Mannose-specific plant and microbial lectins as antiviral agents: A review.

Lectins are non-immunological carbohydrate-binding proteins classified on the basis of their structure, origin, and sugar specificity. The binding specificity of such proteins with the surface glycan moiety determines their activity and clinical applications. Thus, lectins hold great potential as diagnostic and drug discovery agents and as novel biopharmaceutical products. In recent years, significant advancements have been made in understanding plant and microbial lectins as therapeutic agents against various viral diseases. Among them, mannose-specific lectins have being proven as promising antiviral agents against a variety of viruses, such as HIV, Influenza, Herpes, Ebola, Hepatitis, Severe Acute Respiratory Syndrome Coronavirus-1 (SARS-CoV-1), Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) and most recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The binding of mannose-binding lectins (MBLs) from plants and microbes to high-mannose containing N-glycans (which may be simple or complex) of glycoproteins found on the surface of viruses has been found to be highly specific and mainly responsible for their antiviral activity. MBLs target various steps in the viral life cycle, including viral attachment, entry and replication. The present review discusses the brief classification and structure of lectins along with antiviral activity of various mannose-specific lectins from plants and microbial sources and their diagnostic and therapeutic applications against viral diseases.

Characterization of a Molecularly Engineered Banlec-Type Lectin (rBTL).

Lectins are proteins that reversibly bind to carbohydrates and are commonly found across many species. The Banana Lectin (BanLec) is a member of the Jacalin-related Lectins, heavily studied for its immunomodulatory, antiproliferative, and antiviral activity. In this study, a novel sequence was generated in silico considering the native BanLec amino acid sequence and 9 other lectins belonging to JRL. Based on multiple alignment of these proteins, 11 amino acids of the BanLec sequence were modified because of their potential for interference in active binding site properties resulting in a new lectin named recombinant BanLec-type Lectin (rBTL). rBTL was expressed in E. coli and was able to keep biological activity in hemagglutination assay (rat erythrocytes), maintaining similar structure with the native lectin. Antiproliferative activity was demonstrated on human melanoma lineage (A375), evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT). rBTL was able to inhibit cellular growth in a concentration-dependent manner, in an 8-h incubation, 12 µg/mL of rBTL led to a 28.94% of cell survival compared to cell control with 100%. Through a nonlinear fit out log-concentration versus biological response, an IC50% of 3.649 µg/mL of rBTL was determined. In conclusion, it is possible to state that the changes made to the rBTL sequence maintained the structure of the carbohydrate-binding site without changing specificity. The new lectin is biologically active, with an improved carbohydrate recognition spectrum compared to nBanLec, and can also be considered cytotoxic for A375 cells.

A Comprehensive Review on Euphorbiaceae lectins: Structural and Biological Perspectives.

Euphorbiaceae, also known as the spurge family, is a large group of flowering plants. Despite being tropical natives, they are now widespread. Due to its medicinal and commercial importance, this family of plants attracted a lot of attention in the scientific community. The distinctive characteristic of the family is production of milky latex, which is a rich source of several lectins, the proteins that bind carbohydrates. Although their function is unclear, they are believed to defend plants against damaging phytopathogenic microorganisms, insects, and predatory animals. Additionally, they serve as crucial metabolic regulators under a variety of stressors. Detection, separation, purification, and characterization of lectins from the Euphorbiaceae family - mostly from the latex of plants - began over 40 years ago. This effort produced over 35 original research papers that were published. However, no systematic review that compiles these published data has been presented yet. This review summarizes and describes several procedures and protocols employed for extraction and purification of lectins belonging to this family. Physicochemical properties and biological activities of the lectins, along with their medicinal and pharmacological properties, have also been analyzed. Additionally, using examples of ricin and ricin agglutinin, we have structurally analyzed characteristics of the lectin known as Ribosome Inactivating Protein Type II (RIP-Type II) that belongs to this family. We anticipate that this review article will offer a useful compendium of information on this important family of lectins, show the scientists involved in lectin research the gaps in our knowledge, and offer insights for future research.

Selective targeting of lectins and their macropinocytosis in urothelial tumours: translation from in vitro to ex vivo.

