Background: Reovirus type 3 Dearing strain (ReoT3D) has an inherent propensity to preferentially infect and destroy cancer cells. The oncolytic activity of ReoT3D as a single agent has been demonstrated in vitro and in vivo against various cancers, including colon, pancreatic, ovarian and breast cancers. Its human safety and potential efficacy are currently being investigated in early clinical trials. In this study, we investigated the in vitro combination effects of ReoT3D and chemotherapeutic agents against human non-small cell lung cancer (NSCLC).

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The interaction between human immunodeficiency virus type 1 (HIV-1) gp120 and the CD4 receptor is highly specific and involves relatively small contact surfaces on both proteins according to crystal structure analysis. This molecularly conserved interaction presents an excellent opportunity for antiviral targeting. Here we report a group of pentavalent antimony-containing small molecule compounds, NSC 13778 (molecular weight, 319) and its analogs, which exert a potent anti-HIV activity. These compounds block the entry of X4-, R5-, and X4/R5-tropic HIV-1 strains into CD4؉ cells but show little or no activity in CD4-negative cells or against vesicular stomatitis virus-G pseudotyped virions. The compounds compete with gp120 for binding to CD4: either immobilized on a solid phase (soluble CD4) or on the T-cell surface (native CD4 receptor) as determined by a competitive gp120 capture enzyme-linked immunosorbent assay or flow cytometry. NSC 13778 binds to an N-terminal two-domain CD4 protein, D1/D2 CD4, immobilized on a surface plasmon resonance sensor chip, and dose dependently reduces the emission intensity of intrinsic tryptophan fluorescence of D1/D2 CD4, which contains two of the three tryptophan residues in the gp120-binding domain. Furthermore, T cells incubated with the compounds alone show decreased reactivity to anti-CD4 monoclonal antibodies known to recognize the gp120-binding site. In contrast to gp120-binders that inhibit gp120-CD4 interaction by binding to gp120, these compounds appear to disrupt gp120-CD4 contact by targeting the specific gp120-binding domain of CD4. NSC 13778 may represent a prototype of a new class of HIV-1 entry inhibitors that can break into the gp120-CD4 interface and mask the gp120-binding site on the CD4 molecules, effectively repelling incoming virions.Human immunodeficiency virus type 1 (HIV-1) infection of target cells begins with the attachment of virions to its primary receptor, the cell surface CD4 (16,38). This first step of viral entry into the host is mediated by a highly specific and structurally regulated interaction between the viral envelope glycoprotein gp120 and CD4 molecules. The HIV virion surface is coated with viral envelope spikes, which are composed of trimeric heterodimers of the exterior gp120 and transmembrane gp41 glycoprotein (41). The binding of gp120 to CD4 triggers a cascade of conformational changes in the viral envelope protein: first, the exposure of gp120 coreceptor (CXCR4 or CCR5)-binding site and the subsequent engagement of the coreceptors (41), followed by the formation of gp41 prehairpin intermediates and "fusion-active" trimer-of-hairpins required for the final step of virion entry (10, 45). Thus, of the three distinct sequential events of HIV entry process (i.e., virion attachment to CD4, coreceptor binding, and virion-cell membrane fusion), the binding of gp120 and CD4 molecules clearly dictates the subsequent key steps of viral invasion into the host cells.The gp120 glycoprotein binds to the most N-terminal domain 1 (D1) of CD4, centeri...

In pediatric AIDS, the protective effect of CCR5 wt/Delta 32 is more pronounced in early years of infection and appears to be abrogated by the SDF1-3'A genotype.

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