Recent X-ray crystallographic determination of the HIV-1 envelope glycoprotein gp41 core structure opened up a new avenue to discover antiviral agents for chemotherapy of HIV-1 infection and AIDS. We have undertaken a systematic study to search for anti-HIV-1 lead compounds targeted to gp41. Using molecular docking techniques to screen a database of 20 000 organic molecules, we found 16 compounds with the best fit for docking into the hydrophobic cavity within the gp41 core and with maximum possible interactions with the target site. Further testing of these compounds by an enzyme-linked immunosorbent assay and virus inhibition assays discerned two compounds (ADS-J1 and ADS-J2) having inhibitory activity at micromolar concentrations on the formation of the gp41 core structure and on HIV-1 infection. These two compounds will be used as leads to design more effective HIV-1 inhibitors targeted to the HIV-1 gp41 core structure.

Additional causes of this common immune deficiency syndrome remain to be determined.

Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired antibody responses, recurrent infections, inflammatory, autoimmune and malignancyrelated conditions. We evaluated the relationship between memory B cell phenotype, sex, age at diagnosis, immunologic and clinical conditions in 105 CVID subjects from one medical center. Reduced numbers of switched memory B cells (cutoff ≤0.55% of B cells) were an independent risk factor of granulomas, autoimmune diseases and splenomegaly (p<0.001). Not previously noted, CVID females had significantly more switched memory cells (p=0.007) than males. Splenectomized subjects did not have fewer IgM memory B cells and these numbers were not related to the development of lung disease, as previously proposed. Lower baseline serum IgG was an independent predictor of pneumonia (p=0.007) and severe infections (p=0.001). We conclude that outcomes in CVID depend on an interplay of factors including sex, numbers of switched memory B cells, and baseline serum IgG and IgA levels.

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Background-Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia, reduced numbers of peripheral blood isotype-switched memory B cells, and loss of plasma cells.