Genetically modified seeds for inhibiting viral replication via the enhanced control (ACF) system with combined methods for treating or preventing viral diseases, and methods for preventing and eliminating pandemics

Abstract

An alternative method is disclosed for the prevention and treatment of diseases caused by viral pathogens of humans and animals, such as coronaviruses and influenza viruses, by adding or fortifying food with a food product or a part thereof obtained from the genetically modified plant of the present application. The method provides a seed of the genetically modified plant. wherein the genome of the seed comprises an exogenous recombinant polynucleotide encoding a combination of polypeptides that are carbohydrate binding proteins, in particular lectins that are combined in a manner to overcome potential toxicity caused by their transgenic expression in combination as disclosed herein, and that reduce the concentration of each of said carbohydrate binding proteins when expressed as part of a combination compared to the transgenic expression of any of said carbohydrate binding proteins individually, said seed exhibiting inhibition of viral replication and providing immunity against viral pathogens.

Description

[Technical field]

[0001] The present invention relates generally to agriculture, food, transgenic plant seeds and plants derived therefrom, and viral diseases, and more particularly to methods of treating or preventing viral diseases, including transgenic plant seeds to inhibit viral replication and provide immunity to viral pathogens, and foods produced from plants and plant parts obtained from said transgenic plant seeds. (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 305,137, filed January 31, 2022. [Background technology]

[0002] Infectious diseases are illnesses caused by pathogenic biological agents such as viruses, bacteria, fungi, parasites, and protozoa. Such diseases spread among people through contact with contaminated surfaces, body fluids, blood products, through the air, insect bites, and ingesting contaminated food and drink. While some infectious diseases can be treated or prevented by taking medicines or vaccines, there is growing awareness of healthy diet and food supplementation to help prevent and recover from these diseases. Nutrients not only play an important role in maintaining the normal physiological function and health of the human body, but they are also necessary to boost the immunity of the human body and are effective against viral infections. These nutrients exert their antiviral capabilities directly by entering the defense mechanism by interfering with the target virus, or indirectly by activating cells related to the adaptive immune system.

[0003] Viral infections are highly contagious and easily transmitted, and can even cause pandemics, such as the recent COVID-19, resulting in mass deaths around the world. While the most practical way to prevent viral infection is to practice self-hygiene and social distancing, boosting an individual's immunity by consuming appropriate foods with balanced nutrients is highly effective against viral infections. Foods containing vitamins, minerals, fatty acids, various polysaccharides, and some non-nutrients (such as polyphenols) have shown therapeutic effects on viral function.

[0004] Many viral infections are highly contagious and easily transmitted, causing large-scale health damage and even deaths worldwide. Recent viral infections include those caused by viruses such as measles, HIV, influenza, herpes simplex virus, dengue fever, chikungunya, Zika, and hepatitis. Several viruses that cause respiratory diseases have also emerged recently, such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). According to the CDC and WHO, the Spanish Flu, caused by the H1N1 influenza virus in the early 20th century, is one of the deadliest viruses in human history. The recent outbreak of COVID-19, caused by the novel coronavirus SARS-CoV-2 associated with the respiratory syndrome, was declared a pandemic by the WHO in March 2020.

[0005] The COVID-19 pandemic, also known as coronavirus pandemic, is the ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, despite the availability of a wide range of antiviral drugs that may be used in the process of finding an appropriate treatment, and the widespread availability of vaccines, the sudden emergence of novel viral strains and the resistance of viruses to such developed antiviral drugs and vaccines remain major challenges in the art, and there is also a need for sustainable, easily available, and mass-producible solutions that inhibit and target viral infection at its early stages, including the inhibition of viral replication and / or viral entry into individual hosts.

[0006] There has been great progress in the past few decades in the application of biotechnology to produce nutritionally improved food crops. New varieties of biofortified staple crops such as rice, maize, and wheat with essential micronutrients and genetically modified crops have the ability to fight chronic diseases. Thus, there is a need for genetically modified crops that can be used as food supplements and provide broad protection against viral pathogens such as measles virus, HIV, influenza, herpes simplex virus, dengue, chikungunya, Zika, and hepatitis. There is also a pressing need to address other viruses such as Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and SARS-CoV-2, the pathogen that caused the recent pandemic. The present invention aims to meet such needs and provides a solution to the problems highlighted above. Summary of the Invention

[0007] The present disclosure provides a genetically modified plant seed comprising an exogenous recombinant polynucleotide encoding a combination of carbohydrate binding proteins to inhibit viral replication and provide immunity to viral pathogens. Additionally, the present disclosure provides a method for treating or preventing a viral disease comprising administering to an individual in need thereof an effective amount of a food product derived from a plant or plant part obtained from the genetically modified plant seed comprising an exogenous recombinant polynucleotide encoding a combination of carbohydrate binding proteins to inhibit viral replication and provide immunity to viral pathogens.

[0008] In one aspect of the present invention, a genetically modified plant seed for inhibiting viral replication and providing immunity to viral pathogens is disclosed, wherein the genome of the seed comprises an exogenous recombinant polynucleotide encoding a combination of polypeptides, the polypeptides being carbohydrate binding proteins, and the seed exhibits inhibition of viral replication and provides immunity to viral pathogens.

[0009] In another aspect of the present invention, there is provided a genetically modified plant seed for inhibiting viral replication and providing immunity to viral pathogens as disclosed herein, wherein said genetically modified plant seed is sown in agricultural, horticultural and greenhouse methods to produce mass-produced plants and plant parts, said plant parts including grains, harvested seeds and by-products, said mass-produced plants and plant parts are processed to produce food products, said food products including bread, cereals, flour, baby food, snack food, pet food, dry soups, dry beverage mixes and textured vegetable protein, said by-products including bran, middlings, mill run, shorts, red dog, sieve, germ meal and germ oil, said by-products producing animal feed and fertilizer, said food products exhibiting inhibition of viral replication and providing immunity to viral pathogens.

[0010] In one aspect of the invention, a recombinant polynucleotide encoding a combination of polypeptides is disclosed, wherein the polypeptides are glycoproteins, wherein the glycoprotein binding proteins are encoded by a recombinant polynucleotide encoding the combination of polypeptides, the recombinant polynucleotide encoding the combination of polypeptides is under the control of a promoter selected from a heterologous and a homologous promoter, the promoter provides ubiquitous expression or targeted expression at a specific site in the plant from the recombinant polynucleotide encoding the combination of polypeptides, the promoter functions in a plant cell and is operably linked to a coding sequence of the recombinant polynucleotide encoding the combination of polypeptides, and wherein expression of the recombinant polynucleotide encoding the combination of polypeptides results in a combination of polypeptides selected from the group consisting of two different glycoprotein combinations, expression of the exogenous recombinant polynucleotide encoding the combination of polypeptides results in a combination of polypeptides selected from the group consisting of three different glycoprotein combinations, expression of the exogenous recombinant polynucleotide encoding the combination of polypeptides results in a combination of polypeptides selected from the group consisting of four different glycoprotein combinations, and expression of the exogenous recombinant polynucleotide encoding the combination of polypeptides results in a combination of polypeptides selected from the group consisting of five different glycoprotein combinations. Four different sugar-binding proteins encoding a combination of polypeptides expressed from an exogenous recombinant polynucleotide, and five different sugar-binding proteins encoding a combination of polypeptides expressed from an exogenous recombinant polynucleotide, where the sugar-binding proteins include mannose-specific plant lectin, N-acetylglucosamine-specific plant lectin, glucose-specific plant lectin, galactose-specific plant lectin, N-acetylgalactosamine-specific plant lectin, galactose-specific plant agglutinin, N-acetylgalactosamine-specific plant agglutinin, glucose-specific plant agglutinin, and N-acetylglucosamine-specific plant agglutinin.

