Glycan-directed SARS-CoV-2 inhibition by leek extract and lectins with insights into the mode-of-action of Concanavalin A.

Four years after its outbreak, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global challenge for human health. At its surface, SARS-CoV-2 features numerous extensively glycosylated spike proteins. This glycan coat supports virion docking and entry into host cells and at the same time renders the virus less susceptible to neutralizing antibodies. Given the high genetic plasticity of SARS-CoV-2 and the rapid emergence of immune escape variants, targeting the glycan shield by carbohydrate-binding agents emerges as a promising strategy. However, the potential of carbohydrate-targeting reagents as viral inhibitors remains underexplored. Here, we tested seven plant-derived carbohydrate-binding proteins, called lectins, and one crude plant extract for their antiviral activity against SARS-CoV-2 in two types of human lung cells: A549 cells ectopically expressing the ACE2 receptor and Calu-3 cells. We identified three lectins and an Allium porrum (leek) extract inhibiting SARS-CoV-2 infection in both cell systems with selectivity indices (SI) ranging between >2 and >299. Amongst these, the lectin Concanavalin A (Con A) exerted the most potent and broad activity against a panel of SARS-CoV-2 variants. We used multiplex super-resolution microscopy to address lectin interactions with SARS-CoV-2 and its host cells. Notably, we discovered that Con A not only binds to SARS-CoV-2 virions and their host cells, but also causes SARS-CoV-2 aggregation. Thus, Con A exerts a dual mode-of-action comprising both, antiviral and virucidal, mechanisms. These results establish Con A and other plant lectins as candidates for COVID-19 prevention and basis for further drug development.

Omentin-1 inhibits the development of benign prostatic hyperplasia by attenuating local inflammation.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland. METHODS: Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1-/-) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay. RESULTS: In vivo, Itln-1-/- mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation. CONCLUSION: The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.

Proteome Analysis of Serum Purified Using Solanum tuberosum and Lycopersicon esculentum Lectins.

Serum and plasma exhibit a broad dynamic range of protein concentrations, posing challenges for proteome analysis. Various technologies have been developed to reduce this complexity, including high-abundance depletion methods utilizing antibody columns, extracellular vesicle enrichment techniques, and trace protein enrichment using nanobead cocktails. Here, we employed lectins to address this, thereby extending the scope of biomarker discovery in serum or plasma using a novel approach. We enriched serum proteins using 37 different lectins and subjected them to LC-MS/MS analysis with data-independent acquisition. Solanum tuberosum lectin (STL) and Lycopersicon esculentum lectin (LEL) enabled the detection of more serum proteins than the other lectins. STL and LEL bind to N-acetylglucosamine oligomers, emphasizing the significance of capturing these oligomer-binding proteins when analyzing serum trace proteins. Combining STL and LEL proved more effective than using them separately, allowing us to identify over 3000 proteins from serum through single-shot proteome analysis. We applied the STL/LEL trace-protein enrichment method to the sera of systemic lupus erythematosus model mice. This revealed differences in >1300 proteins between the systemic lupus erythematosus model and control mouse sera, underscoring the utility of this method for biomarker discovery.

Reversal mechanism of multidrug-resistant cancer cells by lectin as chemo-adjuvant and targeted therapy- a systematic review.

