Man-Specific Lectins from Plants, Fungi, Algae and Cyanobacteria, as Potential Blockers for SARS-CoV, MERS-CoV and SARS-CoV-2 (COVID-19) Coronaviruses: Biomedical Perspectives

Betacoronaviruses, responsible for the “Severe Acute Respiratory Syndrome” (SARS) and the “Middle East Respiratory Syndrome” (MERS), use the spikes protruding from the virion envelope to attach and subsequently infect the host cells. The coronavirus spike (S) proteins contain receptor binding domains (RBD), allowing the specific recognition of either the dipeptidyl peptidase CD23 (MERS-CoV) or the angiotensin-converting enzyme ACE2 (SARS-Cov, SARS-CoV-2) host cell receptors. The heavily glycosylated S protein includes both complex and high-mannose type N-glycans that are well exposed at the surface of the spikes. A detailed analysis of the carbohydrate-binding specificity of mannose-binding lectins from plants, algae, fungi, and bacteria, revealed that, depending on their origin, they preferentially recognize either complex type N-glycans, or high-mannose type N-glycans. Since both complex and high-mannose glycans substantially decorate the S proteins, mannose-specific lectins are potentially useful glycan probes for targeting the SARS-CoV, MERS-CoV, and SARS-CoV-2 virions. Mannose-binding legume lectins, like pea lectin, and monocot mannose-binding lectins, like snowdrop lectin or the algal lectin griffithsin, which specifically recognize complex N-glycans and high-mannose glycans, respectively, are particularly adapted for targeting coronaviruses. The biomedical prospects of targeting coronaviruses with mannose-specific lectins are wide-ranging including detection, immobilization, prevention, and control of coronavirus infection.

Predictive structure and protein-ligand interface of novel lectin from rice bean (Vigna umbellata)

Lectins are an important group of multivalent glycoproteins having the property of selectively recognizing and precipitating glycoconjugates. Although lectins have been reported from diverse biological sources, legume lectins is the best-characterized family of plant lectins. We have successfully cloned and sequenced the RbL ORF of 843bp from immature rice bean seeds (Vigna umbellata). We report the results of in silico analysis of novel lectin precursor of 280 amino acids from rice bean. BlastP analysis revealed more than 90% sequence similarity of RbL protein with Vigna angularis lectin and Vigna aconitifolia lectin. ProtParam analysis revealed acidic, stable and hydrophobic nature of RbL protein. Template based 3D structure of RbL protein was modeled using I-TASSER tool and validated as good quality model. Structural analysis revealed the presence of β-sandwich (Jelly roll fold or lectin fold) in modeled RbL structure. RbL protein was functionally annotated as a plant defense protein. Molecular docking was performed to analyze interactions of RbL protein with predicted ligands (N-acetyl-D-glucosamine β-galactose, Lactose and Adenine) and two selected ligands (Glucose and Mannose). Molecular dynamics (MD) simulations of RbL-ligand complexes confirmed robust hydrogen bonding interactions between ligands and RbL protein. The novel information generated in the study would be useful in exploring RbL protein for different biomedical and biotechnological applications.

Are Dietary Lectins Relevant Allergens in Plant Food Allergy?

Lectins or carbohydrate-binding proteins are widely distributed in seeds and vegetative parts of edible plant species. A few lectins from different fruits and vegetables have been identified as potential food allergens, including wheat agglutinin, hevein (Hev b 6.02) from the rubber tree and chitinases containing a hevein domain from different fruits and vegetables. However, other well-known lectins from legumes have been demonstrated to behave as potential food allergens taking into account their ability to specifically bind IgE from allergic patients, trigger the degranulation of sensitized basophils, and to elicit interleukin secretion in sensitized people. These allergens include members from the different families of higher plant lectins, including legume lectins, type II ribosome-inactivating proteins (RIP-II), wheat germ agglutinin (WGA), jacalin-related lectins, GNA (Galanthus nivalis agglutinin)-like lectins, and Nictaba-related lectins. Most of these potentially active lectin allergens belong to the group of seed storage proteins (legume lectins), pathogenesis-related protein family PR-3 comprising hevein and class I, II, IV, V, VI, and VII chitinases containing a hevein domain, and type II ribosome-inactivating proteins containing a ricin B-chain domain (RIP-II). In the present review, we present an exhaustive survey of both the structural organization and structural features responsible for the allergenic potency of lectins, with special reference to lectins from dietary plant species/tissues consumed in Western countries.

The molecular mechanisms involved in lectin-induced human platelet aggregation

We have compared the effect of three legume lectins, wheat germ agglutinin (WGA),Phaseolus vulgarisagglutinin (PHA) andLens culinarisagglutinin (LCA), on the function of human platelets. We have found that WGA is more active than PHA in stimulating platelet activation/aggregation, while LCA has no effect. Studies on the mechanisms involved show that WGA and PHA induce phosphorylation/activation of PLCγ2 and increase [Ca2+]i. For the first time, it has been shown that Src/Syk pathway, the adapter protein SLP-76 and the exchange protein VAV, participate in the PLCγ2 activation by these lectins. Moreover WGA and PHA stimulate the PI3K/AKT pathway. PI3K, through its product phosphatidylinositol-3,4,5-trisphosphate activates Bruton’s tyrosine kinase (BTK) and contributes to PLCγ2 activation. In conclusion, our findings suggest that PLCγ2 activation induced by WGA and PHA is regulated by Src/Syk and by PI3K/BTK pathways through their concerted action.