[0011] In one aspect of the present invention, a method for treating or preventing a viral disease is disclosed, comprising administering to an individual in need an effective amount of a plant obtained from a seed of a genetically modified plant and a food product produced from a part of the plant, comprising the steps of: (a) producing a recombinant polynucleotide encoding a combination of polypeptides, wherein said polypeptide is a sugar-binding protein, wherein said sugar-binding protein is encoded by a recombinant polynucleotide encoding a combination of polypeptides, wherein said recombinant polynucleotide encoding a combination of polypeptides is selected from a heterologous and a homologous promoter, wherein said promoter confers ubiquitous expression or plant part-specific targeted expression from the recombinant polynucleotide encoding the combination of polypeptides, wherein said promoter functions in a plant cell and is operably linked to a coding sequence of the recombinant polynucleotide encoding the combination of polypeptides. (b) transforming a plant cell by introducing the recombinant polynucleotide of step (a) and regenerating from said cell a fully fertile transformed plant in vitro, wherein the transformed plant expresses a combination of polypeptides, wherein said polypeptides are sugar-binding proteins. (c) cultivating the genetically modified plant to obtain seeds of said plant. (d) sowing seeds of said genetically modified plants to produce genetically modified plants and parts of plants for mass production by agriculture, horticulture or greenhouse cultivation. (e) processing genetically modified plants and plant parts to obtain food products, wherein the food products exhibit an inhibitory effect on viral replication and provide immunity to viral pathogens, wherein the plant parts consist of grains, harvested seeds, and by-products, and wherein the mass-produced plants and plant parts are processed to obtain food products, wherein the food products consist of bread, cereals, flour, baby food, snack foods, pet food, dry soups, dry beverage mixes, and processed vegetable proteins, wherein the by-products consist of bran, middle rings, mill run, short, red dog, screening, germ meal, germ oil, wherein the by-products produce animal feed and fertilizer, and wherein administration of an effective amount of the food product to an individual in need leads to a reduction or elimination of sites of viral latency in the individual, wherein the sites of viral latency include viral deposits in the intestine and central nervous system (CNS) of the individual.

[0012] It is already an established fact that the combination of carbohydrate-binding proteins, especially lectins, inhibits viral transcription. Lectins have a strong antiviral effect, which is believed to be because they directly bind to the viral envelope glycans and prevent the virus from entering cells. Therefore, according to the present invention, foods derived from genetically modified corn and wheat formed by combining lectins from multiple sources can help boost immunity against viral pathogens such as coronaviruses and influenza viruses. Furthermore, mass production of such genetically modified seeds and their application in food supply could potentially eradicate SARS-CoV-2 and influenza viruses in a demographic-based manner.

[0013] Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and specific examples, while indicating specific embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. [Brief description of the drawings]

[0014] The accompanying drawings are included to provide a further understanding of the invention, are incorporated in and constitute a part of the invention, and together with the specification, serve to explain the principles of the invention. [Figure 1] Schematic diagram of the production of transgenic plants: a) construct a recombinant polynucleotide transgenic construct consisting of a combination of sugar-binding proteins for expression in a plant, where n represents the number of sugar-binding protein genes simultaneously integrated into the construct; this construct is then used in (b) to transform a plant cell, for example using an Agrobacterium intermediate method, leading to the regeneration of a transgenic plant; and then confirm that a particular sugar-binding protein combination shows the desired expression (at the desired concentration), as required empirically and tested as an embodiment of the present disclosure, to produce transgenic plant seeds according to the present disclosure. [Diagram 2] FIG. 1 is a schematic diagram of carbohydrate-binding proteins such as lectin defense against viral pathogens, where the combination of lectins is extracted and produced from the seeds of genetically modified plants or food derived therefrom, as shown in FIG. 1 as an embodiment of the present disclosure, and the underlying mechanisms of the present disclosure include: (a) inhibiting nuclear entry and thereby inhibiting viral pathogen replication; (b) causing viral pathogen aggregation, which allows for elimination via various host mechanisms; and (c) preventing early viral pathogen entry into host cells by binding to viral pathogen surface proteins and preventing interaction with host cell receptors, where mechanisms (a) to (c) work in concert to neutralize early viral pathogens, thereby inhibiting or preventing viral pathogen latency site formation, and thus suppressing viral pathogen mutations and the emergence of viral strains resistant to other antivirals and vaccines. Also, (d) shows in vivo protection applicable to the host in a mouse model. [Diagram 3]Schematic diagram of an in vitro toxicity and cell viability assay, in which cells are experimentally assayed with (a) an experimental combination of lectins of the present disclosure, (b) the individual lectins forming said combination, (c) a control protein not known to have a protective effect against viral pathogens, and (d) untreated Vero E6 cells to determine toxicity and resistance upon such exposure and treatment, in which the protein combination or individual proteins can be obtained directly from the original plant source and combined at desired concentrations to match the same concentrations extracted from the experimentally produced transgenic plants and transgenic plant seeds of Example 1 disclosed herein. [Figure 4] Schematic diagram of an in vitro assay, comparing (a) experimental combinations of lectins, (b) individual lectins forming said combinations, (c) control proteins not known to have protective effects against viral pathogens, and (d) untreated Vero E6 cells to experimentally assay and determine protection from viral pathogens such as influenza virus, SARS-CoV-2, feline infectious peritonitis virus, etc., in Vero E6 cells, where the protein combinations or individual proteins can be sourced directly from original plant sources and combined at desired concentrations to match the same concentrations extracted from the experimentally produced transgenic plants and transgenic plant seeds of Example 1 disclosed herein. [Diagram 5]1 is a schematic diagram of the in vivo antiviral activity of mice fed pellets of food containing the desired experimental concentrations of experimental combinations of lectins of the present disclosure (a) and (e), compared to the individual lectins that make up the combinations (b) and (f), and compared to control proteins (c) and (g) that are not known to have a protective effect against viral pathogens. A control protein not known to have a protective effect against viral pathogens, and (d) and (h) non-treated mice are experimentally assayed to determine the antiviral activity of such treatments to determine protection from viral pathogens and infections by pathogens such as influenza virus, SARS-CoV-2, feline infectious peritonitis infection, and (I) infections based on direct exposure to viral pathogens, and (II) infections in mouse models identified as contact-based transmission of infection from already infected mice to unexposed mice, and (II) transmission of infection by contact from already infected mice to uninfected mice, where the protein combinations or individual proteins can be sourced directly from the original plant source and combined at the desired concentrations to match the concentrations extracted from the experimentally produced transgenic plants and transgenic plant seeds of Example 1 disclosed herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] The present invention can be more readily understood by reference to the following detailed description, taken in conjunction with the accompanying drawings, which form a part of this disclosure. It is to be understood that the present invention is not limited to the specific devices, pharmaceuticals, systems, conditions or parameters described and / or shown herein, and that the terms used herein are for illustrative purposes only and are not intended to limit the invention as claimed. Also, as used in the specification, including the appended claims, the singular forms "a", "an" and "the" include the plural, and reference to a particular numerical value includes at least that particular value, unless the content clearly dictates otherwise. A range may be expressed herein as being "about" or "approximately" from another particular value. When such a range is expressed, it is another embodiment. It is also to be understood that, unless otherwise specified, the dimensions and material properties described herein are exemplary and not limiting, and are described for a better understanding of suitable practical examples, and that variations outside the range of the values ​​described may be within the scope of the invention, depending on the particular application.