Urinary bladder cancer can be treated by intravesical application of therapeutic agents, but the specific targeting of cancer urothelial cells and the endocytotic pathways of the agents are not known. During carcinogenesis, the superficial urothelial cells exhibit changes in sugar residues on the apical plasma membranes. This can be exploited for selective targeting from the luminal side of the bladder. Here we show that the plant lectins Jacalin (from Artocarpus integrifolia), ACA (from Amaranthus caudatus) and DSA (from Datura stramonium) selectively bind to the apical plasma membrane of low- (RT4) and high-grade (T24) cancer urothelial cells in vitro and urothelial tumours ex vivo. The amount of lectin binding was significantly different between RT4 and T24 cells. Endocytosis of lectins was observed only in cancer urothelial cells and not in normal urothelial cells. Transmission electron microscopy analysis showed macropinosomes, endosome-like vesicles and multivesicular bodies filled with lectins in RT4 and T24 cells and also in cells of urothelial tumours ex vivo. Endocytosis of Jacalin and ACA in cancer cells was decreased in vitro after addition of inhibitor of macropinocytosis 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and increased after stimulation of macropinocytosis with epidermal growth factor (EGF). Clathrin, caveolin and flotillin did not colocalise with lectins. These results confirm that the predominant mechanism of lectin endocytosis in cancer urothelial cells is macropinocytosis. Therefore, we propose that lectins in combination with conjugated therapeutic agents are promising tools for improved intravesical therapy by targeting cancer cells.

DVL, lectin from Dioclea violacea seeds, has multiples mechanisms of action against Candida spp via carbohydrate recognition domain.

Lectins are proteins of non-immunological origin with the ability to bind to carbohydrates reversibly. They emerge as an alternative to conventional antifungals, given the ability to interact with carbohydrates in the fungal cell wall inhibiting fungal growth. The lectin from D. violacea (DVL) already has its activity described as anti-candida in some species. Here, we observed the anti-candida effect of DVL on C. albicans, C. krusei and C. parapsilosis and its multiple mechanisms of action toward the yeasts. Additionally, it was observed that DVL induces membrane and cell wall damage and ROS overproduction. DVL was also able to cause an imbalance in the redox system of the cells, interact with ergosterol, inhibit ergosterol biosynthesis, and induce cytochrome c release from the mitochondrial membrane. These results endorse the potential application of DVL in developing a new antifungal drug to fight back against fungal resistance.

Interaction of sugar stabilised silver nanoparticles with Momordica charantia seed lectin, a type II ribosome inactivating protein.

Sugar-stabilised nanomaterials have received a lot of attention in cancer therapy in recent years due to their pronounced application as specific targeting agents and maximizing their therapeutic potential while bypassing off-target effects. Lectins, the carbohydrate-binding proteins, are capable of binding to receptors present on the target cell/tissue and interact with transformed glycans better than normal cells. Besides some of the lectins exhibit anticancer activity. Conjugating sugar-stabilised NPs with lectins there for is expected to multiply the potential for the early diagnosis of cancer cells and the specific release of drugs into the tumor site. Because of the prospective applications of lectin-sugar-stabilised nanoparticle conjugates, it is important to understand their molecular interaction and physicochemical properties. Momordica charantia Seed Lectin (MCL) is a type II RIP and has been known as an anti-tumor agent. Investigation of the interaction between sugar-stabilised silver nanoparticles and MCL has been performed by fluorescence spectroscopy to explore the possibility of creating an effective biocompatible drug delivery system against cancer cells. In this regard interaction between lectin and NPs should be well-preserved, while recognizing the specific cell surface sugar. Therefore experiments were carried out in the presence and absence of specific sugar galactose. Protein intrinsic fluorescence emission is quenched at ~ 20% at saturation during the interaction without any significant shift in fluorescence emission maximum. Binding experiments reveal a good affinity. Tetrameric MCL binds to a single nanoparticle. Stern-Volmer analysis of the quenching data suggests that the interaction is via static quenching leading to complex formation. Hemagglutination experiments together with interaction studies in the presence of specific sugar show that the sugar-binding site of the lectin is distinct from the nanoparticle-binding site and cell recognition is very much intact even after binding to AgNPs. Our results propose the possibility of developing MCL-silver nanoparticle conjugate with high stability and multiple properties in the diagnosis and treatment of cancer.

Photosynthesis of hybrid silver-based nanoparticles mediated lectins and evaluation of their hemagglutinating properties.