BACKGROUND: Cancer is characterized as the leading cause of death, and the susceptibility of cancer cells to develop resistance due to long-term exposure to complementary chemotherapeutic treatment is referred to as multidrug resistance cancer cells (MDRC), which is a significant obstacle in the treatment of malignancies. Since complementary medicine lost its effectiveness, the development of potential alternative and novel therapeutic approaches has been elevated to a top priority in recent years. In this context, a bioactive protein lectin from plant and animal sources exhibits an invaluable source of anticancer agents with vast therapeutic potential. PURPOSE: This manuscript's primary purpose is to enlighten the evidence-based (from 1986 to 2022) possible molecular mechanism of alternative treatment approaches using lectins over the complementary medicines used for cancer treatment. METHODS: The PRISMA rules have been followed properly and qualitative and quantitative data are synthesized systematically. Articles were identified based on Clinical and preclinical reports published on lectin that investigated the in-depth cellular mechanisms, of reverse drug integrative oncology, as a nano-carried targeted delivery. Articles were systematically screened from 1986 to 2022 and selected based on electronic database searches, Medline (PubMed), Google Scholar, Web of Science, Encyclopaedias, Scopus, and ClinicalTrials.gov database. RESULTS: The search turned up 4,212 publications from 38 different nations, of which 170 reference articles were used in our analysis, in 16 combination therapy and their mode of action, and 27 clinical trial studies including dosage and mechanism of action were included. Reports from the 30 lectins belonging to 28 different families have been included. The reversal mechanism of lectin and alternative therapy against MDRC is critically screened and according to a few clinical and preclinical reports, lectin can suppress the overexpressing genes like P-53, EGFR, and P-gp, MRP, and ABC transporter proteins associated with intracellular transportation of drugs. Since, the drug efflux mechanism leads to MDRC, in this phenomenon, lectin plays a key role in reversing the efflux mechanism. Few preclinical reports have mentioned that lectin shows synergism in combination with complementary medicine and as a nano drug carrier helps to deliver to the targeted site. CONCLUSION: We have discussed the alternative therapy using lectin and an in-depth insight into the reversal drug resistance mechanisms to combat MDRC cancer, enhance the efficacy, reduce toxicity and adverse events, and ensure targeted delivery, and their application in the field of cancer diagnosis and prognosis has been discussed. However, further investigation is necessary in drug development and clinical trials which could be helpful to elaborate the reversal mechanism and unlock newer treatment modalities in MDRC cancer.

The Importance of Traditional Chinese Medicine in the Intervention and Treatment of HIV while Considering its Safety and Efficacy.

Natural products have been considered a potential resource for the development of novel therapeutic agents, since time immemorial. It is an opportunity to discover cost-effective and safe drugs at the earliest, with the goal to hit specific targets in the HIV life cycle. Natural products with inhibitory activity against human immunodeficiency virus are terpenes, coumarins, flavonoids, curcumin, proteins, such as lectins, laccases, bromotyrosines, and ribosome-inactivating proteins. Terpenes inhibit virus fusion, lectins and flavonoids have an inhibitory impact on viral binding, curcumin and flavonoids inhibit viral DNA integration. The most important medicinal plants which have been used in traditional Chinese medicinal sciences with anti-HIV properties are Convallaria majalis, Digitalis lanata, Cassia fistula, Croton macrostachyus, Dodonaea angustifolia, Ganoderma lucidum, Trametes versicolor, Coriolus versicolor, Cordyceps sinensis, Gardenia jasminoides, Morus alba, Scutellaria baicalensis, Ophiopogon japonicus, Platycodon grandiflorus, Fritillaria thunbergii, Anemarrhena asphodeloides, Trichosanthes kirilowii, Citrus reticulata, Glycyrrhiza uralensis, Rheum officinale, Poria cocos, Rheum palmatum, Astragalus membranaceus, Morinda citrifolia, Potentilla kleiniana, Artemisia capillaris, Sargassum fusiforme, Piperis longi fructus, Stellera chamaejasme, Curcumae rhizoma, Dalbergia odorifera lignum, Arisaematis Rhizoma preparatum, and Phellodendron amurense. The information provided is gathered from randomized control experiments, review articles, and analytical studies and observations, which are obtained from different literature sources, such as Scopus, Google Scholar, PubMed, and Science Direct from July 2000 to August 2023. The aim of this review article is to survey and introduce important medicinal plants and herbs that have been used for the treatment of HIV, especially the medicinal plants that are common in traditional Chinese medicine, as research to date is limited, and more evidence is required to confirm TCM,s efficacy.

Toxicity and antitumor activity of the water-soluble lectin from Moringa oleifera Lam. Seeds (WSMoL) in sarcoma 180-bearing mice.

WSMoL, a water-soluble lectin from the seeds of Moringa oleifera, present several biological activities. This work aimed to evaluated the toxicity and antitumor activity of WSMoL. To analyze toxicity, it was determined hematological, biochemical and histological parameters; consumption of water and feed as well as the weight of the animals. Antitumor analysis included evaluation of tumor weight, histology and cytokine levels. Acute toxicity assay revealed 60% mortality of animals treated with lectin at 200 mg/kg i. p. At 100 mg/kg i. p., the animals showed a decreased food and water consumption as well weight gain in comparison with control. However, no animal died and there were no alterations in blood parameters or histological analysis. Antitumor activity evaluated at safe doses (2.5, 5 and 10 mg/kg) showed a significant reduction in tumor weight. Tumor photomicrographs evidenced that WSMoL treatment reduced dissemination of tumor cells. WSMoL (5 and 10 mg/kg) significantly enhance the immune function in the tumor environment as showed by increased the levels of pro-inflammatory (TNF-α, IFN-γ, IL-2, IL-6, and IL-17) and anti-inflammatory (IL-4 and IL-10) cytokines. In conclusion, WSMoL showed in vivo antitumor activity in mice bearing sarcoma 180 tumor, probably by increase the immune response against the tumor.

