Marburg virus glycoprotein GP1 NPC1 receptor-binding site (MARV GP1 RBS)

The Marburg virus glycoprotein GP1 NPC1 receptor-binding site is a critical functional domain on the surface of the Marburg virus (MARV) responsible for mediating viral entry into host cells. MARV GP is synthesized as a precursor (GP0) that is cleaved into GP1 and GP2 subunits; GP1 contains the receptor-binding site (RBS) which remains sequestered by a glycan cap and mucin-like domain until the virus is internalized into host endosomes. Within the endosome, host proteases such as cathepsin B and L cleave the glycan cap to expose the RBS, allowing it to bind specifically to the C-domain of the host intracellular receptor Niemann-Pick C1 (NPC1). This binding event is the essential trigger for GP2-mediated fusion between the viral and endosomal membranes. Because this site is highly conserved across Marburg virus strains and is indispensable for infection, it serves as a primary target for neutralizing monoclonal antibodies, such as MR191, which mimic the NPC1 receptor binding to block viral escape from the endosome. Therapeutic strategies targeting this site aim to prevent the initiation of the viral replication cycle, offering a potent mechanism for treating Marburg virus disease.

Other names

Marburg virus GP1 receptor-binding domainMARV GP NPC1-binding siteMarburg virus glycoprotein receptor-binding siteMARV GP1-NPC1 interface

Neutralization of viral infectivity by blocking the interaction between the viral glycoprotein and the host intracellular receptor Niemann-Pick C1 (NPC1), thereby preventing membrane fusion and viral genome release into the cytoplasm.