Crimean-Congo haemorrhagic fever virus glycoprotein precursor (CCHFV GPC)

The Crimean-Congo haemorrhagic fever virus (CCHFV) glycoprotein precursor is a large polyprotein encoded by the M segment of the viral genome (UniProt P23510). It undergoes extensive proteolytic processing by host cell proteases, such as SKI-1/S1P and furin, to generate the mature structural glycoproteins Gn and Gc, as well as several non-structural proteins including GP160, GP85, GP38, and NSm (Sanchez et al., 2002, J. Virol.). Gn and Gc are essential for the viral life cycle, mediating attachment to host cell receptors and facilitating pH-dependent membrane fusion within the endosome to release the viral genome into the cytoplasm (Garrison et al., 2007, J. Virol.). As the primary surface-exposed components of the virion, these glycoproteins are the principal targets for neutralizing antibodies and are the focus of vaccine development efforts (Fels et al., 2021, Cell). Therapeutic strategies targeting the glycoprotein precursor include monoclonal antibodies like ADI-36121 that block viral entry and DNA or viral-vectored vaccines designed to elicit a protective immune response (Zivcec et al., 2016, J. Infect. Dis.). Additionally, inhibitors of the host proteases required for precursor processing, such as the SKI-1/S1P inhibitor PF-429242, have shown potential in reducing viral titers in experimental models (Vincent et al., 2003, J. Virol.).

Other names

M segment polyproteinCCHFV glycoproteinGn and Gc glycoproteinsPre-GnPre-GcGP160GP85GP38NSm

Neutralization of viral entry by blocking receptor binding or inhibiting pH-dependent membrane fusion; inhibition of proteolytic processing of the precursor by host cell proteases.