The barley lectin, horcolin, binds high-mannose glycans in a multivalent fashion, enabling high-affinity, specific inhibition of cellular HIV infection
Abstract:N-linked glycans are critical to the infection cycle of HIV, and most neutralizing antibodies target the high-mannose glycans found on the surface envelope glycoprotein-120 (gp-120). Carbohydrate-binding proteins, particularly mannose-binding lectins have also been shown to bind these glycans. Despite their therapeutic potency their ability to cause lymphocyte proliferation limits their application. In this study we report one such lectin named Horcolin (Hordeum vulgare lec… Show more
“…Similarly, the chitin elicitor receptor kinase 1 (CERK1), initially reported to directly bind chitin oligosaccharides, has been suggested to function as a co-receptor for linear (1,3)- β -D-glucan, triggering fungal immune responses in A. thaliana , recently [ 58 ]. Recently, the multivalent binding of horcolin to high-mannose glycans has been demonstrated [ 59 ]. Whether a similar function may be assigned to HvHorcH remains speculation at this point.…”
Salt stress tolerance of crop plants is a trait with increasing value for future food production. In an attempt to identify proteins that participate in the salt stress response of barley, we have used a cDNA library from salt-stressed seedling roots of the relatively salt-stress-tolerant cv. Morex for the transfection of a salt-stress-sensitive yeast strain (Saccharomyces cerevisiae YSH818 Δhog1 mutant). From the retrieved cDNA sequences conferring salt tolerance to the yeast mutant, eleven contained the coding sequence of a jacalin-related lectin (JRL) that shows homology to the previously identified JRL horcolin from barley coleoptiles that we therefore named the gene HvHorcH. The detection of HvHorcH protein in root extracellular fluid suggests a secretion under stress conditions. Furthermore, HvHorcH exhibited specificity towards mannose. Protein abundance of HvHorcH in roots of salt-sensitive or salt-tolerant barley cultivars were not trait-specific to salinity treatment, but protein levels increased in response to the treatment, particularly in the root tip. Expression of HvHorcH in Arabidopsis thaliana root tips increased salt tolerance. Hence, we conclude that this protein is involved in the adaptation of plants to salinity.
“…Similarly, the chitin elicitor receptor kinase 1 (CERK1), initially reported to directly bind chitin oligosaccharides, has been suggested to function as a co-receptor for linear (1,3)- β -D-glucan, triggering fungal immune responses in A. thaliana , recently [ 58 ]. Recently, the multivalent binding of horcolin to high-mannose glycans has been demonstrated [ 59 ]. Whether a similar function may be assigned to HvHorcH remains speculation at this point.…”
Salt stress tolerance of crop plants is a trait with increasing value for future food production. In an attempt to identify proteins that participate in the salt stress response of barley, we have used a cDNA library from salt-stressed seedling roots of the relatively salt-stress-tolerant cv. Morex for the transfection of a salt-stress-sensitive yeast strain (Saccharomyces cerevisiae YSH818 Δhog1 mutant). From the retrieved cDNA sequences conferring salt tolerance to the yeast mutant, eleven contained the coding sequence of a jacalin-related lectin (JRL) that shows homology to the previously identified JRL horcolin from barley coleoptiles that we therefore named the gene HvHorcH. The detection of HvHorcH protein in root extracellular fluid suggests a secretion under stress conditions. Furthermore, HvHorcH exhibited specificity towards mannose. Protein abundance of HvHorcH in roots of salt-sensitive or salt-tolerant barley cultivars were not trait-specific to salinity treatment, but protein levels increased in response to the treatment, particularly in the root tip. Expression of HvHorcH in Arabidopsis thaliana root tips increased salt tolerance. Hence, we conclude that this protein is involved in the adaptation of plants to salinity.
