Proposed model of the mechanism of action of BFFI. The fusion process of an R5 virus with the host cell is depicted in Figure A. HIV entry begins with an initial contact of between the viral envelope protein gp120 and the cell surface receptor CD4, followed by gp120 binding to the co-receptor CCR5. This leads to conformational changes in gp120 and the insertion of HIV gp41 N-terminal fusion peptides into the cell membrane. The C-helical heptad repeats (C-HR) and N-helical heptad repeats (N-HR) form a six helix bundle bringing viral envelope and cell membrane in close proximity and resulting in fusion. B. During an R5 HIV infection in the presence of BFFI, binding of BFFI to CCR5 markedly enhances the cell surface concentration of FI and possibility of interference with HIV gp41. C. During an X4 HIV infection in cells that express both CCR5 and CXCR4 in the presence of BFFI, the same result is obtained. If the X4 virus is able to enter the fusion stage by binding to nearby CD4 and CXCR4, the FIs within BFFI can effectively inhibit the six-helix bundle formation. D. If cells are pre-coated with CCR5mAb, BFFI is no longer able to bind to CCR5 and will not be effective at blocking the X4 HIV fusion.