Lectins are carbohydrate-binding proteins belonging to the Leguminosae family. In this family stand out proteins extracted from species belonging to Diocleinae subtribe, which includes, for example, the seed lectin from Dioclea violacea (DVL) and the jack bean lectin Concanavalin A (ConA). Here, we report the photosynthesis of silver/silver chloride nanoparticles (NPs) assisted by ConA and DVL. The syntheses were simple processes using a green-chemistry approach. Under electron microscopy, NPs heterogeneous in size, nearly spherical and covered by a thin lectin corona, were observed. Both NPs assisted by lectins were capable to cause strong rabbit erythrocytes agglutination with the same titers of hemagglutinating activities. These results indicate that both lectins maintained their biological activities even after association with the NPs and therefore are able to interact with biological membrane carbohydrates. However, for rabbit erythrocytes treated with proteolytic enzymes were observed different titers of hemagglutinating activities, suggesting differences in the spatial arrangement of the lectins on the surface of the NPs. This study provides evidences that these hybrid lectin-coated silver/silver chloride NPs can be used for selective recognition and interaction with membrane carbohydrates and others biotechnological applications.

Partial Characterization of Lectins Purified from the Surco and Vara (Furrow and Rod) Varieties of Black Phaseolus vulgaris.

As they manifest specifically and reversibly, lectins are proteins or glycoproteins with the characteristic of agglutinating erythrocytes. Given that grain legume lectins can represent 10% of protein content and can have various biological functions, they are extensively studied. The objective of this work was to purify and partially characterize the lectins of Phaseolus vulgaris black, var surco and vara (LBBS and LBBV). Both lectin types were purified by affinity chromatography on stroma matrix, which agglutinated human erythrocytes type A, B, and O, as well as rabbit, hamster, pig, and chicken erythrocytes. Native-PAGE was employed for molecular mass determination, yielding 109.36 and 112.68 kDa for BBS and BBV, respectively. Further analyses revealed that these lectins are tetrameric glycoproteins that require Ca+2, Mn+2 and Mg+2 ions for exhibiting their hemagglutinating function, which can be inhibited by fetuin. Moreover, optimal pH was established for both lectins (10.5 for LBBS and 7-9 for LBBV), while their activity was temperature-dependent and ceased above 70 °C. Finally, the observed differences in the biochemical characteristics and bioactive functions were ascribed to the different physiological characteristics of each seed, as well as the protein itself.

Plant Lectins: A Review on their Biotechnological Potential Toward Human Pathogens.

The indiscriminate use of antibiotics is associated with the appearance of bacterial resistance. In light of this, plant-based products treating infections are considered potential alternatives. Lectins are a group of proteins widely distributed in nature, capable of reversibly binding carbohydrates. Lectins can bind to the surface of pathogens and cause damage to their structure, thus preventing host infection. The antimicrobial activity of plant lectins results from their interaction with carbohydrates present in the bacterial cell wall and fungal membrane. The data about lectins as modulating agents of antibiotic activity, potentiates the effect of antibiotics without triggering microbial resistance. In addition, lectins play an essential role in the defense against fungi, reducing their infectivity and pathogenicity. Little is known about the antiviral activity of plant lectins. However, their effectiveness against retroviruses and parainfluenza is reported in the literature. Some authors still consider mannose/ glucose/N-Acetylglucosamine binding lectins as potent antiviral agents against coronavirus, suggesting that these lectins may have inhibitory activity against SARS-CoV-2. Thus, it was found that plant lectins are an alternative for producing new antimicrobial drugs, but further studies still need to decipher some mechanisms of action.

Structure and Biological Properties of Ribosome-Inactivating Proteins and Lectins from Elder (Sambucus nigra L.) Leaves.

Ribosome-inactivating proteins (RIPs) are a group of proteins with rRNA N-glycosylase activity that catalyze the removal of a specific adenine located in the sarcin-ricin loop of the large ribosomal RNA, which leads to the irreversible inhibition of protein synthesis and, consequently, cell death. The case of elderberry (Sambucus nigra L.) is unique, since more than 20 RIPs and related lectins have been isolated and characterized from the flowers, seeds, fruits, and bark of this plant. However, these kinds of proteins have never been isolated from elderberry leaves. In this work, we have purified RIPs and lectins from the leaves of this shrub, studying their main physicochemical characteristics, sequences, and biological properties. In elderberry leaves, we found one type 2 RIP and two related lectins that are specific for galactose, four type 2 RIPs that fail to agglutinate erythrocytes, and one type 1 RIP. Several of these proteins are homologous to others found elsewhere in the plant. The diversity of RIPs and lectins in the different elderberry tissues, and the different biological activities of these proteins, which have a high degree of homology with each other, constitute an excellent source of proteins that are of great interest in diagnostics, experimental therapy, and agriculture.

Plant lectins: A new antimicrobial frontier.