“…The binding of mannose-specific banana lectin with HIV surface protein was studied in detail and found as a promising anti-HIV lectin [ 19 ]. Horcolin, a lectin from Hordeum vulgare, showed sugar-binding specificity towards high mannose sugars (Man5/7/9) and confirmed that it can bind with recombinant gp120 and gp140 with high affinity and inhibition of HIV infection at 30–35 nM concentrations without mitogenicity [ 23 ] (Table 1 ). Fig.…”
Section: Plant Lectins With Antiviral Propertiesmentioning
Background
Carbohydrate–lectin interactions are extremely specific as the lectin is capable of recognising monomeric and oligomeric sugars in a reversible manner. It has been known for a long time that lectins have antibacterial, antifungal, and insecticidal activities. Recently, it has been reported that many lectins can prevent the virus growth by interacting with the viral envelop surface glycoprotein. Spike protein, which is found on the surface of some enveloped viruses, is heavily mannosylated and will have strong affinity for mannose specific lectins. According to the findings, lectins have a high binding affinity for the glycans of the SARS-CoV-2 spike glycoprotein, which contains N-glycosylation sites. As a result, various lectins are being researched and developed as anti-viral agents.
Results
According to our in silico studies, the amino acid residues Asn487, Tyr489, Gln493, Lys417, and Tyr505 of the receptor binding domain (RBD) of SARS-CoV-2 formed an interaction with the model lectin Lablab purpureus lectin. Similar interaction for SARS-CoV-2 spike protein was observed with Griffithsin lectin (algal source) as well. These observations demonstrate that lectins could be one of the potential molecules for neutralising coronavirus infection.
Conclusion
This review focuses on anti-viral lectins isolated and characterized from plants and algae (last 5 years) and showed anti-viral properties against HIV, Influenza, and coronaviruses.
“…Although most plant lectins with antiviral activity activate different sets of T lymphocytes and, more scarcely, B lymphocytes, they also activate both the apoptotic and necrotic pathways in many other types of healthy and cancer cells [134][135][136][137][138][139][140][141][142][143]. The cellular activation mediated by plant lectins on healthy and transformed cells elicits the release of various chemokines and/or cytokines that are, in turn, susceptible to interfere with the cytokine stimulation associated with the viral infection, e.g., HIV infection [59]. However, plant lectins readily differ from each other by their capacity to elicit a cytokine production, some of them, such as PHA, Con A, and cyanovirin-N, being more active to induce the synthesis and release of activation markers [144,145], while Man-specific GNA-like lectins, such as GNA and HHA, were virtually incapable of triggering a relevant cytokine production [145,146].…”
Section: Biomedical Perspectives For Antiviral Lectinsmentioning
Pathogenic enveloped viruses are covered with a glycan shield that provides a dual function: the glycan structures contribute to virus protection as well as host cell recognition. The three classical types of N-glycans, in particular complex glycans, high-mannose glycans, and hybrid glycans, together with some O-glycans, participate in the glycan shield of the Ebola virus, influenza virus, human cytomegalovirus, herpes virus, human immunodeficiency virus, Lassa virus, and MERS-CoV, SARS-CoV, and SARS-CoV-2, which are responsible for respiratory syndromes. The glycans are linked to glycoproteins that occur as metastable prefusion glycoproteins on the surface of infectious virions such as gp120 of HIV, hemagglutinin of influenza, or spike proteins of beta-coronaviruses. Plant lectins with different carbohydrate-binding specificities and, especially, mannose-specific lectins from the Vicieae tribe, such as pea lectin and lentil lectin, can be used as glycan probes for targeting the glycan shield because of their specific interaction with the α1,6-fucosylated core Man3GlcNAc2, which predominantly occurs in complex and hybrid glycans. Other plant lectins with Neu5Ac specificity or GalNAc/T/Tn specificity can also serve as potential glycan probes for the often sialylated complex glycans and truncated O-glycans, respectively, which are abundantly distributed in the glycan shield of enveloped viruses. The biomedical and therapeutical potential of plant lectins as antiviral drugs is discussed.
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