Lassa virus glycoprotein precursor (GPC)

The Lassa virus glycoprotein precursor (GPC) is a transmembrane viral fusion protein that is synthesized as a single ~76 kDa polypeptide and subsequently cleaved into three components—GP1, GP2, and a stable signal peptide (SSP)—by host signal peptidase and the subtilase SKI-1/S1P in the endoplasmic reticulum[5][2][3]. The mature GPC is unique among viral class I fusion proteins in that its signal peptide remains non-covalently associated with the trimeric spike complex, stabilizing the prefusion conformation and being essential for proper cleavage and trafficking[5][3][7]. The GP1 subunit mediates host cell recognition by binding to the carbohydrate matriglycan on the cell surface receptor α-dystroglycan, while GP2 drives the pH-dependent fusion of viral and cellular membranes[1][5][7]. The GPC is heavily N-glycosylated, with a dense glycan shield that helps the virus evade neutralizing antibodies[5][6]. Cleavage of the precursor is absolutely required for infectivity: only properly processed spikes are incorporated into virions, making GPC a validated and attractive antiviral drug and vaccine target[2][5][7]. GPC-based therapeutics aim to block receptor binding or membrane fusion and are currently in preclinical and clinical evaluation for Lassa fever, a severe hemorrhagic disease with high morbidity and mortality in endemic regions.

Other names

Lassa virus GP-CLassa virus GPCLASV GPCglycoprotein C precursorarenavirus glycoprotein precursor

Inhibition of membrane fusion; Blockade of receptor (α-dystroglycan/matriglycan) binding; Disruption of proteolytic cleavage or maturation; Immune neutralization by monoclonal antibodies