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.

Potent antiviral activity of carbohydrate-specific algal and leguminous lectins from the Brazilian biodiversity

“…These lectins inhibited HIV infection through binding to high mannose (HM) oligosaccharides of enveloped glycoprotein gp120. 40 This supports our findings for the algal lectins AML, MEL and SfL, where EC 50 values showed minor differences that are associated with the number of sugar-binding epitope sites on the glycans that influence the anti-HIV activity. 40 OAA recognizes major high mannose sugars on HIV-1 showing similar EC 50 values supporting the similarities of the family.…”

“…39 In our study, AML, MEL and SfL belong to the OAAH lectin family that includes lectins from marine red algae Eucheuma serra (ESA) and Kappaphycus alvarezii (KAA) and cyanobacteria Oscillatoria agardhii (OAA). 40 OAA recognizes major high mannose sugars on HIV-1 showing similar EC 50 values supporting the similarities of the family. 40 These carbohydrate profiles indicate that this family has anti-HIV activity preferring to link α1-3 Man branched from the α1-6 Man of the penta-saccharide core, showing high affinity to HM N-glycans.…”

“…influenza virus type A consisting of a well-defined hemagglutinin (HA) and neuraminidase (NA), which can be subdivided into 18 (H1-H18) and 11 (N1-N11) types. 40 Our results are quite remarkable, since we identified a leguminous lectin DSclerL, with exquisitely high activity against influenza A (H3N2) infection with an EC 50 as low as 0.4-1.2 nM (Table 2). 6 According to the literature, humans and other vertebrates including wild birds, bats and pigs, can contract these type of viruses.…”

“…They are subdivided based on the type of envelope substructures, e.g. 40 ConA also binds to HM glycans and showed a somewhat weaker activity with an EC 50 of 41 nM, while lectins from Aspergillus oryzae (AOL) and Aleuria aurantia (AAL) that bind to fucose were less potent with EC 50 values of 50 to 100 nM. 55 Influenza virus binds to sialic acid structures present on the host cell surface, through the viral envelope.…”

Biological activity, cDNA cloning and primary structure of lectin KSA-2 from the cultivated red alga Kappaphycus striatum (Schmitz) Doty ex Silva

“…This lectin family includes: OAA from Oscillatoria agardhii NIES-240 Sato and Hori, 2009;Koharudin et al, 2011), PFL from Pseudomonas fluorescens Pf0-1 (Sato et al, 2012), MBHA from Myxococcus xanthus (Koharudin et al, 2012), BOA from Burkholderia oklahomensis (Whitley et al, 2013), KAA-2 from Kappaphycus alvarezii (Sato et al, 2011a), BCA from Boodlea coacta (Sato et al, 2011b) and ESA-2 from Eucheuma serra (Sato et al, 2015). All of them share binding specificity for high-mannose N-glycans and have commonly two or four tandem repeats consisting of highly conserved sequences, which may lead to subtle difference in the degree of inhibiting activities.…”