[0016] The terms "comprising," "having," "including," and "containing" are to be construed as open-ended terms (i.e., meaning "including, but not limited to," permitting the presence of one or more features or components) unless otherwise noted. Although various embodiments are described herein in terms of "comprising," it should be understood that under various circumstances, the relevant embodiment may also be described in terms of "consisting of" or "consisting essentially of."

[0017] As such, the terms "a" (or "an"), "one or more," and "at least one" may be used interchangeably herein. Furthermore, "and / or" as used herein is to be construed as a specific disclosure of each of the two specified features or components with or without the other. Furthermore, unless otherwise stated or clear from the context, the term "or" as used herein is to be understood as being inclusive. Additionally, unless otherwise stated or clear from the context, the terms "a," "an," and "the" as used herein are to be construed as singular or plural.

[0018] Also, when describing a range of values, it should be understood that the described property may be an individual value included within the range. For example, the phrase "about pH 4 to about pH 6" may include, but is not limited to, pH 4, 4.2, 4.6, 5.1, 5.5, etc., and any value therebetween. Furthermore, the phrase "about pH 4 to about pH 6" does not mean that the pH of the formulation in question varies from pH 4 to pH 6 by 2 pH units during storage, but means that the pH value of the solution is selected from the range and the pH is buffered around that pH. In some embodiments, when the terms "about" and "approximately" are used, they mean the stated numerical value plus or minus 10%.

[0019] As used herein, the terms "transgenic plant seeds," "transgenic plant," and "transgenic plant parts" refer to plants, seeds, or plant cells whose genomes have been modified by the incorporation of exogenous genetic material, such as by transformation as described herein. The term "transgenic plant" is used to refer to the plants produced from an initial transformation event, or to the progeny of subsequent generations, or to progeny produced from the crossing of such transformed plants, so long as the exogenous genetic material remains integrated into the genome.

[0020] As used herein, the term "exogenous" or "foreign" means that a nucleic acid molecule, e.g., a recombinant polynucleotide, originates from outside the plant into which it is introduced. An exogenous nucleic acid molecule may be composed of naturally occurring or non-naturally occurring polynucleotides and may originate from any organism, including the same or a different plant species as that into which it is being introduced.

[0021] As used herein, the term "recombinant polynucleotide" refers to a polynucleotide that has genetically engineered modifications introduced by manipulation via mutagenesis, restriction enzymes, and the like. Recombinant polynucleotides can be composed of DNA segments obtained from different sources, or DNA segments obtained from the same source that have been engineered to join in a manner that does not occur in nature. Recombinant polynucleotides can exist extracellularly, for example as PCR fragments, or can be integrated into a genome, such as a plant genome.

[0022] As used herein, a "functional portion" of the encoding region of a polypeptide provided herein is a portion of the encoding region sufficient to provide a desired activity. Where expression of a protein is desired, the functional portion generally comprises the entire coding region of the polypeptide, although specific deletions, truncations, rearrangements, etc. of the polypeptide may also maintain the desired activity, or in some cases, improve the activity. Those skilled in the art will know how to screen for such desired modifications, and such polypeptides are considered to be within the scope of the present invention. Where gene suppression methods are used, smaller portions of the coding region may be used to achieve the desired effect.

[0023] As used herein, a "control plant" or "subject plant" is a plant used to identify enhanced phenotypes in a transgenic plant grown from a transgenic seed provided herein. A control plant may optionally be a transgenic plant line that consists of an empty vector or marker gene but does not contain the recombinant polynucleotide of the present application that is expressed in the transgenic plant being evaluated. Generally, a control plant is a plant of the same line or variety as the transgenic plant being tested.

[0024] The term "expression" as used herein refers to the transcription of DNA to produce RNA. The resulting RNA may be, but is not limited to, an mRNA encoding a protein, an antisense RNA complementary to an mRNA encoding a protein, or an RNA transcript consisting of a combination of sense and antisense gene regions for use in RNAi technology. The term "encoding" as used herein further refers to the production of an encoded protein from an mRNA.

[0025] As used herein, the terms "foodstuff", "food", and "food supplement" are used interchangeably and refer to and include bread, cereal, flour, baby food, snack food, pet food, dried soup, dried beverage mixes, and animal feed derived from the genetically modified plant by-products obtained from the seeds of the genetically modified plants disclosed herein.

[0026] As used herein, the term "food / seed anti-communicable fortification system (ACF)" means an ACF consisting of genetically modified plant seeds, plants and plant parts prepared and obtained from the genetically modified plant seeds, and foods produced and obtained therefrom, where the seeds, plants, plant parts, and foods inhibit viral replication and provide immunity against viral pathogens.

[0027] As used in this document, the term “enhanced control systems (ACF) for agricultural spaces” refers to ACFs that protect agricultural spaces from harmful pathogens and includes ACFs that are specific to the agricultural feed market.

[0028] As used herein, the term "viral disease" means and includes the symptoms, etiology, and symptoms resulting from a viral infection and the various stages and symptoms of a viral disease caused by exposure to a viral pathogen.

[0029] As used herein, the term "effective amount" refers to the amount of a drug, composition, or food or dietary supplement disclosed herein required to prevent or ameliorate / treat symptoms of disease associated with an untreated individual exposed or likely to be exposed to a viral pathogen, which then provides or enhances immunity against such viral pathogen. The effective amount of an active compound or composition used in practicing the present invention for the prevention or treatment of disease will vary depending on the method of administration, the age, weight, and health of the subject. Ultimately, the attending physician, nutritionist, or veterinarian will determine the appropriate amount and administration schedule, and such amount will be referred to as an "effective amount."

[0030] As used herein, the terms "prevent," "preventing," "prevention," and the like refer to measures to reduce the likelihood of contracting a disease or condition caused by a viral pathogen, particularly as disclosed herein. It is understood that preventing a disease, disorder, or condition does not necessarily mean completely avoiding (but does not mean eliminating) the disorder, condition, or symptom associated therewith, but may also mean making it less severe, within the definition. That is, prevention may be complete or partial.

[0031] As used herein, the terms "treat," "treating," "treatment," and the like refer to reducing or ameliorating a disease, disorder, or condition caused by a viral pathogen, particularly as disclosed herein. It is understood that treating a disorder or condition does not require (but does not eliminate) the complete elimination of the disorder, condition, or symptoms associated therewith. That is, treatment may be complete or partial.

[0032] As used herein, the terms "slate," "slate system," and "slate system for the anti-communicable fortification system (ACF) of foodstuffs / seeds" refer to and include a ready-made structure that envisions additional genetic sequences being added to the ACF to create a dynamic and flexible system against future diseases and pandemics of unknown importance and impact. Such a slate system may be employed to modify and add sequences encoding other polypeptides to enhance human protection in addition to or in combination with developing a systematic plan against ACF.

[0033] In any range described herein, the endpoints of the range are included within the range. However, the description also contemplates the same ranges with the lower and / or upper limits excluded. Additional features and variations of the present invention will be apparent to one of ordinary skill in the art from the entirety of this application, including the drawings and detailed description, and all such features are intended as aspects of the present invention. Similarly, features of the invention described herein can be recombined into additional embodiments that are intended as aspects of the invention, regardless of whether such combinations are specifically mentioned above as features or embodiments of the invention. Moreover, only limitations described herein as essential to the invention should be considered as such limitations. Variations of the invention that lack reductions not described herein as essential are intended as aspects of the invention.

