Herpes simplex virus 2 (HSV-2)

Herpes simplex virus 2 (HSV-2) is a double-stranded DNA virus belonging to the Herpesviridae family that primarily causes genital herpes infections. The mature HSV-2 virion contains a ~152 kb linear DNA genome encoding at least 74 genes, organized within an icosapentahedral capsid composed of approximately 3,000 proteins including major capsid proteins (VP5), minor capsid proteins (VP26), and triplex proteins (VP23 and VP19C). The capsid is surrounded by tegument proteins and an outer lipid bilayer envelope containing viral glycoproteins essential for cell entry, particularly gB (glycoprotein B) and the gH/gL heterodimer. While HSV-2 itself is not a direct therapeutic target, viral proteins within the virion are actively targeted by antiviral drugs. Current treatment relies primarily on nucleoside analog DNA polymerase inhibitors such as acyclovir and valacyclovir, though emerging therapies target alternative viral proteins including helicase-primase complex, ribonucleotide reductase, and cellular factors like EZH2/1 that support viral replication. Drug resistance remains a clinical challenge with prolonged antiviral therapy, necessitating development of novel therapeutic strategies.

Other names

Human herpesvirus 2 (HHV-2)

Since HSV-2 is the virus rather than a single target protein, multiple mechanisms apply to different viral proteins: nucleoside analog DNA polymerase inhibitors (acyclovir); helicase-primase inhibitors (2-amino-thiazole, thiazolylsulfonamide); ribonucleotide reductase inhibitors; glycoprotein attachment inhibitors; and emerging EZH2/1 inhibitors that enhance cellular antiviral response.