Entry Inhibition of Influenza Viruses with High Mannose Binding Lectin ESA-2 from the Red Alga Eucheuma serra through the Recognition of Viral Hemagglutinin

Mar Drugs. 2015 May 29;13(6):3454-65. doi: 10.3390/md13063454.

Abstract

Lectin sensitivity of the recent pandemic influenza A virus (H1N1-2009) was screened for 12 lectins with various carbohydrate specificity by a neutral red dye uptake assay with MDCK cells. Among them, a high mannose (HM)-binding anti-HIV lectin, ESA-2 from the red alga Eucheuma serra, showed the highest inhibition against infection with an EC50 of 12.4 nM. Moreover, ESA-2 exhibited a wide range of antiviral spectrum against various influenza strains with EC50s of pico molar to low nanomolar levels. Besides ESA-2, HM-binding plant lectin ConA, fucose-binding lectins such as fungal AOL from Aspergillus oryzae and AAL from Aleuria aurantia were active against H1N1-2009, but the potency of inhibition was of less magnitude compared with ESA-2. Direct interaction between ESA-2 and a viral envelope glycoprotein, hemagglutinin (HA), was demonstrated by ELISA assay. This interaction was effectively suppressed by glycoproteins bearing HM-glycans, indicating that ESA-2 binds to the HA of influenza virus through HM-glycans. Upon treatment with ESA-2, no viral antigens were detected in the host cells, indicating that ESA-2 inhibited the initial steps of virus entry into the cells. ESA-2 would thus be useful as a novel microbicide to prevent penetration of viruses such as HIV and influenza viruses to the host cells.

Keywords: Eucheuma serra; anti-influenza activity; high mannose glycan; lectin; red algae.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology*
  • Dogs
  • Enzyme-Linked Immunosorbent Assay
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza, Human / prevention & control
  • Influenza, Human / virology
  • Lectins / chemistry
  • Lectins / isolation & purification
  • Lectins / pharmacology
  • Madin Darby Canine Kidney Cells
  • Mannose-Binding Lectins / chemistry
  • Mannose-Binding Lectins / isolation & purification
  • Mannose-Binding Lectins / pharmacology*
  • Rhodophyta / chemistry*
  • Virus Internalization / drug effects

Substances

  • Antiviral Agents
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Lectins
  • Mannose-Binding Lectins