Herpes Simplex Virus Infectivity And The Development Of Therapeutics Against Viral Invasion

Herpes Simplex Virus is one of the most commonly transmitted viral infections worldwide. HSV Type-1 and type -2 infections are known to cause painful, ulcerative lesions and blisters in the genital and oral mucosa and in severe cases can lead to blindness, encephalitis, and death. After infection HSV permanently resides within the host in a quiescent state of latency which is established in the ganglions of nerves. Once latency is established complete clearance of the virus cannot be achieved. For the past 3 decades, physicians have utilized suppressive therapy to treat HSV positive individuals. Unfortunately, suppressive treatments such as acyclovir (ACV) and other nucleoside analogs are only effective at reducing recurrent infections as they cannot clear latent infections or prevent asymptomatic shedding. The frequent emergence of acyclovir resistant HSV strains and high toxicity associated with long term usage of ACV and other nucleoside analogs regimens highlight a major limitation of the current treatment approach. To provide an alternative to suppressive therapeutics, we investigated the stages of viral entry that could be targeted to provide protection against viral invasion. As HSV pathogenesis begins with viral entry, our goal was to target this step of the viral lifecycle. By utilizing the protein kinase inhibitors ML-7, ML-9, and Blebbistatin plus the sequence specific G2 peptide and Zinc Oxide tetrapod nanoparticles, we significantly reduced viral attachment, internalization and intracellular trafficking of virus particles. In addition, cell-to-cell transmission of virus particles, the formation of multiple nucleated cells, viral glycoprotein mediated cellular fusion, and the development of disease associated with HSV infection were diminished. This study reveals that antiviral agents specifically designed to target or disrupt interactions of the virus with its receptors during the entry phase of infection can effectively serve as a new therapeutic approach for HSV treatment.