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood among those of ordinary skill in the art to which this disclosure pertains. Units, prefixes, and symbols are written in the format accepted by the International System of Units (SI). Numerical ranges are inclusive of the numbers defining the range. Unless otherwise indicated, amino acid sequences are written from left to right from the amino group side to the carboxyl group side. The headings provided herein are not limitations of the various aspects of this disclosure. The various aspects of this disclosure can be obtained by reference to the entire specification. This entire document is intended to be viewed as a unified disclosure, and it is understood that all combinations of features described herein are contemplated. All references cited herein are incorporated by reference in their entirety into this disclosure.

[0035] Hereinafter, the embodiments will be described in detail with reference to the accompanying drawings. In order to avoid unnecessary obscuration in the present disclosure, well-known features may not be described. Or, for example, substantially identical elements may not be described redundantly. This is for ease of understanding. The drawings and the following description are provided to enable those skilled in the art to fully understand the present disclosure, and are not intended to limit the scope of the present disclosure defined in the appended claims.

[0036] Whenever a definition of a variable herein recites a list of chemical groups, it is intended that the definition of that variable includes any one or combination of the listed groups. The recitation of an embodiment for a variable or aspect herein includes that embodiment as a single embodiment or in combination with other embodiments or portions thereof.

[0037] Any food product, genetically modified plant seed, genetically modified plant and plant part thereof, recombinant polynucleotide, polypeptide, sugar-binding protein, lectin, or method described herein can be combined with one or more of any other compositions and methods described herein.

[0038] As mentioned above, coronaviruses, rhabdoviruses, influenza viruses, dengue viruses, severe acute respiratory syndrome coronavirus (SARS-CoV), severe acute respiratory syndrome coronavirus 1 (SARS-CoV1), severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), Middle East respiratory syndrome coronavirus (MERS-CoV), orthomyxoviruses, hepatitis viruses, hepatitis C virus (HCV), hepatitis E virus (HEV), Ebola virus, polio virus, measles virus, , retrovirus, adult human T-cell leukemia virus (HTLV-1), virus (MERS-CoV), orthomyxovirus, hepatitis virus, hepatitis C virus (HCV), hepatitis E virus (HEV), Ebola virus, polio and measles virus, retrovirus, adult T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus (HIV), norovirus, cold virus, West Nile virus, rabies virus, poliovirus, mumps virus, measles virus, The continuing problem of infectious and transmissible diseases caused by viral pathogens such as Chikungunya virus, Zika virus, Herpes simplex virus, HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1, Feline infectious peritonitis virus (FIPV), Feline enteric coronavirus (FECV), Rinderpest virus, Foot and mouth disease virus (FMDV), Cypovirus (CPV), and Reovirus poses a need for alternative prevention and treatment strategies and mechanisms. Existing antiviral drugs, vaccines, and other pharmacological measures are inadequate and fail to address the public health needs of managing infectious viral diseases and preventing their spread due to the sudden emergence of new viral strains, viral mutations resulting in resistance to antivirals and vaccines, and the need for alternative treatment strategies and mechanisms. What is urgently needed are sustainable, accessible and mass-produced alternatives and methods that can inhibit viral replication and entry into individual hosts at the early stages of viral infection, block and inhibit viral infection, contain and prevent viral diseases, and boost immunity against viral pathogens.

[0039] To address the problems and needs of viral epidemics as mentioned above, the present disclosure provides an alternative solution in the form of food products or food supplements or fortifications derived from the genetically modified plants disclosed herein, obtained from the genetically modified plants disclosed herein or parts thereof, capable of preventing, combating, and even treating acute and chronic viral diseases of viral epidemics that may develop into pandemics such as the recently emerged COVID-19 pandemic. Such foods can be easily incorporated into the diets of people around the world and can also be used to complement and substantiate antiviral agents, vaccines, and other pharmacological means and methods, particularly by reducing or eliminating sites of incubation in individuals who are or may be exposed to such viral pathogens. Sites of incubation often include the gut and central nervous system (CNS) of such individuals, which may be humans or animals that ingest the foods produced and disclosed according to the present disclosure.

[0040] The objective of the present invention is to provide a set of proteins that can be used alone or in combination to produce genetically modified maize and / or genetically modified wheat that can inhibit the replication of viral pathogens such as SARS-CoV-2, influenza virus, etc. In other words, genetically modified plants such as genetically modified maize and genetically modified wheat produced with the specific polypeptides disclosed in the present invention can be mass-produced in the form of bread and other foods as fortified foods for human and animal consumption and utilized to confer broad protection against viral pathogens.

[0041] It is already an established fact in the field that lectin combinations inhibit viral transcription. Lectins have strong antiviral properties because they directly bind to viral envelope glycans, preventing the virus from entering cells. The efficacy of lectins has been shown in several research studies. Table 1 below lists some examples of previous and published studies that have shown promise in inhibiting the viral pathogen SARS-CoV-2, the cause of the COVID-19 pandemic:

[0042] (Table 1) Carbohydrate-binding proteins known to block viral infection [Table 1]

[0043] It has also been shown that these lectins may inhibit influenza and significantly reduce morbidity and mortality from endemic influenza worldwide.

[0044] Therefore, according to the present invention, genetically modified maize and wheat formed by combining lectins from multiple sources can help to boost immunity against coronaviruses. Furthermore, such genetically modified seeds can be mass-produced and applied to the food supply, potentially eradicating viral pathogens in a population-based manner.

[0045] Also, genetically modified plants and crops can be transformed with recombinant polynucleotides encoding the above-mentioned combinations of lectin proteins by any in vivo method or combination of established techniques and / or methods known to those skilled in the art without changing the spirit of the present invention. Established techniques for plant culture have rapidly increased the availability of raw materials by using appropriate regeneration and propagation systems. The novelty of this invention is the use of the above-mentioned lectins in a specific combination. Thus, genetically modified seeds produced with the above-mentioned combinations of lectins can be mass-produced for application in the food supply. Such mass-produced seeds could be utilized to make bread and other staple food products that protect against various viral pathogens, including SARS-CoV-2. That is, the present invention provides a novel and safe food supplement that may reduce or completely eliminate sites of latency, such as the gut and central nervous system (CNS), in users who consume foods produced according to the above-mentioned methods. In combination with pharmacology, they may also be an adjunct to the prevention and treatment of viral diseases such as COVID-19 and pandemic influenza, reducing or eliminating the viral load and reservoir in the host, denying viral pathogens the opportunity to replicate, mutate, and generate resistant viral strains.

[0046] In one embodiment of the present invention, a genetically modified plant seed is disclosed that inhibits viral replication and provides immunity to viral pathogens, the genome of the seed is comprised of an exogenous recombinant polynucleotide that encodes a combination of polypeptides, the polypeptides being glyco-binding proteins, and the seed inhibits viral replication and provides immunity to viral pathogens.

[0047] In another embodiment of the genetically modified plant seed disclosed herein, the polypeptides in the combination of polypeptides are sugar-binding proteins, and the combination of polypeptides is selected from the group consisting of two different sugar-binding protein combinations for expression from an exogenous recombinant polynucleotide encoding the combination of polypeptides, three different sugar-binding proteins for expression from an exogenous recombinant polynucleotide encoding the combination of polypeptides, four different sugar-binding proteins for expression from an exogenous recombinant polynucleotide encoding the combination of polypeptides, and five different sugar-binding proteins for expression from an exogenous recombinant polynucleotide encoding the combination of polypeptides.