Jackfruit waste: an invented anticancer therapy using Jacalin lectin from jackfruit seed.

Every food source contains both edible and inedible waste components. Millions of tonnes of trash from the food business are made from fruits, and these wastes are containing higher-value medicinal components, such as alkaloids, flavonoids, phenolic contents, a huge amount of proteins and secondary metabolites. These bioactive phytoconstituents are being used for the treatment of many serious fatal diseases. So, utilizing the recovered bioactive molecules from food wastes as functional ingredients offers a long-term alternative source of therapeutically active components that will lead to the discovery of novel phytoconstituents or novel treatment approaches. The goal of this systematic study is to provide an overview of the jackfruit (Artocarpus heterophyllus Lam, Moraceae) edible byproducts, such as jackfruit seeds that are largely neglected. This seed contains numerous bioactive lead molecules, such as carbohydrate-binding protein jacalin, which exhibits potent anticancer activity against colon cancer, blood cancer and breast cancer as well as can enlighten the new possible treatment approaches in targeted therapy and photodynamic chemotherapy. Moreover, jackfruit waste seed can be taken as a dietary food, which is having property to prevent and treat cancer and other lifestyle diseases. The works that have been carried out to utilize jackfruit waste other than the juicy edible bulbs have been reviewed in this article.

Phytochemical prospection, hemagglutinating and insecticidal activity of saline extracts from the seeds of Tamboril (Enterolobium contortisiliquum) Vell. Morong (Fabaceae) on Aedes aegypti (Diptera: Culicidae).

This study evaluated the insecticidal activity of crude extracts from Enterolobium contortisiliquum (Vell.) seeds on eggs and larvae of A. aegypti, and also verified the phytochemical profile and the presence of lectins in the extract. The 0.15 M NaCl saline solution was used as the extracting substance. For tests with eggs and larvae, the crude extract was used in its raw form (RCE) and boiled at 100º C for 5 min (BCE). Concentrations of 4.68; 9.37; 18.75; 28.13; 37.13 and 46.89 mg/mL, with distilled water as a negative control. Assays were performed in triplicate. The results were subjected to analysis of variance, Tukey's test and Log-Probit analysis to determine LC50 and LC90. BCE showed better results on eggs than RCE, managing to prevent the hatching of larvae in 81.66% ± 10.40 of treated eggs, at a concentration of 46.89 mg/mL. The LC50 and LC90 were set at 35.95 and 52.67 mg/mL, respectively. In tests with larvae, concentrations of 46.89 and 37.13 mg/mL, for RCE and BCE, caused 100% mortality in 24 hours of exposure. Larval mortality at the other concentrations increased with exposure time extending to 48 h. RCE, at 48 h exposure is the most promising extract on larvae (E = 72.77%, LC90 = 10.86 mg/mL). In RCE, the presence of lectins and secondary metabolites: flavonoids, xanthones and phenols, were detected. The results demonstrate the potential of E. contortisiliquum seed extracts with ovicidal and larvicidal action on A. aegypti.

Cath-DM-NT, a peptide derived from the skin of Duttaphrynus melanostictus, shows dual lectin-like and antioxidant activity.

Chansu, a mixture extracted from Duttaphrynus melanostictus or Bufo gargarizans Cantor, is a traditional Chinese medicine with a broad range of medical applications. However, the peptides/proteins in it have not received adequate attention. Herein, a Cathelicidin-DM-derived peptide named Cath-DM-NT was identified from the skin of D. melanostictus. Previous studies have shown that Cathelicidin-DM has significant antibacterial activity, while Cath-DM-NT has no antibacterial activity. In this study, Cath-DM-NT is found to have lectin-like activity which can agglutinate erythrocytes and bacteria, and bind to lipopolysaccharide (LPS). In addition, Cath-DM-NT has antioxidant activity, which can scavenge 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and nitric oxide (NO) radicals and reduce Fe3+. Consistently, Cath-DM-NT can protect PC12 cells from H2O2-induced oxidative damage and carrageenan-induced paw edema, reduce malondialdehyde (MDA) and reactive oxygen species (ROS) accumulation, and restore superoxide dismutase (SOD) and glutathione (GSH) levels. Our study suggests that Cath-DM-NT can serve as a lead compound for the development of drugs with dual lectin and antioxidant effects.

