Scientists explore natural lectin to cure COVID-19


Researchers from Friedrich-Alexander University Erlangen-Nürnberg-Germany and the University Hospital Tübingen-Germany along with experts from Marinomed Biotech AG-Austria are exploring the antiviral properties of a natural lectin from bread wheat (Triticum vulgaris) called Wheat Germ Agglutinin (WGA) to treat COVID-19.

Their study findings showed that the Wheat Germ Agglutinin (WGA) demonstrated antiviral properties not only against the original wildtype SARS-CoV-2 coronavirus but also against the Alpha and Beta variants as well.

To date several natural compounds have shown potential as antiviral substances and have the advantages of broad availabilities and large therapeutic windows.

The Austrian and German study team report that lectin from Triticum vulgaris (Wheat Germ Agglutinin) displays antiviral activity against SARS-CoV-2 and its major Variants of Concern (VoC), Alpha and Beta.

In the past, natural substances have been highlighted repeatedly for their antiviral potential against a variety of viruses. Since the outbreak of the current SARS-CoV-2 pandemic, several natural substances were tested for their potential effects against SARS-CoV-2. Among them, iota-carrageenan and quinine were shown to potently inhibit SARS-CoV-2 replication in vitro [36,37] and in the case of iota-carrageenan also in vivo [38].

Moreover, other natural compounds that are undergoing clinical trials were examined for their potential to treat COVID-19, for example, vitamin C or D, which were suggested to reduce the severity of cytokine storms [39,40], or lactoferrin, which was considered to compete with the virus in sialic acid binding [41].

A different mechanism was suggested for phytoestrogens and estrogens, which bind to the cell-surface Heat Shock Protein A5 responsible for pathogen entry and may therefore interfere with SARS-CoV-2 attachment [42]. Furthermore, natural substances such as resveratrol or melatonin were described as possible supplements in COVID-19 therapy due to their anti-inflammatory properties or their promising results against other viruses [43].

Numerous other classes of natural compounds considered to exhibit anti-SARS-CoV-2 activity via inhibition of viral interaction with cellular factors or inhibition of viral proteases are mentioned in several reviews [44,45]. Another class of naturally derived compounds that has been predicted as promising for the treatment of SARS-CoV-2 and other coronavirus infections is the group of lectins, which are proteins that bind specifically to carbohydrate structures [46].

Due to their potential to interact with viral envelope glycoproteins, different plant- and bacteria-derived lectins have been reported to exhibit strong antiviral activity against a number of viruses in the past, including SARS-CoV and MERS-CoV [47,48].

In addition to the antiviral properties of lectins, numerous studies have highlighted their potential as antineoplastic agents active against different tumor cell lines, and several clinical trials have been initiated [49,50].

A common lectin belonging to the group of chitin-binding lectins composed of hevein domains is lectin from Triticum vulgaris, also known as Wheat Germ Agglutinin (WGA) [51]. WGA is one of the most extensively studied and characterized lectins, which is widespread in nutrition. Up to 0.5 g/kg lectin concentration are present in wheat germ [52].

WGA binds specifically to N-Acetyl-D-glucosamine (GlcNAc) and was shown to interact with sialic acid residues [53]. Due to its binding profile, WGA is widely used to label cell membranes and tissues in scientific imaging [54,55], and was shown to detect specific Gram-positive and Gram-negative bacteria [56].

It expresses antifungal activity [57] and interacts with immune cells in several ways, such as inhibiting T lymphocyte proliferation [58,59]. In addition to that, several studies have highlighted the potential of WGA to improve drug delivery systems by using WGA-anchored nanoparticles to facilitate adhesion and uptake of therapeutics and enhance therapeutic efficacy [60,61].

By now, there is limited knowledge about its antiviral effects. WGA has been reported to inhibit the adsorption of human T-cell leukemia virus type 1 when added before adsorption [62]. However, anti-SARS-CoV-2 activity has not been analyzed yet.

Therefore, this study aimed to investigate of whether WGA is able to inhibit SARS-CoV-2 infection, and if so to evaluate its potential use as an antiviral agent in the current COVID-19 pandemic. Here, we report that WGA directly binds to SARS-CoV-2 and is able to inhibit infection of different human and non-human cell lines.

Furthermore, WGA exhibits antiviral activity against the SARS-CoV-2 VOCs Alpha and Beta in a human lung cell line, where it shows a therapeutic window of up to four log stages.

Due to its low cytotoxicity profile and its antiviral activity in the nanomolar range, our data could pave the way for a clinical evaluation of WGA as a prophylactic and therapeutic agent in COVID-19 infections.

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