[0048] In another embodiment of the genetically modified plant seed disclosed herein, the combination of polypeptides is a combination of sugar-binding proteins encoded by an exogenous recombinant polynucleotide encoding the combination of polypeptides, and the exogenous recombinant polynucleotide encoding the combination of polypeptides is selected from a heterologous and a homologous promoter, the promoter providing broad range expression or plant part specific target expression from the exogenous recombinant polynucleotide encoding the combination of polypeptides, the promoter functioning in a plant cell and being operably linked to the coding sequence of the recombinant polynucleotide encoding the combination of polypeptides.

[0049] In another embodiment of the genetically modified plant seed disclosed herein, the combination of polypeptides is a combination of glyco-binding proteins that overcome potential toxicity resulting from the genetically modified plant seed or a plant grown from said seed, and are linked in a manner that reduces the concentration of each glyco-binding protein when expressed as part of the combination of glyco-binding proteins in the combination compared to the genetically modified plant seed or a plant grown from said seed of any one of the glyco-binding proteins in the genetically modified plant seed or a plant grown from said seed, and the concentration of each glyco-binding protein in the combination is between 1 milligram / milliliter (1 mg / ml) and 1 attogram / milliliter (1 ag / ml), typically in the typical range of 50 microgram / milliliter (50 μg / ml) and 1 picogram / milliliter (1 pg / ml). Highly active proteins and / or peptide sequences may have activity up to 1-10 ag / mL or 1-10 attogram / mL (attomolar concentrations).

[0050] In another embodiment of the genetically modified plant seeds disclosed herein, the carbohydrate-binding protein comprises a mannose-specific plant lectin, an N-acetylglucosamine-specific plant lectin, a glucose-specific plant lectin, a galactose-specific plant lectin, an N-acetylgalactosamine-specific plant agglutinin, an N-acetylgalactosamine-specific plant agglutinin, a glucose-specific plant agglutinin, or an N-acetylglucosamine-specific plant agglutinin.

[0051] In another embodiment of the genetically modified plant seeds disclosed herein, the sugar-binding proteins are lectins obtained from multiple sources, including glucose / mannose lectin or Dolichos lablab lectin 1 (DLL-I) from Lablab bean or Lablab purpureus, GlcNAc-specific agglutinin from tobacco or Nicotiana sp., mannose-specific agglutinin from Welsh onion or Allium sp., Galanthus sp.mannose-specific agglutinin from Lotus japonicus rhizome, chitin-specific lectin from Lycoris rhizome, Serpula vermicularis lectin (SVL), mannose-specific agglutinin from Amaryllis or Amaryllis, mannose-specific agglutinin from Galanthus nivalis or Snowdrop, mannose-specific agglutinin from Narcissus pseudonarcissus or Daffodil, mannose-specific agglutinin from Lycoris radiata or Spider lily, mannose-specific agglutinin from Chinese chive, mannose-specific agglutinin from Allium ursinum or Ramson, mannose-specific agglutinin from Colocasia esculenta or Taro, mannose-specific agglutinin from Cymbidium hybrids or Cymbidium orchid, mannose-specific agglutinin from Listera ovata, or Tsey blade, Epipactis Mannose-specific agglutinin from helleborine or broadleaf helleborine, Mannose-specific agglutinin from tulip hybrid or tulip, Mannose-specific agglutinin from Morus Nigra or black viburnum, GlcNAc-specific agglutinin from Phragmites australis or reed, GlcNAc-specific agglutinin from Nicotiana tabacum or tobacco, (GlcNAc)n-specific agglutinin from Urtica dioica or nettle, (GlcNAc)n-specific agglutinin from Hevea brasiliensis or rubber tree, GalNAc-specific agglutinin from Polygonatum multiflorum tetramer or Solomon's seal, GalNAc-specific agglutinin from Bryonia dioica or white bryony, GalNAc-specific agglutinin from Glechoma hederacea or ground ivy, Gal-specific agglutinin from Morus Nigra or black mulberry tree, Gal-specific agglutinin from Artocarpus integrifolia or jackfruit, Sambucus Neu5Acα from elderberry or elderberry (2.6) Gal / GalNAc specific agglutinins, Man / Glc specific agglutinins from Cladastris lutea or Yellowwood, Gal / GalNAc specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Viscum album or Mistletoe, GalNAcα(1,3)Gal > GalNAc > Gal specific agglutinins from Iris hybrids or Iris, Man / GalNAc specific agglutinins from Tulipa hybrids or Tulip, Hippeastrum hybrid agglutinins (HHA), Galanthus nivalis agglutinins (GNA), Cymbidium species agglutinins (CA), Urtica dioica agglutinins (UDA), cytovillin (SVN) isolated from Scytonema varium, sea coral (Gerardia savaglia), griffithsin from Griffithsia sp., or actinohibin from Longisporum albida.

[0052] In another embodiment of the genetically modified plant seeds disclosed herein, the viral pathogen includes a coronavirus, a rhabdovirus, an influenza virus, a dengue virus, a severe acute respiratory syndrome coronavirus (SARS-CoV), a severe acute respiratory syndrome coronavirus 1 (SARS-CoV1), a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), a Middle East respiratory syndrome coronavirus (MERS-CoV), an orthomyxovirus, a hepatitis virus, a hepatitis C virus (HCV), a hepatitis E virus (HEV), an Ebola virus, a polio measles virus, a retrovirus, an adult human T-cell leukemia virus type 1 (HTLV-1), a human immunodeficiency virus (HIV), a norovirus, a common cold virus, a West Nile virus, a rabies virus, a polio virus, a mumps virus, a measles virus, a chikungunya virus, These include Zika virus, herpes simplex virus, HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1, feline infectious peritonitis virus (FIPV), feline enteric coronavirus (FECV), rinderpest virus, foot-and-mouth disease virus (FMDV), cypovirus (CPV), and reovirus.

[0053] In another embodiment of the genetically modified plant seeds disclosed herein, the genetically modified plant seeds produce plants and plant parts that inhibit viral replication and provide immunity to viral pathogens, including corn, wheat, millet, rye, oats, barley, sorghum, rice, legumes, nuts, and tubers.

[0054] In another embodiment of the genetically modified plant seeds disclosed herein, the genetically modified plant seeds are sown to produce plants and plant parts for mass production through agriculture, horticulture, and greenhouse cultivation, wherein the plant parts consist of grains, harvested seeds, and by-products, wherein the mass produced plants and plant parts are processed to produce food products, wherein the food products consist of bread, cereals, flour, baby food, snack foods, pet food, dry soups, dry beverage mixes, and vegetable proteins, wherein the by-products consist of bran, middlings, mill run, short, red dog, screenings, germ flour, and germ oil, wherein the by-products produce animal feed and fertilizer, wherein the food products exhibit inhibition of viral replication and provide immunity against viral pathogens.

