Glycyrrhizin inhibits human parainfluenza virus type 2 replication by the inhibition of genome RNA, mRNA and protein syntheses

Drug Discov Ther. 2017 Nov 22;11(5):246-252. doi: 10.5582/ddt.2017.01048. Epub 2017 Oct 24.

Abstract

The effect of glycyrrhizin on the replication of human parainfluenza virus type 2 (hPIV-2) was examined. Cell fusion induced by hPIV-2 was inhibited by glycyrrhizin, and glycyrrhizin reduced the number of viruses released from the cells. Glycyrrhizin did not change cell morphology at 1 day of culture, but caused some damage at 4 days, as determined by the effect on actin microfilaments. However, it affected the cell viability at 1 day: about 20% of the cells were not alive by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay at 1 day of culture. Real-time polymerase chain reaction (PCR) and PCR showed that virus genome synthesis was largely inhibited. mRNA synthesis was also inhibited by glycyrrhizin. Viral protein synthesis was largely inhibited as observed by an indirect immunofluorescence study. Multinucleated giant cell formation was studied using a recombinant green fluorescence protein (GFP)-expressing hPIV-2 without matrix protein (rhPIV-2ΔMGFP). A few single cells with fluorescence were observed, but the formation of giant cells was completely blocked. Taken together, it was shown that viral genome, mRNA and protein syntheses, including F and HN proteins, were inhibited by glycyrrhizin, and consequently multinucleated giant cell formation was not observed and the infectious virus was not detected in the culture medium.

Keywords: Virus replication; medicinal plant extract; recombinant green fluorescence protein expressing hPIV-2 without matrix protein.

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Genome, Viral / drug effects
  • Giant Cells / drug effects
  • Glycyrrhizic Acid / pharmacology*
  • HN Protein / biosynthesis
  • HN Protein / drug effects
  • Macaca mulatta
  • Parainfluenza Virus 2, Human / drug effects*
  • Parainfluenza Virus 2, Human / genetics
  • Parainfluenza Virus 2, Human / metabolism
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Messenger / drug effects*
  • RNA, Messenger / metabolism
  • RNA, Viral / drug effects*
  • RNA, Viral / metabolism
  • Real-Time Polymerase Chain Reaction
  • Viral Fusion Proteins / biosynthesis
  • Viral Fusion Proteins / drug effects
  • Viral Proteins / biosynthesis
  • Viral Proteins / drug effects
  • Virus Replication / drug effects*
  • Virus Replication / genetics

Substances

  • HN Protein
  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • RNA, Viral
  • Viral Fusion Proteins
  • Viral Proteins
  • Glycyrrhizic Acid