Pathogenic bacteria, viruses, fungi, parasites, and other microbes constantly change to ensure survival. Several pathogens have adopted strict and intricate strategies to fight medical treatments. Many drugs, frequently prescribed to treat these pathogens, are becoming obsolete and ineffective. Because pathogens have gained the capacity to tolerate or resist medications targeted at them, hence the term antimicrobial resistance (AMR), in that regard, many natural compounds have been routinely used as new antimicrobial agents to treat infections. Thus, plant lectins, the carbohydrate-binding proteins, have been targeted as promising drug candidates. This article reviewed more than 150 published papers on plant lectins with promising antibacterial and antifungal properties. We have also demonstrated how some plant lectins could express a synergistic action as adjuvants to boost the efficacy of obsolete or abandoned antimicrobial drugs. Emphasis has also been given to their plausible mechanism of action. The study further reports on the immunomodulatory effect of plant lectins and how they boost the immune system to curb or prevent infection.

Plant lectin: A promising future anti-tumor drug.

Since the early discovery of plant lectins at the end of the 19th century, and the finding that they could agglutinate erythrocytes and precipitate glycans from their solutions, many applications and biological roles have been described for these proteins. Later, the observed erythrocytes clumping features were attributed to the lectin-cell surface glycoconjugates recognition. Neoplastic transformation leads to various cellular alterations which impact the growth of the cell and its persistence, among which is the mutation in the outer surface glycosylation signatures. Quite a few lectins have been found to act as excellent biomarkers for cancer diagnosis while some were presented with antiproliferative activity that initiated by lectin binding to the respective glycocalyx receptors. These properties are blocked by the hapten sugar that is competing for the lectin affinity binding site. In vitro investigations of lectin-cancer cell's glycocalyx interactions lead to a series of immunological reactions that result in autophagy or apoptosis of the transformed cells. Mistletoe lectin, an agglutinin purified from the European Viscum album is the first plant lectin employed in the treatment of cancer to enter into the clinical trial phases. The entrapment of lectin in nanoparticles besides other techniques to promote bioavailability and stability have also been recently studied. This review summarizes our up-to-date understanding of the future applications of plant lectins in cancer prognosis and diagnosis. With the provision of many examples of lectins that exhibit anti-neoplastic properties.

Expression of Modified Snowdrop Lectin (Galanthus nivalis Agglutinin) Protein Confers Aphids and Plutella xylostella Resistance in Arabidopsis and Cotton.

Cotton is a major fiber crop in the world that can be severely infested by pests in agricultural fields. Identifying new insect-resistance genes and increasing the expression of known insect-resistance genes are imperative in cultivated cotton. Galanthus nivalis agglutinin (GNA), a lectin that is toxic to both chewing and sucking pests, is mainly expressed in monocotyledons. It is necessary to improve the expression of the GNA protein and to test whether the lectin confers insect resistance to dicotyledons plants. We report a modified GNA gene (ASGNA) via codon optimization, its insertion into Arabidopsis thaliana, and transient expression in cotton to test its efficacy as an insect-resistance gene against cotton aphids and Plutella xylostella. The amount of ASGNA in transgenic plants reached approximately 6.5 µg/g of fresh weight. A feeding bioassay showed that the survival rate of aphids feeding on the leaves of ASGNA transgenic plants was lower than those of aphids feeding on the leaves of non-optimized GNA (NOGNA) transgenic plants and wild-type plants. Meanwhile, the fertility rate was 36% when fed on the ASGNA transgenic plants, while the fertility was 70% and 95% in NOGNA transgenic plants and wild-type plants. Correspondingly, the highest mortality of 55% was found in ASGNA transgenic lines, while only 35% and 20% mortality was observed in NOGNA transgenic plants and wild-type plants, respectively. Similar results were recorded for aphids feeding on cotton cotyledons with transient expression of ASGNA. Taken together, the results show that ASGNA exhibited high insecticidal activity towards sap-sucking insects and thus is a promising candidate gene for improving insect resistance in cotton and other dicotyledonous plants.

