Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56lck

Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56lck.

With current anti-HIV treatments targeting only 4 of the 15 HIV proteins, many potential viral vulnerabilities remain unexploited. We report small-molecule inhibitors of the HIV-1 protein Nef. In addition to expanding the anti-HIV arsenal, small-molecule inhibitors against untargeted HIV proteins could be used to dissect key events in the HIV lifecycle. Numerous incompletely characterized inter...

Piperidinylethanamine Analogs as Anti-HIV-1 Inhibitors

Interactions of HIV-1 NEF with cellular signal transducing proteins.

Nef is a 27 - 34 kD myristoylated protein unique to primate lentiviruses. A functional Nef gene is important for development of high viremia and simian AIDS in SIV infected rhesus macaques (1). In a transgenic mouse model expression of Nef protein alone when expressed under a CD4-promoter is sufficient to cause an AIDS like disease (2). A critical role for Nef in development of AIDS in humans i...

HIV-1 Nef disrupts the podocyte actin cytoskeleton by interacting with diaphanous interacting protein.

The ability of the human immunodeficiency virus, type 1 (HIV-1) protein Nef to induce cytoskeleton changes in infected host cells is a key event in viral replication. In renal podocytes, we found that Nef induced loss of stress fibers and increased lamellipodia, pathological changes leading to proteinuria in HIV-associated nephropathy. These morphological changes were mediated by Nef-induced Ra...

Library versus library recognition and inhibition of the HIV-1 Nef allelome.

Rapid evolution of drug-resistant viruses renders essentially all small-molecule antiviral treatments ineffective. We demonstrate an in vitro library versus library approach to identify small molecules targeting a broad spectrum of HIV-1 Nef protein variants. The technique could provide more effective antiviral therapies. First, a library of clinically derived Nef allelic variants, termed an al...