Virostatic potential of micro–nano filopodia-like ZnO structures against herpes simplex virus-1

• Published in: Antiviral research 2011-11, Vol.92 (2), p.305-312
• Main Authors: Mishra, Yogendra Kumar, Adelung, Rainer, Röhl, Claudia, Shukla, Deepak, Spors, Frank, Tiwari, Vaibhav
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - pharmacology; Biological and medical sciences; Cells, Cultured; Fibroblasts - virology; Herpes simplex virus 1; Herpes simplex virus type-1 (HSV-1); Herpesvirus 1, Human - drug effects; Humans; Medical sciences; Nanoparticles; Pharmacology. Drug treatments; Static Electricity; Virus Internalization - drug effects; Virus-cell interaction; Zinc Oxide - pharmacology; Zinc oxide structures
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2011.08.017

► Discovery of ZnO-based micro–nanostructures (MNSs) as an efficient anti-HSV agent. ► Easy to synthesize particles with MNSs to block HSV-1 infection. ► Filopodia-like assembly of these MNSs provides multivalent binding sites for HSV-1. ► MNSs block infection both in vitro and in vivo. ► MNSs show the promise of development as prophylactic as well as therapeutic anti-HSV-1 agents. Herpes simplex virus type-1 (HSV-1) entry into target cell is initiated by the ionic interactions between positively charged viral envelop glycoproteins and a negatively charged cell surface heparan sulfate (HS). This first step involves the induction of HS-rich filopodia-like structures on the cell surface that facilitate viral transport during cell entry. Targeting this initial first step in HSV-1 pathogenesis, we generated different zinc oxide (ZnO) micro–nano structures (MNSs) that were capped with multiple nanoscopic spikes mimicking cell induced filopodia. These MNSs were predicted to target the virus to compete for its binding to cellular HS through their partially negatively charged oxygen vacancies on their nanoscopic spikes, to affect viral entry and subsequent spread. Our results demonstrate that the partially negatively charged ZnO-MNSs efficiently trap the virions via a novel virostatic mechanism rendering them unable to enter into human corneal fibroblasts – a natural target cell for HSV-1 infection. The anti-HSV-1 activity of ZnO MNSs was drastically enhanced after creating additional oxygen vacancies under UV-light illumination. Our results provide a novel insight into the significance of ZnO MNSs as the potent HSV-1 inhibitor and rationalize their development as a novel topical agent for the prevention of HSV-1 infection.