Puumala virus Gc glycoprotein (Gc)

The Puumala virus Gc glycoprotein is a class II membrane fusion protein located on the viral envelope of the Puumala virus (PUUV), a member of the Hantaviridae family [6, 10]. It is generated from the proteolytic cleavage of a glycoprotein precursor (GPC) into two subunits, Gn and Gc, which subsequently form heterotetrameric spikes on the virion surface [5, 7]. The Gc subunit is primarily responsible for the pH-dependent fusion between the viral envelope and the host endosomal membrane, a process essential for releasing the viral genome into the host cell cytoplasm [6, 12]. PUUV is the leading cause of nephropathia epidemica, a form of hemorrhagic fever with renal syndrome (HFRS) characterized by acute kidney injury and increased vascular permeability [12, 16]. As the principal target for the host's neutralizing antibody response, the Gc glycoprotein is a major focus for therapeutic and prophylactic development [3, 8]. Experimental monoclonal antibodies, such as ADI-42898 and P-4G2, have been shown to neutralize PUUV by binding to the Gc subunit and preventing the conformational rearrangements necessary for membrane fusion [4, 15]. While several vaccine candidates, including those based on virus-like particles (VLPs) and mRNA technology, are currently under investigation, there are no FDA-approved vaccines or specific antiviral drugs targeting the Gc glycoprotein to date [8, 12].

Other names

Glycoprotein G2Envelope glycoprotein GcPuumala orthohantavirus GcM polyprotein Gc subunit

Neutralization of viral entry by binding to the pre-fusion conformation of Gc, preventing fusogenic rearrangements and perturbing the Gn-Gc lattice [3, 4, 8].