Lens culinaris agglutinin inhibits human hepatoma cell migration via mannose and fucose-mediated ERK1/2 and JNK1/2/3 signalling pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is the main types of primary liver cancer, which shows some abnormal glycosylation, such as the increase of fucose. Lens culinaris agglutinin (LCA), a natural plant lectin that can bind to mannose and fucose, has been reported to be antiproliferative to may tumors. However, the effect of LCA on the vitality and migration ability of human hepatoma cells is not demonstrated. Therefore, the aim of this study is to investigate the effects of LCA on vitality and migration in human hepatoma cells and its potential mechanisms. METHODS AND RESULTS: LCA had no significant effect on viability of human hepatoma cells (HCCLM3, MHCC97L and HepG2) and hepatocytes (L02) by CCK-8 kit, but it could inhibit human hepatoma cells migration significantly without affecting hepatocytes by Transwell method. Sugar inhibition assay was used to verify the possible binding site between LCA and human hepatoma cells. The result showed that Mannose- and fucose- related sites were associated with LCA inhibiting human hepatoma cells migration. Moreover, LCA could affect HCCLM3 migration by activating ERK1/2 and JNK1/2/3 signalling pathways. LCA did not affect MMP-2 and MMP-9 of HCCLM3 through gelatinase zymography. However, the results of immunofluorescence standing showed that LCA could reduce the F-actin formation in HCCLM3 via ERK1/2 and JNK1/2/3 signalling pathways. CONCLUSIONS: LCA might inhibit human hepatoma cell migration by reducing the F-actin formation via the mannose and fucose-mediated ERK1/2 and JNK1/2/3 signalling pathway. This result will deepen people's understanding on plant lectin as a drug in tumor glycobiology.

Nostoc muscorum is a novel source of microalgal lectins with potent antiviral activity against herpes simplex type-1.

In our survey for a new antiviral agent, two types of lectin were purified from Nostoc muscorum using both ion-exchange and affinity columns chromatography. Nostoc muscorum lectins (NMLs) are categorized based on their carbohydrate preference. Nostoc muscorum lectin-1(NML-1) exhibited a strict binding specificity for complex glycoproteins without linked carbohydrates, and the other displayed specificity for α- glycosides mannose polymers (NML-2) and was classified as a glycoprotein with 16.8% linked carbohydrates. NML-1 displayed a single band of 166 kDa on native-PAGE and two bands of 81 kDa and 85 kDa on SDS-PAGE, which confirmed the heterodimeric nature of this lectin. While NML-2 is a 50 kDa glycoprotein composed of 25 kDa subunits. Physical characterization of NML-1 displayed its stability at a higher temperature of 90 °C for 5 min and over a wide pH range (4-9), while MNL-2 displayed stability up to a temperature of 80 °C for 25 min and a pH range of 5-8. NML-1 didn't require metal ions for agglutination activity, while the activity of NML-2 was doubled by manganese ions. The antiviral activity of two lectins was assessed against herpes simplex type-1 (HSV-1) using a plaque assay which revealed that NML-1 inhibited HSV-1 infection at an early stage in contrast to NML-2 which exerted its antiviral effect at the late stage of infection. These results suggest that Nostoc muscorum is a unique lead for antiviral drug discovery as it is a novel source for antiviral lectins with different modes of action.

Investigations on the Biological Activity of Allium sativum Agglutinin (ASA) Isolated from Garlic.

BACKGROUND: Garlic (Allium sativum) from the family Amaryllidaceae is widely used in culinary and is reported to have potential anticancer, anti-diabetic, antimicrobial, and cardioprotective activities. Allium sativum agglutinin (ASA) is a bulb-type lectin (BTL) domaincontaining lectin isolated from garlic and has been studied for its various biological functions. Previous studies have reported the anti-cancer effects of ASA on histiocytic lymphoma (U937), promyelocytic leukemia (HL60), and oral cancer (KB). METHODS: In this study, we have purified and characterized ASA and evaluated it for its anticancer effects on other cancer cell lines. MTT assay and FACS analysis was done to corroborate the anticancer findings against cervical (HeLa) and lung cancer (A549) cell lines. RESULTS: IC50 value of 37 µg/ml in HeLa and a weak activity (26.4 ± 1.9% cellular inhibition at 100µg/ml treatment) in A549 were found in the MTT assay. FACS analysis further corroborated these findings and showed the apoptotic effects of ASA in these cell lines. CONCLUSION: Anticancer activity for members of bulb-type lectin (BTL) domain-containing lectins has been widely reported, and we hope that our study forms a basis for the development of ASA as a therapeutic agent.

A novel plant lectin, NTL-125, interferes with SARS-CoV-2 interaction with hACE2.

