Herpes simplex virus (HSV) is a double-stranded DNA virus of the herpesviridae family. HSV-1 can infect the oral mucosa, eyes, nasal mucosa, oropharynx, and nervous system and may cause severe complications including blindness, atypical pneumonia, aseptic meningitis, encephalitis, and even death [1–3]. HSV-2 is commonly transmitted through the sexual route potentially causing meningitis and encephalitis [4]. Most HSV infections are asymptomatic, but serious systemic symptoms are more often seen in neonates and immune-compromised individuals [5, 6]. The incidence and severity of HSV infections in immunocompromised patients has shown an upward trend in recent years [7–9]. HSV infections are commonly treated with nucleoside analogues such as acyclovir (ACV) and pencyclovir and certain highly bioavailable prodrugs such as valacyclovir and famciclovir [10, 11]. However, these drugs might promote viral mutations leading to drug-resistant HSVs. About 5% of clinical HSV isolates from immunocompromised patients is ACV-resistant [12]. There is an urgent need to develop new drugs against HSV infection