GS-1 blocks entry of herpes viruses and more broadly inhibits enveloped viruses

Abstract

Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV) are significant global health concerns, infecting over 66% of the population. VZV causes varicella (chickenpox) and herpes zoster (shingles), while HSV leads to oral and genital herpes. Current antiviral treatments target viral replication but face limitations, such as the need for early intervention and the development of drug resistance, particularly in immunocompromised patients. Additionally, while shingles vaccines exist, their use is limited by availability, access, awareness, and cost. There is no vaccine for HSV. This study introduces GS-1, a novel formulation of undecylenic acid compounded with L-Arginine, as an entry inhibitor of enveloped viruses. In vitro studies demonstrate the antiviral activity of GS-1 against both VZV and HSV-1, with EC₅₀ values ranging from 26 μg/mL to 62 μg/mL. Additionally, GS-1 displayed antiviral activity against VZV in an ex vivo human skin model, indicating its potential as a topical antiviral agent. The unique mechanism of action of GS-1, which involved binding directly to viral particles and blocking viral entry, was also extended to another enveloped virus, zika virus (ZIKV), a member of the flavivirus family, but had limited ability to block the non-enveloped virus, rotavirus. GS-1 could offer an effective means of controlling viral infections, particularly when used as combination therapy with other antiviral agents. Future studies will focus on confirming these results in a clinical setting.