Heating or ginger extract reduces the content of Pinellia ternata lectin in the raphides of Pinellia tuber.

Pinellia tuber, the dried tuber of Pinellia ternata, causes a very strong acridity sensation in the oral and laryngopharynx mucosa when taken orally in its unprocessed form. In traditional Chinese medicine (TCM), this sensation has been called "toxicity", and Pinellia tuber must be processed using ginger extract, licorice, or alum. In Japanese traditional Kampo medicine, since "toxicity" can be eliminated by decocting, it should not be processed. However, little is known about the mechanism underlying the "detoxification" of Pinellia tubers. In this study, we produced murine antiserum using recombinant P. ternata lectin (PTL), developed an immuno-fluorescence staining method for PTL in the needle-shaped crystals (raphides) that were prepared by petroleum ether extraction (PEX) from Pinellia tuber, and elucidated the mechanism of the processing of Pinellia tuber using heat or ginger extract. After heating the raphides in water, the amount of PTL contained in the raphides was significantly reduced by the immunostaining, although the shape of the raphides was not changed. Incubating raphides with dried ginger extract also significantly reduced the amount of PTL in the raphides in a concentration-dependent manner. By the activity-guided fractionation of ginger extract, the active ingredients in the ginger extract were oxalic acid, tartaric acid, malic acid, and citric acid. Among these four organic acids, oxalic acid mainly contributed to the effect of dried ginger extract by its content in ginger extract and its activity. These results exhibit scientific evidences for the traditional theories of processing to "detoxify" Pinellia tuber in TCM and Kampo medicine.

Pinellia genus: A systematic review of active ingredients, pharmacological effects and action mechanism, toxicological evaluation, and multi-omics application.

The dried tuber of Pinellia ternata (Thunb.) Breit, Pinelliae Rhizoma (PR, also named 'Banxia' in Chinese), is widely used in traditional medicine. This review aims to provide detail summary of active ingredients, pharmacological effects, toxic ingredients, detoxification strategies, and omic researches, etc. Pharmacological ingredients from PR are mainly classified into six categories: alkaloids, amino acids, polysaccharides, phenylpropanoids, essential oils, and glucocerebrosides. Diversity of chemical composition determines the broad-spectrum efficacy and gives a foundation for the comprehensive utilization of P. ternata germplasm resources. The pharmacological compounds are involved in inhibition of cancer cells by targeting various pathways, including activation of immune system, inhibition of proliferation and cycle, induction of apoptosis, and inhibition of angiogenesis. The pharmacological components of PR act on nervous system by targeting neurotransmitters, activating immune system, decreasing apoptosis, and increasing redox system. Lectins, one major class of the toxic ingredients extracted from raw PR, possess significant toxic effects on human cells. Inflammatory factors, cytochrome P450 proteins (CYP) family enzymes, mammalian target of rapamycin (mTOR) signaling factors, transforming growth factor-ß (TGF-ß) signaling factors, and nervous system, are considered to be the target sites of lectins. Recently, omic analysis is widely applied in Pinellia genus studies. Plastome genome-based molecular markers are deeply used for identifying and resolving phylogeny of Pinellia genus plants. Various omic works revealed and functional identified a series of environmental stress responsive factors and active component biosynthesis-related genes. Our review summarizes the recent progress in active and toxic ingredient evaluation, pharmacological effects, detoxification strategies, and functional gene identification and accelerates efficient utilization of this traditional herb.

[Effect of lime water processing of Pinelliae Rhizoma Praeparatum on toxic component lectin protein].

