Target intelligence / Profile preview

Lassa virus glycoprotein complex (GPC) (LASV GPC)

Target
LASV GPC
Molecular classification
Viral envelope protein, Class I viral fusion protein, Glycoprotein
01

Overview

The Lassa virus glycoprotein complex (GPC) is the sole surface protein of the Lassa virus (LASV) and is essential for viral entry into host cells. It is synthesized as a precursor polyprotein that is cleaved by cellular proteases into two subunits: GP1, which mediates attachment to host receptors like alpha-dystroglycan and LAMP1, and GP2, which facilitates the fusion of the viral and host membranes (UniProt: P08669). As the primary target for the host immune response, GPC is the focus of vaccine development and therapeutic antibody discovery. Small molecule inhibitors like LHF-535 target the stable signal peptide (SSP)-GP2 interface to prevent the conformational changes required for fusion (Hastie et al., 2017). Neutralizing antibodies often target the quaternary epitopes of the GPC complex to block receptor binding or fusion (Robinson et al., 2016). Understanding the structural dynamics of GPC is critical for addressing the high genetic diversity of LASV across different geographical regions.

Other names
Lassa virus GPPre-glycoprotein polyprotein GPGP1/GP2 complexLassa virus envelope glycoprotein
02

Mechanism of action

Inhibition of viral entry by blocking receptor binding or preventing the pH-dependent conformational change required for membrane fusion.

03

Biological functions

Viral attachmentReceptor bindingMembrane fusionViral entry
04

Disease associations

Lassa feverViral hemorrhagic feverInfection
05

Safety considerations

High genetic diversity across LASV lineages (I-VII)Glycan shielding of epitopes hindering antibody accessPotential for viral escape mutations under selective pressure
06

Interacting drugs

LHF-535

3 more in the full profile.

07

Biomarkers

Neutralizing antibody titersGPC-specific IgG levelsGPC-specific IgM levelsViral RNA load

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