Ebolavirus glycoprotein - Niemann-Pick C1 receptor-binding site (EBOV GP-NPC1 RBS)

The Ebolavirus glycoprotein (GP) - Niemann-Pick C1 (NPC1) receptor-binding site is a critical molecular interface required for the entry of Ebolavirus into host cells (Carette et al., 2011, Nature). During the infection process, the virus is internalized into host endosomes where the viral GP is proteolytically processed by host cathepsins to remove the glycan cap and mucin-like domain, thereby exposing the receptor-binding site (RBS) on the GP1 subunit (Cote et al., 2011, Nature). This exposed RBS then binds specifically to the second luminal domain (Domain C) of the NPC1 protein, a host lysosomal membrane protein primarily responsible for cholesterol transport (Wang et al., 2016, Cell). This binding event is an absolute requirement for the subsequent GP2-mediated fusion of the viral envelope with the endosomal membrane, allowing the viral genome to enter the cytoplasm. Because NPC1 is a mandatory host factor for all known ebolaviruses, this binding site represents a high-priority target for the development of broad-spectrum antivirals (Miller et al., 2012, EMBO J). Therapeutic strategies include small molecules and monoclonal antibodies designed to block this protein-protein interaction, though care must be taken to avoid disrupting NPC1's native role in cellular cholesterol metabolism to prevent adverse effects similar to Niemann-Pick disease.

Other names

EBOV GP NPC1-binding domainNPC1-GP interfaceEbolavirus GP1 subunit receptor-binding siteNPC1 Domain C binding site

Inhibition of the physical interaction between the proteolytically primed Ebolavirus glycoprotein (GP1) and the host endosomal receptor Niemann-Pick C1 (NPC1), which prevents the fusion of the viral envelope with the host endosomal membrane and blocks viral entry into the cytoplasm.