COVID-19 caused by SARS-CoV-2 virus has had profound impact on the world in the past two years. Intense research is going on to find effective drugs to combat the disease. Over the past year several vaccines were approved for immunization. But SARS-CoV-2 being an RNA virus is continuously mutating to generate new variants, some of which develop features of immune escape. This raised serious doubts over the long-term efficacy of the vaccines. We have identified a unique mannose binding plant lectin from Narcissus tazetta bulb, NTL-125, which effectively inhibits SARS-CoV-2 replication in Vero-E6 cell line. In silico docking studies revealed that NTL-125 has strong affinity to viral Spike RBD protein, preventing it from attaching to hACE2 receptor, the gateway to cellular entry. Binding analyses revealed that all the mutant variants of Spike protein also have stronger affinity for NTL-125 than hACE2. The unique α-helical tail of NTL-125 plays most important role in binding to RBD of Spike. NTL-125 also interacts effectively with some glycan moieties of S-protein in addition to amino acid residues adding to the binding strength. Thus, NTL-125 is a highly potential antiviral compound of natural origin against SARS-CoV-2 and may serve as an important therapeutic for management of COVID-19.

H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice.

H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. H84T BanLec dimers bind glycoproteins containing high-mannose N-glycans on the virion envelope, blocking attachment, entry, uncoating, and spread. It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. Human skin was obtained from reduction mammoplasties and prepared for culture. Skin was infected and cultured up to 14 days. H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. Additionally, H84T BanLec arrested virus spread when treatment was delayed. Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. This is the first demonstration of H84T BanLec effectiveness against DNA viruses. H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses.

Plant lectins as prospective antiviral biomolecules in the search for COVID-19 eradication strategies.

Lectins or clusters of carbohydrate-binding proteins of non-immune origin are distributed chiefly in the Plantae. Lectins have potent anti-infectivity properties for several RNA viruses including SARS-CoV-2. The primary purpose of this review is to review the ability of lectins mediated potential biotherapeutic and bioprophylactic strategy against coronavirus causing COVID-19. Lectins have binding affinity to the glycans of SARS-COV-2 Spike glycoprotein that has N-glycosylation sites. Apart from this, the complement lectin pathway is a "first line host defense" against the viral infection that is activated by mannose-binding lectins. Mannose-binding lectins deficiency in serum influences innate immunity of the host and facilitates infectious diseases including COVID-19. Our accumulated evidence obtained from scientific databases particularly PubMed and Google Scholar databases indicate that mannose-specific/mannose-binding lectins (MBL) have potent efficacies like anti-infectivity, complement cascade induction, immunoadjuvants, DC-SIGN antagonists, or glycomimetic approach, which can prove useful in the strategy of COVID-19 combat along with the glycobiological aspects of SARS-CoV-2 infections and antiviral immunity. For example, plant-derived mannose-specific lectins BanLac, FRIL, Lentil, and GRFT from red algae can inhibit and neutralize SARS-CoV-2 infectivity, as confirmed with in-vitro, in-vivo, and in-silico assessments. Furthermore, Bangladesh has a noteworthy resource of antiviral medicinal plants as well as plant lectins. Intensifying research on the antiviral plant lectins, adopting a glyco-biotechnological approach, and with deeper insights into the "glycovirological" aspects may result in the designing of alternative and potent blueprints against the 21st century's biological pandemic of SARS-CoV-2 causing COVID-19.

Immunomodulatory Effects of Jacalin, a Dietary Plant Lectin on the Peripheral Blood Mononuclear Cells (PBMCs).

The tumor microenvironment that refers to the tumor's surroundings is a key modulator of tumor growth and invasion. The tumor-derived signals are known to downregulate the anti-tumor effects of the effector cells present in the TME. Thus, the cross-talk between the tumor cells with the surrounding immune cells helps in evading the tumor surveillance as well as aiding in tumor growth and proliferation. Hence, knowledge regarding the effects of drugs/compound on the tumor-stromal interactions is gaining importance. In the present study, the effects of jacalin, a dietary lectin on the proliferation and cytokine production of peripheral blood mononuclear cells (PBMCs), are investigated. Jacalin was shown to act as a mitogen of PBMCs, the key cytokine secreting immune cells. Also, jacalin initially induced increased mRNA expression of pro-inflammatory cytokine IFN-γ; however, prolonged stimulation of PBMCs resulted in increased expression of anti-inflammatory cytokine, mainly TGF-ß. Furthermore, 6 h jacalin prestimulated PBMCs (Jac-PBMCs) were shown to inhibit HeLa cell proliferation while 24 h Jac-PBMCs were found to favor tumor growth. Thus, it may be postulated that while jacalin initially polarizes the PBMCs to hinder the tumor growth, after a stipulated time point, interaction of jacalin with PBMCs can lead to an immunosuppressive TME that may probably assist in tumor growth and progression.