Models for how CADs May Block EBOV Entry.

(A) In the first model, the CADs (yellow star) interact directly with NPC1, but at a site distinct from the C loop of NPC1 (which binds GP_{19 kDa}). Binding to NPC1 inhibits a second function of NPC1 (i.e. in addition to its role in binding GP_{19 kDa}) that is critical for EBOV entry. (B) In the second model, the CADs intercalate into the LE/Lys membrane, indirectly inhibiting a second function of NPC1 that promotes EBOV entry. (C) In a final model, the CADs disrupt a target distinct from NPC1 that is critical for EBOV fusion with LE/Lys) and is regulated by NPC1. The target may be another LE/Lys protein (e.g. ASM) or a lipid of the LE/Lys membrane system. (See text for details.) Alternatively, the CADs may interfere with NPC1-dependent membrane trafficking [47], [50] such that the virus is never found in an NPC1-containing compartment. In all of the models, the yellow star denotes a CAD and red in each middle image denotes the target molecule.