Herpes simplex virus type 1 (HSV-1) virion (HSV-1)

The Herpes simplex virus type 1 (HSV-1) virion and its attachment process represent a complex multi-step mechanism required for viral entry into host cells (Agelidis & Shukla, 2020). This process is initiated by the tethering of viral glycoproteins gC and gB to host cell surface heparan sulfate proteoglycans (UniProt, 2024). Following initial attachment, the viral glycoprotein gD binds to specific entry receptors, such as Herpesvirus Entry Mediator (HVEM), Nectin-1, or 3-O-sulfated heparan sulfate (PubMed, 2021). This binding event triggers a cascade of conformational changes in the gH/gL complex and gB, ultimately leading to the fusion of the viral envelope with the host cell membrane (StatPearls, 2023). Because this process is essential for the establishment of infection, it serves as a significant therapeutic target for antiviral agents. Drugs like docosanol act by interfering with the fusion process, preventing the viral envelope from merging with the host cell plasma membrane (PubChem, 2024). Other experimental strategies include the use of neutralizing antibodies or small molecules that competitively inhibit the binding of viral glycoproteins to their respective host receptors. Targeting the attachment and entry phase is particularly effective for preventing the spread of the virus to new cells and reducing the severity of clinical manifestations like herpes labialis or keratitis. However, once the virus has entered the host cell and established latency in the nervous system, these entry inhibitors are no longer effective against the latent reservoir. Overall, the HSV-1 attachment machinery is a critical focal point for developing next-generation antivirals aimed at blocking the earliest stages of the viral life cycle.

Other names

Human herpesvirus 1HHV-1HSV-1 attachment complexHSV-1 entry machineryHSV-1 envelope glycoproteins

Inhibition of viral envelope fusion with the host cell plasma membrane; competitive inhibition of viral glycoprotein binding to host cell surface receptors (e.g., heparan sulfate, HVEM, or Nectin-1).