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

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

Sato Y1, Morimoto K2, Kubo T3, Sakaguchi T4, Nishizono A5, Hirayama M6, Hori K7.

• 1Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami-Ku, Hiroshima 731-0153, Japan. sato-y@yasuda-u.ac.jp.
• 2Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami-Ku, Hiroshima 731-0153, Japan. mori-k@yasuda-u.ac.jp.
• 3Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami-Ku, Hiroshima 731-0153, Japan. kubo-t@yasuda-u.ac.jp.
• 4Department of Virology, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8551, Japan. tsaka@hiroshima-u.ac.jp.
• 5Department of Microbiology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan. a24zono@oita-u.ac.jp.
• 6Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima 739-8528, Japan. hirayama@hiroshima-u.ac.jp.
• 7Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima 739-8528, Japan. kanhori@hiroshima-u.ac.jp.

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

PMID: 26035023