Functional reconstitution of lost activity of chemically cross-linked or mutant moloney murine leukemia virus nucleocapsid proteins by trans-complementation.

Intermolecular crosslinking of the retroviral gag structural proteins, capsid (CA) and nucleocapsid (NC), by oxidation of cysteine thiols interferes with virus assembly and infectivity. PD156202 is a dithiobisbenzamide with broad antiviral activity against retroviruses. Treatment of cell free Moloney murine leukemia virus (MuLV) particles with PD156202 induced crosslinking of gag structural proteins and inhibited reverse transcription in mellitin permeabilized virions.

Evaluation of HIV-1 Tat induced neurotoxicity in rat cortical cell culture.

In a substantial number of cases, Human Immunodeficiency Virus type 1 (HIV-1) infection causes neuronal cell loss and leads to the development of AIDS associated dementia. Several studies have suggested that both host and viral factors contribute to neuronal loss. Here we studied the effect of HIV-1 Tat in primary rat neuronal cells as a model to understand mechanism of neuronal cell death.

Inhibition of the early phase of HIV replication by an isothiazolone, PD 161374.

A new class of substituted 2'-benzisothiazolone represented by PD 161374 was discovered with antiviral activity against retroviruses similar to previously described nucleocapsid inhibitor PD 159206 (DIBA-4). In T cell culture, the 50% inhibitory concentrations (EC(50)) of PD 161374 and PD 159206 were on average 2.5 microM (ranges of 1.

CCR5 has an expanded ligand-binding repertoire and is the primary receptor used by MCP-2 on activated T cells.

CCR5 is a chemokine receptor expressed by T cells and macrophages, which also functions as the principal coreceptor for macrophage (M)-tropic HIV-1 strains to enter the host cells. In this study, we aim to better understand the ligand-binding profiles of CCR5 and the chemokine-receptor usage on leukocyte cells. We found that MCP-2 could bind to CCR5 transfectants with high affinity and cross-compete effectively with RANTES, MIP-1alpha, and MIP-1beta.

Inhibitors of protein-RNA complexation that target the RNA: specific recognition of human immunodeficiency virus type 1 TAR RNA by small organic molecules.

TAR RNA represents an attractive target for the intervention of human immunodeficiency virus type 1 (HIV-1) replication by small molecules. We now describe three small molecule inhibitors of the HIV-1 Tat-TAR interaction that target the RNA, not the protein. The chemical structures and RNA binding characteristics of these inhibitors are unique for each molecule.