Herpes simplex virus 2 fusion glycoprotein complex (HSV-2 gB/gD/gH/gL complex)

The Herpes simplex virus 2 (HSV-2) fusion glycoprotein complex is the essential molecular machinery required for the virus to enter host cells and facilitate cell-to-cell spread (PNAS, 2011; MDPI, 2021). This multi-protein assembly consists of four primary glycoproteins: glycoprotein B (gB), glycoprotein D (gD), and the heterodimer formed by glycoprotein H and glycoprotein L (gH/gL) (Nature Structural & Molecular Biology, 2010; NIH, 2012). The entry process is initiated when gD binds to specific host cell receptors, such as nectin-1 or herpesvirus entry mediator (HVEM), which induces a conformational change in gD (NIH, 2020; NIH, 2017). This change subsequently activates the gH/gL complex, which then triggers the primary fusogen, gB, to undergo a dramatic structural transition from a prefusion to a postfusion state, merging the viral envelope with the host cell membrane (NIH, 2019; NIH, 2021). As the core machinery for viral infection, this complex is a major therapeutic target for the development of vaccines and neutralizing monoclonal antibodies (NIH, 2014; MDPI, 2025). Drugs and antibodies targeting this complex, such as the monoclonal antibody UB-621 or the small molecule UCM05, aim to inhibit viral entry by blocking receptor binding sites or preventing the critical protein-protein interactions and conformational changes necessary for membrane fusion (NIH, 2025; MDPI, 2025). While current treatments like acyclovir target viral DNA replication, therapies directed at the fusion complex offer the potential to prevent the initial infection and reduce viral shedding (NIH, 2011). However, challenges remain due to the complex's structural plasticity and the virus's ability to establish lifelong latency, which entry inhibitors cannot currently eliminate (NIH, 2025).

Other names

HSV-2 entry complexHSV-2 core fusion machinerygB-gD-gH-gL complexHerpes simplex virus 2 entry complex

Inhibition of viral entry and membrane fusion by blocking receptor binding or preventing conformational changes and protein-protein interactions within the glycoprotein complex.