Niemann-Pick C1 receptor–Zaire ebolavirus glycoprotein interaction

The Niemann-Pick C1 receptor (NPC1)–Zaire ebolavirus glycoprotein (GP) interaction is a critical protein-protein complex that facilitates Ebola virus entry into host cells during infection. Zaire ebolavirus GP, a trimeric class I viral fusion protein on the virion surface, mediates initial attachment via its GP1 subunit and subsequent membrane fusion via GP2, with NPC1 serving as the essential endosomal receptor that binds the primed GP after cathepsin cleavage removes the glycan cap and mucin-like domain. This interaction occurs in the late endosome, where NPC1's C-terminal domain engages a hydrophobic cavity on GP1, triggering conformational changes that drive fusion loop insertion into the host membrane and viral genome release. The GP trimer forms a chalice-like structure in its prefusion state, with GP1 forming the bowl that sequesters the receptor-binding site until proteolytic priming exposes it for NPC1 engagement. This process is central to filovirus pathogenesis, enabling immune evasion through heavy glycosylation and restricting neutralizing antibody access. Targeting this interaction holds therapeutic potential for blocking Ebola entry, though no approved drugs directly inhibit it; instead, it informs antibody and small-molecule strategies against viral fusion.

Other names

EBOV GP-NPC1 interactionZaire ebolavirus GP-NPC1 complex