Artificial ribonucleases inactivate a wide range of viruses using their ribonuclease, membranolytic, and chaotropic-like activities

Antiviral Res. 2016 Sep:133:73-84. doi: 10.1016/j.antiviral.2016.07.014. Epub 2016 Jul 28.

Abstract

Artificial ribonucleases (aRNases) are small compounds catalysing RNA cleavage. Recently we demonstrated that aRNases readily inactivate various viruses in vitro. Here, for three series of aRNases (1,4-diazabicyclo [2.2.2]octane-based and peptide-like compounds) we show that apart from ribonuclease activity the aRNases display chaotropic-like and membranolytic activities. The levels of membranolytic and chaotropic-like activities correlate well with the efficiency of various viruses inactivation (enveloped, non-enveloped, RNA-, DNA-containing). We evaluated the impact of these activities on the efficiency of virus inactivation and found: i) the synergism between membranolytic and chaotropic-like activities is sufficient for the inactivation of enveloped viruses (influenza A, encephalitis, vaccinia viruses) for 1,4-diazabicyclo [2.2.2]octane based aRNases, ii) the inactivation of non-enveloped viruses (encephalomyocarditis, acute bee paralysis viruses) is totally dependent on the synergism of chaotropic-like and ribonuclease activities, iii) ribonuclease activity plays a leading role in the inactivation of RNA viruses by aRNases Dp12F6, Dtr12 and K-D-1, iv) peptide-like aRNases (L2-3, K-2) being effective virus killers have a more specific mode of action. Obtained results clearly demonstrate that aRNases represent a new class of broad-spectrum virus-inactivating agents.

Keywords: ABPV; Artificial ribonucleases; Chaotropic-like activity; Encephalitis virus; Influenza virus; Membranolytic activity; Ribonuclease activity; Vaccinia virus; Virus inactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Hemolysis / drug effects
  • Humans
  • Kinetics
  • Molecular Structure
  • Ribonucleases / chemistry
  • Ribonucleases / pharmacology*
  • Vaccinia virus / drug effects
  • Virus Inactivation / drug effects*
  • Viruses / drug effects*
  • Viruses / ultrastructure

Substances

  • Antiviral Agents
  • Ribonucleases