[0055] Part of this disclosure relates to the slate system of food / seed fortification systems (ACF) disclosed herein, where the lectins, lectin peptide fragments, or other combinations of novel artificial intelligence (AI) derived sequences derived from lectins and other antiviral peptide data can be used to update the original transgenic seed as needed against future pandemic agents and all known pathogens of clinical concern. Thus, in another embodiment of the transgenic plant seed disclosed herein, the polypeptide in the combination of polypeptides is a sugar-binding protein, where the sugar-binding protein comprises any other combination of artificial intelligence (AI) derived novel sequences derived from lectins, lectin peptide fragments, or any other combination of artificial intelligence (AI) derived novel sequences derived from lectins and other antiviral peptides, where the seed exhibits inhibition of viral replication and is immune to viral pathogens, where the viral pathogens include all known and unknown pathogens of clinical concern. Thus, in another embodiment of the genetically modified plant seed disclosed herein, the polypeptide in the combination of polypeptides is a sugar-binding protein, and the sugar-binding protein includes any other rational or artificial intelligence (AI) derived lectin lectin, lectin peptide fragment, or any other combination of artificial intelligence (AI) derived novel sequences derived from lectins and other antiviral peptides, where the seed exhibits inhibition of viral replication and is immune to viral pathogens, where viral pathogens include all known and unknown pathogens of clinical concern. Thus, the present disclosure in this aspect and embodiment addresses the future need for upgrading genetically modified plant seeds, or the need for new genetically modified plant seeds available in the case of resistance to viral pathogens, or the need for new pathogen coverage. A "slate" of new rational combinations can be added to the original genetically modified seed based on the present disclosure.

[0056] In one embodiment of the present invention, a recombinant polynucleotide encoding a combination of polypeptides is disclosed, wherein the polypeptides are sugar-binding proteins, the sugar-binding proteins are encoded by a recombinant polynucleotide encoding the combination of polypeptides, the recombinant polynucleotide encoding the combination of polypeptides is under the control of a promoter selected from a heterologous and a homologous promoter, the promoter provides ubiquitous expression or plant site-specific targeted expression from the recombinant polynucleotide encoding the combination of polypeptides, the promoter functions in a plant cell and is operably linked to a coding sequence of the recombinant polynucleotide encoding the combination of polypeptides, the combination of polypeptides is selected from the group consisting of two different sugar-binding protein combinations for expression from a recombinant polynucleotide encoding an exogenous combination of polypeptides, selected from the group consisting of three different sugar-binding protein combinations for expression from a recombinant polynucleotide encoding an exogenous combination of polypeptides, selected from the group consisting of four different sugar-binding proteins for expression from an exogenous recombinant polynucleotide encoding a combination of polypeptides, and selected from the group consisting of five different sugar-binding proteins for expression from an exogenous recombinant polynucleotide encoding a combination of polypeptides, wherein the sugar-binding proteins are selected from the group consisting of mannose-specific plant lectin, N-acetylglucosamine, ... They consist of glucose-specific plant lectins, galactose-specific plant lectins, N-acetylgalactosamine-specific plant lectins, galactose-specific plant agglutinins, N-acetylgalactosamine-specific plant agglutinins, glucose-specific plant agglutinins, and N-acetylglucosamine-specific plant agglutinins.

[0057] In another embodiment of the recombinant polynucleotide encoding a combination of polypeptides disclosed herein, the sugar-binding proteins are lectins obtained from multiple sources, including glucose / mannose lectin from Lablab bean or Lablab purpureus or Dolichos lablab lectin 1 (DLL-I), GlcNAc-specific agglutinin from tobacco or Nicotiana sp., mannose-specific agglutinin from Welsh onion or Allium sp., Galanthus sp.mannose-specific agglutinin from Lotus japonicus rhizome, chitin-specific lectin from Lycoris rhizome, Serpula vermicularis lectin (SVL), mannose-specific agglutinin from Amaryllis or Amaryllis, mannose-specific agglutinin from Galanthus nivalis or Snowdrop, mannose-specific agglutinin from Narcissus pseudonarcissus or Daffodil, mannose-specific agglutinin from Lycoris radiata or Spider lily, mannose-specific agglutinin from Chinese chive, mannose-specific agglutinin from Allium ursinum or Ramson, mannose-specific agglutinin from Colocasia esculenta or Taro, mannose-specific agglutinin from Cymbidium hybrids or Cymbidium orchid, mannose-specific agglutinin from Listera ovata, or Tsey blade, Epipactis Mannose-specific agglutinin from helleborine or broadleaf helleborine, Mannose-specific agglutinin from tulip hybrid or tulip, Mannose-specific agglutinin from Morus Nigra or black viburnum, GlcNAc-specific agglutinin from Phragmites australis or reed, GlcNAc-specific agglutinin from Nicotiana tabacum or tobacco, (GlcNAc)n-specific agglutinin from Urtica dioica or nettle, (GlcNAc)n-specific agglutinin from Hevea brasiliensis or rubber tree, GalNAc-specific agglutinin from Polygonatum multiflorum tetramer or Solomon's seal, GalNAc-specific agglutinin from Bryonia dioica or white bryony, GalNAc-specific agglutinin from Glechoma hederacea or ground ivy, Gal-specific agglutinin from Morus Nigra or black mulberry tree, Gal-specific agglutinin from Artocarpus integrifolia or jackfruit, Sambucus Neu5Acα from elderberry or elderberry (2.6) Gal / GalNAc specific agglutinins, Man / Glc specific agglutinins from Cladastris lutea or Yellowwood, Gal / GalNAc specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Viscum album or Mistletoe, GalNAcα(1,3)Gal > GalNAc > Gal specific agglutinins from Iris hybrids or Iris, Man / GalNAc specific agglutinins from Tulipa hybrids or Tulip, Hippeastrum hybrid agglutinins (HHA), Galanthus nivalis agglutinins (GNA), Cymbidium species agglutinins (CA), Urtica dioica agglutinins (UDA), cytovillin (SVN) isolated from Scytonema varium, sea coral (Gerardia savaglia), griffithsin from Griffithsia sp., or actinohibin from Longisporum albida.

[0058] In another embodiment of the recombinant polynucleotide encoding the polypeptide combination disclosed herein, the polypeptide in the polypeptide combination is a carbohydrate binding protein, the carbohydrate binding protein comprising a lectin, a lectin peptide fragment, or any other rational combination of artificial intelligence (AI) derived novel sequences derived from lectins and other antiviral peptides, wherein the seeds exhibit inhibition of viral replication and provide immunity against viral pathogens, wherein viral pathogens include all known and unknown pathogens of clinical concern.

[0059] In one embodiment of the present invention, a method for treating or preventing a viral disease is disclosed. The method includes administering to an individual in need an effective amount of a food product produced from a plant and a plant part obtained from a seed of a genetically modified plant, and comprises the steps of: (a) generating a recombinant polynucleotide encoding a combination of polypeptides, wherein the polypeptides are sugar-binding proteins, wherein the sugar-binding proteins are encoded by a recombinant polynucleotide encoding the combination of polypeptides, wherein the recombinant polynucleotide encoding the combination of polypeptides is under the control of a promoter selected from heterologous and homologous promoters, wherein the promoter is functional in a plant cell and is operably linked to a coding sequence of the recombinant polynucleotide encoding the combination of polypeptides, which provides ubiquitous expression or plant part-specific target expression from the recombinant polynucleotide; (b) transforming a plant cell with the recombinant polynucleotide of step (a) and regenerating a complete sexually reproduced transformed plant in vitro from the cell, wherein the transformed plant expresses the combination of polypeptides, wherein the polypeptides are sugar-binding proteins. (c) cultivating the transformed plants to obtain seeds of the genetically modified plants, and (d) sowing the seeds of the genetically modified plants to produce genetically modified plants and plant parts for mass production through agricultural practices, horticultural practices and greenhouse cultivation.(e) processing the genetically modified plants and plant parts to obtain food products, wherein the food products exhibit inhibition of viral replication and provide immunity to viral pathogens, wherein the plant parts comprise grains, harvested seeds, and by-products, wherein the mass-produced plants and plant parts are processed to produce food products, wherein the food products comprise bread, cereals, flour, baby food, snack foods, pet food, dried soups, dried beverage mixes, and processed vegetable proteins, wherein the by-products comprise bran, middle rings, mill run, short, red dog, screening, germ flour, germ oil, and producing animal feed and fertilizer, and wherein administration of an effective amount of the food product to an individual in need thereof leads to a reduction or elimination of sites of viral latency in the individual, wherein the sites of viral latency include viral deposits in the intestine and central nervous system (CNS) of the individual.