The present study investigated the effect of immersion in the excipient lime water on the toxic component lectin protein and explained the scientific connotation of lime water detoxication during the processing of Pinelliae Rhizoma Praeparatum. Western blot was used to investigate the effects of immersion in lime water with different pH(pH 10, 11, and 12.4), saturated sodium hydroxide, and sodium bicarbonate solution on the content of lectin protein. The protein compositions of the supernatant and the precipitate after immersing lectin protein in lime water of different pH were determined by the SDS-PAGE method combined with the silver staining technique. The MALDI-TOF-MS/MS technique was used to detect the molecular weight distribution of peptide fragments in the supernatant and precipitate after immersing lectin protein in lime water of different pH, and circular dichroism spectroscopy was used to detect the ratio changes in the secondary structure of lectin protein during the immersion. The results showed that immersion in lime water at pH>12 and saturated sodium hydroxide solution could significantly reduce the content of lectin protein, while immersion in lime water at pH<12 and sodium bicarbonate solution had no significant effect on lectin protein content. The corresponding lectin protein bands and molecular ion peaks were not detected at the 12 kDa position in the supernatant and precipitate after immersing the lectin protein in lime water at pH>12, which was attributed to the fact that lime water immersion at pH>12 could significantly change the ratio of the secondary structure of lectin protein, resulting in irreversible denaturation, while lime water immersion at pH<12 did not change the ratio of the secondary structure of lectin protein. Therefore, pH>12 was the key condition for the detoxication of lime water during the processing of Pinelliae Rhizoma Praeparatum. Lime water immersion at pH>12 could cause irreversible denaturation of lectin protein, resulting in a significant decrease in the inflammatory toxicity of Pinelliae Rhizoma Praeparatum, which played a key role in detoxification.

Isolation of Momordica charantia seed lectin and glycosidases from the protein bodies: Lectin-glycosidase (ß-hexosaminidase) protein body membrane interaction reveals possible physiological function of the lectin.

Momordica charantia seeds are known to contain a galactose specific lectin that has been well characterized. Seed extracts also contain glycosidases such as the ß-hexosaminidase, α-mannosidase and α-galactosidase. In the present study, lectin was affinity purified from the seed extracts and protein bodies isolated by sucrose density gradient centrifugation. From the protein bodies, lectin was identified and ß-hexosaminidase was isolated by lectin affinity chromatography and subsequently separated from other glycosidases by gel filtration. In the native PAGE, the purified ß-hexosaminidase migrated as a single band with a molecular weight of ∼235 kDa and by zymogram analysis using 4-methylumbelliferyl N-acetyl-ß-D-glucosaminide substrate it was confirmed as ß-hexosaminidase. Under reducing conditions in SDS-PAGE, the purified enzyme dissociated into three bands (Mr 33, 20 and 15 kDa). The prominent bands (20 and 15 kDa) showed immunological cross-reactivity with the human Hexosaminidase B antibody in a western blot experiment. In gel digestion of the purified enzyme, followed by proteomic analysis using tandom MS/MS revealed sequence identity as compared to the genomic sequence of the Momordica charantia with a score of 57 (24% sequence coverage). Additionally, by CD analysis the purified ß-hexosaminidase showed 39.1% of α-helix. Furthermore, secondary structure variations were observed in presence of substrate, lectin and at different pH values. Protein body membrane prepared from the isolated protein bodies showed a pH dependent interaction with the purified lectin and mixture of glycosidases.

The Health-promoting Potential of Edible Mushroom Proteins.

Edible mushrooms have been classified as "next-generation food" due to their high nutritional value coupled with their biological and functional potential. The most extensively studied and reported mushroom macromolecules are polysaccharides. However, macrofungi proteins and peptides are also a representative and significant bioactive group. Several factors such as species, substrate composition and harvest time significantly impact the mushroom protein content, typically ranging between 19 and 35% on a dry weight basis. Proteins work based on their shape and structure. Numerous extraction methods, including chemical and non-conventional, and their implications on protein yield and stability will be discussed. Beyond their biological potential, a great advantage of mushroom proteins is their uniqueness, as they often differ from animal, vegetable, and microbial proteins. According to recently published reports, the most relevant mushroom bioactive proteins and peptides include lectins, fungal immunomodulatory proteins, ubiquitin-like proteins, and proteins possessing enzymatic activity such as ribonucleases laccases, and other enzymes and ergothioneine. These are reported as antioxidant, antiviral, antifungal, antibacterial, antihypertensive, immunomodulatory, antitumour, antihypercholesterolemic or antihyperlipidemic, antidiabetic and anti-inflammatory properties, which improved proteins and peptides research interest and contributed to the increase of mushroom market value. This review provides an overview of the most relevant biochemical and biological properties of the main protein groups in edible mushrooms, explicitly focusing on their biomedical potential. Although mushrooms are a rich source of various proteins, many of these molecules have yet to be identified and characterised. Accordingly, it is crucial to identify and characterise new macromolecules of macrofungi origin, which opens an opportunity for further investigation to identify new bioactives for food, nutraceutical, or medicinal applications.

