Crimean-Congo hemorrhagic fever virus glycoprotein C (Gc)

The Crimean-Congo hemorrhagic fever virus (CCHFV) glycoprotein C (Gc) is a critical surface component of the viral envelope that functions as a class II viral fusion protein [Garrison et al., 2017, DOI: 10.1016/j.cell.2017.11.009]. CCHFV is a tick-borne virus in the Nairoviridae family that causes severe hemorrhagic fever in humans with mortality rates reaching up to 40% [WHO, 2022]. Gc is proteolytically cleaved from a precursor polyprotein encoded by the virus's M segment and exists as a heterodimer with the Gn protein on the virion surface [UniProt P21698]. During infection, the acidic environment of the host cell endosome triggers a dramatic conformational change in Gc, enabling the fusion of the viral and host membranes to release the viral genome into the cytoplasm [Garrison et al., 2017]. Because Gc is essential for viral entry and contains highly conserved epitopes, it is the primary target for the development of neutralizing monoclonal antibodies and vaccines [Fels et al., 2021, DOI: 10.1126/science.abd7502]. Experimental therapeutic candidates, such as the monoclonal antibody ADI-36121, work by binding to Gc and blocking these fusion-inducing structural rearrangements [Fels et al., 2021].

Other names

CCHFV GcGlycoprotein GcG2 proteinEnvelopment protein GcM segment polyprotein Gc subunit

Neutralization of viral infection by binding to conserved epitopes on the Gc protein, thereby preventing the pH-dependent conformational changes required for fusion between the viral envelope and the host endosomal membrane.