[0060] In another embodiment of the method of treating or preventing a viral disease disclosed herein, the combination of polypeptides is a combination of glycoproteins in step (a) selected from the group consisting of a combination of two different glycobinding proteins for expression from an exogenous recombinant polynucleotide encoding the combination of polypeptides, selected from the group consisting of three different glycobinding proteins for expression from an exogenous recombinant polynucleotide, four different glycobinding proteins for expression from an exogenous recombinant polynucleotide, five different glycobinding proteins for expression from an exogenous recombinant polynucleotide, and an exogenous recombinant polynucleotide encoding a combination of polypeptides for expression from an exogenous recombinant polynucleotide.

[0061] In another embodiment of the method of treating or preventing a viral disease disclosed herein, the combination of polypeptides is a combination of glyco-binding proteins in step (a) that overcome potential toxicity resulting from the recombinant expression of the glyco-binding proteins in the seeds of the transgenic plant or in plants grown from said seeds and that are combined in a manner that, when expressed as part of the combination of glyco-binding proteins in said combination, reduces the concentration of each glyco-binding protein compared to the recombinant expression of the glyco-binding proteins in said seeds or in plants grown from said seeds. The concentration of each glyco-binding protein in the combination is within the approximate range of 1 milligram / milliliter or 1 mg / ml to 1 attogram / milliliter or 1 ag / ml, and typically within the typical range of 50 microgram / milliliter or 50 μg / ml to 1 picogram / milliliter or 1 pg / ml. Highly active proteins and / or peptide sequences may have activity up to 1-10 ag / mL or 1-10 attogram / mL (attomolar concentrations).

[0062] In another embodiment of the methods of treating or preventing a viral disease disclosed herein, the sugar-binding protein comprises mannose-specific plant lectin, N-acetylglucosamine-specific plant lectin, glucose-specific plant lectin, galactose-specific plant lectin, N-acetylgalactosamine-specific plant lectin, galactose-specific phytoagglutinin, N-acetylgalactosamine-specific phytoagglutinin, glucose-specific phytoagglutinin, and N-acetylglucosamine-specific phytoagglutinin.

[0063] In another embodiment of the method of treating or preventing a viral disease disclosed herein, the carbohydrate-binding protein is a lectin obtained from multiple sources, including glucose / mannose lectin from Lablab bean or Lablab purpureus or Dolichos lablab lectin 1 (DLL-I), GlcNAc-specific agglutinin from tobacco or Nicotiana sp., mannose-specific agglutinin from leek or Allium sp., Galanthus sp.mannose-specific agglutinin from Lotus japonicus rhizome, chitin-specific lectin from Lycoris rhizome, Serpula vermicularis lectin (SVL), mannose-specific agglutinin from Amaryllis or Amaryllis, mannose-specific agglutinin from Galanthus nivalis or Snowdrop, mannose-specific agglutinin from Narcissus pseudonarcissus or Daffodil, mannose-specific agglutinin from Lycoris radiata or Spider lily, mannose-specific agglutinin from Chinese chive, mannose-specific agglutinin from Allium ursinum or Ramson, mannose-specific agglutinin from Colocasia esculenta or Taro, mannose-specific agglutinin from Cymbidium hybrids or Cymbidium orchid, mannose-specific agglutinin from Listera ovata, or Tsey blade, Epipactis Mannose-specific agglutinin from helleborine or broadleaf helleborine, Mannose-specific agglutinin from tulip hybrid or tulip, Mannose-specific agglutinin from Morus Nigra or black viburnum, GlcNAc-specific agglutinin from Phragmites australis or reed, GlcNAc-specific agglutinin from Nicotiana tabacum or tobacco, (GlcNAc)n-specific agglutinin from Urtica dioica or nettle, (GlcNAc)n-specific agglutinin from Hevea brasiliensis or rubber tree, GalNAc-specific agglutinin from Polygonatum multiflorum tetramer or Solomon's seal, GalNAc-specific agglutinin from Bryonia dioica or white bryony, GalNAc-specific agglutinin from Glechoma hederacea or ground ivy, Gal-specific agglutinin from Morus Nigra or black mulberry tree, Gal-specific agglutinin from Artocarpus integrifolia or jackfruit, Sambucus Neu5Acα from elderberry or elderberry (2.6) Gal / GalNAc specific agglutinins, Man / Glc specific agglutinins from Cladastris lutea or Yellowwood, Gal / GalNAc specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Viscum album or Mistletoe, GalNAcα(1,3)Gal > GalNAc > Gal specific agglutinins from Iris hybrids or Iris, Man / GalNAc specific agglutinins from Tulipa hybrids or Tulip, Hippeastrum hybrid agglutinins (HHA), Galanthus nivalis agglutinins (GNA), Cymbidium species agglutinins (CA), Urtica dioica agglutinins (UDA), cytovillin (SVN) isolated from Scytonema varium, sea coral (Gerardia savaglia), griffithsin from Griffithsia sp., or actinohibin from Longisporum albida.

[0064] In another embodiment of the methods of treating or preventing a viral disease disclosed herein, the viral pathogen may be a coronavirus, a rhabdovirus, an influenza virus, a dengue virus, a severe acute respiratory syndrome coronavirus (SARS-CoV), a severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a Middle East respiratory syndrome coronavirus (MERS-CoV), an orthomyxovirus, a hepatitis virus, a hepatitis C virus (HCV), a hepatitis E virus (HEV), an Ebola virus, a polio-measles virus, a retrovirus, an adult T-cell leukemia virus type 1 (HTLV-1), a human immunodeficiency virus (HIV), a norovirus, a cold virus, a West Nile virus, a rabies virus, a polio virus, a mumps virus, a measles virus, a chikungunya virus, a Zika virus, a herpes simplex virus, These include herpes simplex virus, HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1, feline infectious peritonitis virus (FIPV), feline enteric coronavirus (FECV), rinderpest virus, foot-and-mouth disease virus (FMDV), cypovirus (CPV), and reovirus.

[0065] In another embodiment of the method of treating or preventing a viral disease disclosed herein, the transformed plants in step (c) and the genetically modified plants in step (e) include maize, wheat, millet, rye, oats, barley, sorghum, rice, legumes, nuts, and tubers.

[0066] In another embodiment of the methods of treating or preventing a viral disease disclosed herein, an effective amount of food derived from plants and plant parts obtained from seeds of the genetically modified plant is administered with one or more antiviral agents, the antiviral agents including remdesivir, nilmatrixvir (paxlovir) in combination with ritonavir, and molnupiravir.

[0067] In another embodiment of the methods of treating or preventing a viral disease disclosed herein, the individual includes humans, domestic animals, livestock, zoo animals, agricultural livestock, and wild animals.