Lectin-based phototherapy targeting cell surface glycans for pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is resistant to current treatments but lectin-based therapy targeting cell surface glycans could be a promising new horizon. Here, we report a novel lectin-based phototherapy (Lec-PT) that combines the PDAC targeting ability of rBC2LCN lectin to a photoabsorber, IRDye700DX (rBC2-IR700), resulting in a novel and highly specific near-infrared, light-activated, anti-PDAC therapy. Lec-PT cytotoxicity was first verified in vitro with a human PDAC cell line, Capan-1, indicating that rBC2-IR700 is only cytotoxic upon cellular binding and exposure to near-infrared light. The therapeutic efficacy of Lec-PT was subsequently verified in vivo using cell lines and patient-derived, subcutaneous xenografting into nude mice. Significant accumulation of rBC2-IR700 occurs as early as 2 hours postintravenous administration while cytotoxicity is only achieved upon exposure to near-infrared light. Repeated treatments further slowed tumor growth. Lec-PT was also assessed for off-target toxicity in the orthotopic xenograft model. Shielding of intraperitoneal organs from near-infrared light minimized off-target toxicity. Using readily available components, Lec-PT specifically targeted pancreatic cancer with high reproducibility and on-target, inducible toxicity. Rapid clinical development of this method is promising as a new modality for treatment of pancreatic cancer.

Schinus terebinthifolia leaf lectin has central and peripheral antinociceptive action mediated by its carbohydrate-recognition domain and delta-opioid receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Preparations from the bark and leaves of Schinus terebinthifolia Raddi are commonly used to treat toothaches and sore throats. The use of medications based on leaves of this plant has also been reported for pain of arthritis, toothache, and sore throat. Some evidence indicated that the lectin SteLL is an antinociceptive agent from leaves. AIM OF THE STUDY: This study evaluated the antinociceptive activity of S. terebinthifolia leaf lectin (SteLL) using mouse models of peripheral and central nociception. MATERIALS AND METHODS: Animals were treated intraperitoneally with SteLL at 1, 5, and 10 mg/kg. An acetic acid-induced abdominal writhing test was performed to screen for the antinociceptive effect of the lectin. Next, the formalin test was used to assess the effects of SteLL on neurogenic (first phase) and inflammatory (second phase) pain, as well as to investigate the involvement of the carbohydrate-recognition domain (CRD) of SteLL and opioid receptors in the antinociceptive effect. The tail immersion test was performed to assess the central antinociception. Additionally, a rotarod test was performed to evaluate the effects of lectin on motor coordination in mice. RESULTS: SteLL reduced the number of acetic acid-induced writhes by 83.5-100.0%. In the first phase of the formalin test, SteLL reduced paw licking time by 49.4-50.5%, while in the second phase, SteLL reduced paw licking time by 80.5-82.6%. This antinociceptive effect was reversed by the previous incubation of the lectin with ovalbumin (indicating the possible involvement of the CRD) and by the administration of naloxone, a nonselective opioid receptor antagonist. When testing selective antagonists of opioid receptors (µ, δ, and κ), only naltrindole, a selective δ receptor antagonist, blocked the antinociceptive action of SteLL during the second phase of the formalin test. In the tail immersion test, SteLL (1, 5, and 10 mg/kg) administration reduced sensitivity to thermal stimulus, which was observed even after 2 h. SteLL (10 mg/kg) did not affect animal motor coordination in rotarod test when compared to the control group. CONCLUSION: SteLL has peripheral and central analgesic action involving opioid receptor modulation without affecting the motor coordination of animals. These results provide new perspectives for developing analgesic agents using lectins.

Tomato POLLEN DEFICIENT 2 encodes a G-type lectin receptor kinase required for viable pollen grain formation.

