title: Design and development of antivirals and intervention strategies against human herpesviruses using high-throughput approach.
abstract: BACKGROUND
  Although a number of antiviral agents are licensed for treatment of some human herpesvirus (HHV) infections, effective antiviral therapy is not available for all HHVs. Additional complications are associated with approved drugs, such as toxicity and side effects, and rise in drug-resistant strains is a driving force for new drug development. Success in HHV vaccine development is limited with only vaccines against varicella-zoster virus currently in use in the clinic. In vitro, in vivo and in silico high-throughput (HTP) approaches and innovative microfluidic systems will provide novel technologies to efficiently identify and evaluate new targets and antiherpetic compounds. Coupled with HTP strategies for manipulation of herpesvirus viral genomes, these strategies will greatly accelerate the development of future antivirals as well as candidate vaccine intervention strategies.
  
  
  METHODS
  The authors provide a brief overview of the herpesvirus family and associated diseases. Further, the authors discuss the approved and investigational antiherpetic drugs in the context of current HTP technologies.
  
  
  CONCLUSIONS
  HTP technology such as microfluidic systems is crucial for the identification and validation of novel drug targets and next-generation antivirals. Current drug development is limited by the unavailability of HTP preclinical model systems. Specific advancement in the development of HTP animal-specific technology, applied in parallel, allows a more rapid evaluation of drugs at the preclinical stage. The advancement of HTP combinatorial drug therapy, especially 'Organ-on-a-Chip' approaches, will aid in the evaluation of future antiviral compounds and intervention strategies.
authors.affiliation: Texas A&M University, Health Science Center, Department of Microbial Pathogenesis and Immunology , 407 Reynolds Medical Bldg, College Station, TX 77843 , USA +1 979 845 6415 ; mcgregor@medicine.tamhsc.edu.
authors.forename: Julia
authors.initials: J
authors.lastname: Hornig
authors.forename: Alistair
authors.initials: A
authors.lastname: McGregor
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology*; D003198:Computer Simulation; D015195:Drug Design; D024882:Drug Resistance, Viral; D006564:Herpesviridae / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification; D006566:Herpesviridae Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D046210:Microfluidic Analytical Techniques; D014765:Viral Vaccines / Q000008:administration & dosage
chemical_list: D000998:Antiviral Agents; D014765:Viral Vaccines
keywords: Epstein–Barr virus; Organ-on-a-Chip; acyclovir; antivirals; bacterial Artificial Chromosome; cytomegalovirus; ganciclovir; herpes simplex; herpes simplex virus; herpesviruses; high throughput; human cytomegalovirus; microfluidic system; vaccine; varicella-zoster virus