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Mar. Drugs 2015, 13(6), 3454-3465; 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

1
Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami-Ku, Hiroshima 731-0153, Japan
2
Department of Virology, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8551, Japan
3
Department of Microbiology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan
4
Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima 739-8528, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Peer B. Jacobson
Received: 20 January 2015 / Revised: 7 May 2015 / Accepted: 22 May 2015 / Published: 29 May 2015
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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. View Full-Text
Keywords: lectin; red algae; Eucheuma serra; high mannose glycan; anti-influenza activity lectin; red algae; Eucheuma serra; high mannose glycan; anti-influenza activity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Sato, Y.; Morimoto, K.; Kubo, T.; Sakaguchi, T.; Nishizono, A.; Hirayama, M.; Hori, K. 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, 13, 3454-3465.

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