Characterization of two novel FANCG mutations in Indian Fanconi anemia patients.

FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. We have studied three patients clinically diagnosed as FA. All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c.1471_1473delAAAinsG. We have for the first time modeled FANCG protein with fold based template search using pGenthreader which revealed sequence fold identical to super helical TPR domain of O linked GLCNAC transferase and have studied the impact of mutations on the function and structure of FANCG. All three mutations are potential pathogenic molecular changes which can affect FANCG interactions required for FA pathway, homologous recombination repairs and unhooking step of the ICL repair process.

HbAHP-25, an In-Silico Designed Peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor.

Human Immunodeficiency Virus (HIV-1) poses a serious threat to the developing world and sexual transmission continues to be the major source of new infections. Therefore, the development of molecules, which prevent new HIV-1 infections, is highly warranted. In the present study, a panel of human hemoglobin (Hb)-α subunit derived peptides and their analogues, with an ability to bind gp120, were designed in-silico and their anti-HIV-1 activity was evaluated. Of these peptides, HbAHP-25, an analogue of Hb-α derived peptide, demonstrated significant anti-HIV-1 activity. HbAHP-25 was found to be active against CCR5-tropic HIV-1 strains (ADA5 and BaL) and CXCR4-tropic HIV-1 strains (IIIB and NL4-3). Surface plasmon resonance (SPR) and ELISA revealed direct interaction between HbAHP-25 and HIV-1 envelope protein, gp120. The peptide prevented binding of CD4 to gp120 and blocked subsequent steps leading to entry and/or fusion or both. Anti-HIV activity of HbAHP-25 appeared to be specific as it failed to inhibit the entry of HIV-1 pseudotyped virus (HIV-1 VSV). Further, HbAHP-25 was found to be non-cytotoxic to TZM-bl cells, VK2/E6E7 cells, CEM-GFP cells and PBMCs, even at higher concentrations. Moreover, HbAHP-25 retained its anti-HIV activity in presence of seminal plasma and vaginal fluid. In brief, the study identified HbAHP-25, a novel anti-HIV peptide, which directly interacts with gp120 and thus has a potential to inhibit early stages of HIV-1 infection.