and its analogs may interact with the hydrophobic cavity and block the formation of the fusion-active gp41 coiled coil domain, resulting in inhibition of HIV-1 mediated membrane fusion and virus entry.