A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein.

Abstract

The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action.

• Authors: So Young Chang, Ji Hoon Park, Young Ho Kim, Jong Seong Kang, Ji-Young Min
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 471 Issue 2 Pg. 282-9 (Mar 04 2016) ISSN: 1090-2104 [Electronic] United States
• PMID: 26850850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Antiviral Agents
• Plant Extracts
• Ribonucleoproteins

Topics

• Active Transport, Cell Nucleus (drug effects, physiology)
• Animals
• Antiviral Agents (administration & dosage)
• Cell Nucleus (drug effects, metabolism)
• Dogs
• Dose-Response Relationship, Drug
• Euphorbia (chemistry)
• Humans
• Influenza A virus (drug effects, physiology)
• Influenza B virus (drug effects, physiology)
• Influenza, Human (prevention & control, virology)
• Madin Darby Canine Kidney Cells
• Plant Extracts (administration & dosage)
• Ribonucleoproteins (metabolism)
• Virus Internalization (drug effects)