New strategies against drug resistance to herpes simplex virus

Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets (the DNA helicase/primase (H/P) complex), new types of molecules (nature products) and new antiviral mechanisms (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of HSV. So-called “Janus” drugs with two molecular “faces” may help address the pressing need for new treatments for herpes simplex virus (HSV). The emergence of resistance to common antiviral drugs such as acyclovir is an increasing problem, especially for patients with weakened immune systems. A team led by Yu-Chen Jiang at Sichuan University, and Hui Feng, Central South University, Changsha, review key strategies for new ways to halt the multiplication of HSV. One of the most promising involves drugs that, like acyclovir, mimic the molecular components of DNA and therefore interfere with the manufacture of viral DNA. Two key DNA components are purines and pyrimidines. The Janus drug molecules have one side that mimics purines while the other side mimics pyrimidines, allowing a double-hit against virus multiplication.