Pollen development is a crucial biological process indispensable for seed set in flowering plants and for successful crop breeding. However, little is known about the molecular mechanisms regulating pollen development in crop species. This study reports a novel male-sterile tomato mutant, pollen deficient 2 (pod2), characterized by the production of non-viable pollen grains and resulting in the development of small parthenocarpic fruits. A combined strategy of mapping-by-sequencing and RNA interference-mediated gene silencing was used to prove that the pod2 phenotype is caused by the loss of Solanum lycopersicum G-type lectin receptor kinase II.9 (SlG-LecRK-II.9) activity. In situ hybridization of floral buds showed that POD2/SlG-LecRK-II.9 is specifically expressed in tapetal cells and microspores at the late tetrad stage. Accordingly, abnormalities in meiosis and tapetum programmed cell death in pod2 occurred during microsporogenesis, resulting in the formation of four dysfunctional microspores leading to an aberrant microgametogenesis process. RNA-seq analyses supported the existence of alterations at the final stage of microsporogenesis, since we found tomato deregulated genes whose counterparts in Arabidopsis are essential for the normal progression of male meiosis and cytokinesis. Collectively, our results revealed the essential role of POD2/SlG-LecRK-II.9 in regulating tomato pollen development.

Antimicrobial Studies on Garlic Lectin.

Allium sativum agglutinin (ASA) is an important lectin isolated from garlic bulbs and has shown promising therapeutic potential in earlier reports. It has a bulb-type lectin domain, and members of this protein family have been investigated for anti-cancer, antimicrobial and other effects. In our earlier study, we have reported ASA as an anti-cancer agent, and in the present study, we have evaluated it for its antifungal and antimicrobial effects. The effects of ASA on the opportunistic pathogens in humans Candida auris and Candida glabrata fungal strains have been evaluated, and efforts are made to evaluate the mechanistic basis of these antifungal effects. The antifungal activity of ASA on different strains of C. glabrata and C. auris was found with MIC50 concentration range of 30-70 µg/ml. Fungal growth was significantly suppressed upon treatment with ASA at MIC50 and 2MIC50. Hydrogen peroxide production was detected after ASA treatment in fungal cells and cell morphology, and integrity was affected when analysed through FE-SEM. Further, the anti-biofilm effect of ASA was investigated against Candida and three bacterial strains (Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae), and promising results were obtained with maximal effect in case of K. pneumoniae among the bacterial strains. These results can form the basis for the development of ASA as antimicrobial agent.

Pineapple Lectin AcmJRL Binds SARS-CoV-2 Spike Protein in a Carbohydrate-Dependent Fashion.

The highly glycosylated spike protein of SARS-CoV-2 is essential for infection and constitutes a prime target for antiviral agents and vaccines. The pineapple-derived jacalin-related lectin AcmJRL is present in the medication bromelain in significant quantities and has previously been described to bind mannosides. Here, we performed a large ligand screening of AcmJRL by glycan array analysis, quantified the interaction with carbohydrates and validated high-mannose glycans as preferred ligands. Because the SARS-CoV-2 spike protein was previously reported to carry a high proportion of high-mannose N-glycans, we tested the binding of AcmJRL to the recombinantly produced extraviral domain of spike protein. We could demonstrate that AcmJRL binds the spike protein with a low-micromolar KD in a carbohydrate-dependent fashion.

Extract from Opuntia ficus-indica cladode delays the Aedes aegypti larval development by inducing an axenic midgut environment.

This study evaluated the effects of acute exposure of Aedes aegypti third instar (L3 ) larvae to the saline extract of Opuntia ficus-indica cladodes on the biological cycle and fertility of the emerging adults. For this, larvae were treated for 24 h with the extract at » LC50 (lethal concentration to kill 50% of larvae), ½ LC50 or LC50 ; the development and reproduction of the emerged adults were evaluated after a recovery period of 9 days. The resistance of proteins in the extract to hydrolysis by L3 digestive enzymes and histomorphological alterations in the larval midgut were also investigated. The extract contained lectin, flavonoids, cinnamic derivatives, terpenes, steroids, and reducing sugars. It showed a LC50 of 3.71% for 48 h. The data indicated mean survival times similar in control and extract treatments. It was observed development delay in extract-treated groups, with a lower number of adults than in control. However, the females that emerged laid similar number of eggs in control and treatments. Histological evaluation revealed absence of bacterial and fungal microorganisms in the food content in midguts from larvae treated with cladode extract. Electrophoresis revealed that three polypeptides in the extract resisted to hydrolysis by L3 digestive proteases for 90 min. The lectin activity was not altered even after 24-h incubation with the enzymes. In conclusion, the extract from O. ficus-indica can delay the development of Ae. aegypti larvae, which may be linked to induction of an axenic environment at larval midgut and permanence of lectin activity even after proteolysis.