Herpes simplex virus 1 glycoprotein D (HSV-1 gD)

Herpes simplex virus 1 glycoprotein D (HSV-1 gD) is a critical envelope protein required for the virus to enter host cells (UniProt P03172). It functions as the primary receptor-binding protein, interacting with host cell surface molecules such as Nectin-1, Herpesvirus entry mediator (HVEM), and 3-O-sulfated heparan sulfate (PubMed: 11836371). This binding event triggers a cascade of conformational changes in other viral glycoproteins, specifically the gH/gL complex and gB, leading to the fusion of the viral envelope with the host cell membrane (PubMed: 21680513). Because gD is essential for infectivity and is a major target for neutralizing antibodies, it has been a focal point for the development of prophylactic vaccines and therapeutic monoclonal antibodies. Therapeutic candidates like the monoclonal antibody HDIT101 work by blocking the interaction between gD and its receptors, effectively neutralizing the virus before it can enter the cell (ClinicalTrials.gov: NCT04165122). Additionally, gD has been used as a key antigen in various recombinant protein and mRNA vaccine candidates aimed at preventing primary infection and reducing viral shedding. Despite its potential, the protein's structural complexity and the virus's ability to establish lifelong latency in neurons pose significant hurdles for achieving complete sterilizing immunity. Current research continues to explore gD-targeted therapies to address conditions ranging from common cold sores to severe herpetic keratitis and encephalitis.

Other names

Envelope glycoprotein DgDUS6HHV-1 gDGlycoprotein D-1

Inhibition of viral entry by competitively binding to the gD protein, thereby preventing its interaction with host receptors such as Nectin-1 and HVEM, which is required for membrane fusion.