title: Entry Inhibition of Influenza Viruses with High Mannose Binding Lectin ESA-2 from the Red Alga Eucheuma serra through the Recognition of Viral Hemagglutinin.
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.
authors.affiliation: Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami-Ku, Hiroshima 731-0153, Japan. sato-y@yasuda-u.ac.jp.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami-Ku, Hiroshima 731-0153, Japan. mori-k@yasuda-u.ac.jp.
authors.forename: Kinjiro
authors.initials: K
authors.lastname: Morimoto
authors.affiliation: Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami-Ku, Hiroshima 731-0153, Japan. kubo-t@yasuda-u.ac.jp.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Virology, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8551, Japan. tsaka@hiroshima-u.ac.jp.
authors.forename: Takemasa
authors.initials: T
authors.lastname: Sakaguchi
authors.affiliation: Department of Microbiology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan. a24zono@oita-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishizono
authors.affiliation: Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima 739-8528, Japan. hirayama@hiroshima-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirayama
authors.affiliation: Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima 739-8528, Japan. kanhori@hiroshima-u.ac.jp.
authors.forename: Kanji
authors.initials: K
authors.lastname: Hori
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000517:prevention & control / Q000821:virology; D037102:Lectins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D061985:Madin Darby Canine Kidney Cells; D037241:Mannose-Binding Lectins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000461:Rhodophyta / Q000737:chemistry*; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D037102:Lectins; D037241:Mannose-Binding Lectins
keywords: Eucheuma serra; anti-influenza activity; high mannose glycan; lectin; red algae