Synergy evaluation of anti-Herpes Simplex Virus type 1 and 2 compounds acting on different steps of virus life cycle

Antiviral Res. 2018 Mar;151:71-77. doi: 10.1016/j.antiviral.2018.01.009. Epub 2018 Jan 31.

Abstract

Despite the clinical need of novel and safe anti-herpetic compounds effective for treating both primary infections and reactivations of Herpes Simplex Virus type 1 (HSV-1) and type 2 (HSV-2), the development of novel antivirals approved for clinical administration has been limited in the last decades to improvements of nucleoside analogues compounds. In this context, targeting different steps of the herpesvirus life cycle, including entry and cell-to-cell infection, can represent an important starting point for obtaining more efficient infection inhibition, and for overcoming both drug resistance and toxicity. Under these perspectives, testing possible synergy between drugs currently in clinical use and novel immunotherapeutics, such as neutralizing human monoclonal antibodies, represents a fascinating option. In the study here described we tested for the first-time possible combinations of inhibitors of Herpesvirus DNA synthesis and a human neutralizing IgG able to block also cell-to-cell infection, by analysing experimental results with different mathematical models. The present study clearly highlights the synergism between all anti-herpetic drugs tested in combination with the mAb; this strongly suggests possible reduction of anti-herpetic drugs combined with the IgG for overcoming drug-related side effects, as indicated by Drug Reduction Index.

Keywords: Antiherpetic drug; Cell-to-cell transmission; Drug reduction index; HSV; Human monoclonal antibody; Synergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Neutralizing / pharmacology*
  • Antibodies, Viral / pharmacology
  • Antiviral Agents / pharmacology*
  • Chlorocebus aethiops
  • Drug Synergism
  • Herpes Simplex / virology*
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / immunology
  • Herpesvirus 1, Human / physiology
  • Herpesvirus 2, Human
  • Inhibitory Concentration 50
  • Vero Cells
  • Virus Internalization / drug effects
  • Virus Replication / drug effects

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antiviral Agents