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

Herpes simplex virus 1 glycoprotein D (gD) is a critical envelope protein essential for the virus's ability to enter host cells and spread between them. It serves 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. Upon binding, gD undergoes a conformational change that triggers the viral fusion machinery, consisting of glycoproteins gB and the gH/gL complex, allowing the viral envelope to fuse with the host cell membrane. Beyond entry, gD is involved in cell-to-cell spread and the formation of syncytia, which are hallmarks of HSV-1 pathogenesis in tissues like the corneal epithelium and nervous system. As a major target for neutralizing antibodies, gD has been the focus of numerous vaccine candidates and therapeutic monoclonal antibodies, such as HDIT101, aimed at preventing infection or reducing viral shedding. However, the development of effective gD-based vaccines has faced challenges, including the virus's ability to establish lifelong latency and the complexity of the immune response required for full protection. Targeting gD remains a promising strategy for developing next-generation antivirals that can overcome resistance to traditional DNA polymerase inhibitors.

Other names

Envelope glycoprotein DUS6gD-1Herpes simplex virus type 1 glycoprotein D

Inhibition of viral entry by blocking the interaction between gD and host receptors (Nectin-1, HVEM), thereby preventing the conformational change required to trigger the viral fusion machinery and neutralizing the virus.