[0068] In one embodiment of the present invention, this is disclosed as a genetically modified plant seed that inhibits viral growth and confers immunity to viral pathogens, whereby food products obtained from plants and plant parts obtained from said genetically modified plant seed are used, said genetically modified plant seed producing plants and plant parts that confers inhibition of viral growth and immunity to viral pathogens. The plants include corn, wheat, millet, rye, oats, barley, sorghum, rice, legumes, nuts, and tubers, the genetically modified plant seeds are sown to produce plants and plant parts, which are mass-produced by agricultural practices, horticultural practices, and greenhouse cultivation, the plant parts include grains, harvested seeds, and by-products, the mass-produced plants and plant parts are processed to produce food products, which include bread, cereals, flour, baby food, snack foods, pet food, dried soups, dried beverage mixes, and vegetable proteins, the by-products include bran, middle rings, mill run, short, red dog, screenings, germ flour, and germ oil, the by-products produce animal feed and fertilizer, and the food products exhibit inhibition of viral replication and provide immunity against viral pathogens.

[0069] In another embodiment of the genetically modified plant seeds that inhibit viral replication and provide immunity to viral pathogens for use in plants and food products derived from plant parts disclosed herein, the genome of the seed comprises exogenous recombinant polynucleotides encoding a combination of polypeptides, the polypeptides being glyco-binding proteins, and the seed inhibits viral replication and provides immunity to viral pathogens.

[0070] In another embodiment of the genetically modified plant seeds that inhibit viral growth and provide immunity to viral pathogens for use in plants and food products derived from plant parts disclosed herein, the polypeptides in the combination of polypeptides are glycobinding proteins, and the combination of polypeptides is selected from the group consisting of a combination of two different glycobinding proteins for expression from an exogenous recombinant polynucleotide encoding the combination of polypeptides, an exogenous recombinant polynucleotide encoding the combination of polypeptides, a combination of four different glycobinding proteins for expression from an exogenous recombinant polynucleotide encoding the combination of polypeptides, and a combination of five different glycobinding proteins for expression from an exogenous recombinant polynucleotide encoding the combination of polypeptides.

[0071] In another embodiment of the genetically modified plant seeds that inhibit viral growth and provide immunity to viral pathogens for use in plants and food products derived from plant parts disclosed herein, the combination of polypeptides is a combination of sugar-binding proteins encoded by an exogenous recombinant polynucleotide, the exogenous recombinant polynucleotide being under the control of a promoter selected from a heterologous and a homologous promoter, the promoter providing ubiquitous expression or site-specific expression in the plant from the exogenous recombinant polynucleotide encoding the combination of polypeptides, the promoter functioning in a plant cell and being operably linked to an encoding sequence of the recombinant polynucleotide encoding the combination of polypeptides.

[0072] In another embodiment of the genetically modified plant seeds that inhibit viral growth and provide immunity to viral pathogens for use in plants and food products derived from plant parts disclosed herein, the combination of polypeptides is a combination of glyco-binding proteins that are linked in a manner that overcomes potential toxicity resulting from the recombinant expression of the glyco-binding proteins in the genetically modified plant seed or in a plant grown from said seed and reduces the concentration of each glyco-binding protein when expressed as part of the combination of glyco-binding proteins in the combination compared to the recombinant expression of the glyco-binding proteins in the seed or in a plant grown from said seed, and the concentration of each glyco-binding protein in the combination is within the approximate range of 1 milligram / milliliter or 1 mg / ml to 1 attogram / milliliter or 1 ag / ml, and typically within the typical range of 50 microgram / milliliter or 50 μg / ml to 1 picogram / milliliter or 1 pg / ml. Highly active proteins and / or peptide sequences may have activity up to 1-10 ag / mL or 1-10 attogram / mL (attomolar concentrations).

[0073] In another embodiment of the genetically modified plant seeds that inhibit viral growth and provide immunity against viral pathogens for use in foods derived from plants and plant parts disclosed herein, the sugar-binding proteins include mannose-specific plant lectins, N-acetylglucosamine-specific plant lectins, glucose-specific plant lectins, galactose-specific plant lectins, N-acetylgalactosamine-specific plant lectins, galactose-specific phytoagglutinins, N-acetylgalactosamine-specific phytoagglutinins, glucose-specific phytoagglutinins, and N-acetylglucosamine-specific phytoagglutinins.

[0074] In another embodiment of the genetically modified plant seeds that inhibit viral growth and provide immunity against viral pathogens for use in foods derived from plants and plant parts as disclosed herein, the sugar-binding proteins are lectins obtained from multiple sources, including glucose / mannose lectin or Dolichos lablab lectin 1 (DLL-I) from Lablab bean or Lablab purpureus, GlcNAc-specific agglutinin from tobacco or Nicotiana sp., mannose-specific agglutinin from leek or Allium sp., Galanthus sp.mannose-specific agglutinin from Lotus japonicus rhizome, chitin-specific lectin from Lycoris rhizome, Serpula vermicularis lectin (SVL), mannose-specific agglutinin from Amaryllis or Amaryllis, mannose-specific agglutinin from Galanthus nivalis or Snowdrop, mannose-specific agglutinin from Narcissus pseudonarcissus or Daffodil, mannose-specific agglutinin from Lycoris radiata or Spider lily, mannose-specific agglutinin from Chinese chive, mannose-specific agglutinin from Allium ursinum or Ramson, mannose-specific agglutinin from Colocasia esculenta or Taro, mannose-specific agglutinin from Cymbidium hybrids or Cymbidium orchid, mannose-specific agglutinin from Listera ovata, or Tsey blade, Epipactis Mannose-specific agglutinin from helleborine or broadleaf helleborine, Mannose-specific agglutinin from tulip hybrid or tulip, Mannose-specific agglutinin from Morus Nigra or black viburnum, GlcNAc-specific agglutinin from Phragmites australis or reed, GlcNAc-specific agglutinin from Nicotiana tabacum or tobacco, (GlcNAc)n-specific agglutinin from Urtica dioica or nettle, (GlcNAc)n-specific agglutinin from Hevea brasiliensis or rubber tree, GalNAc-specific agglutinin from Polygonatum multiflorum tetramer or Solomon's seal, GalNAc-specific agglutinin from Bryonia dioica or white bryony, GalNAc-specific agglutinin from Glechoma hederacea or ground ivy, Gal-specific agglutinin from Morus Nigra or black mulberry tree, Gal-specific agglutinin from Artocarpus integrifolia or jackfruit, Sambucus Neu5Acα from elderberry or elderberry (2.6) Gal / GalNAc specific agglutinins, Man / Glc specific agglutinins from Cladastris lutea or Yellowwood, Gal / GalNAc specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Viscum album or Mistletoe, GalNAcα(1,3)Gal > GalNAc > Gal specific agglutinins from Iris hybrids or Iris, Man / GalNAc specific agglutinins from Tulipa hybrids or Tulip, Hippeastrum hybrid agglutinins (HHA), Galanthus nivalis agglutinins (GNA), Cymbidium species agglutinins (CA), Urtica dioica agglutinins (UDA), cytovillin (SVN) isolated from Scytonema varium, sea coral (Gerardia savaglia), griffithsin from Griffithsia sp., or actinohibin from Longisporum albida.

[0075] In another embodiment of the genetically modified plant seeds that inhibit viral growth and provide immunity to viral pathogens for use in plants and foods derived from plant parts disclosed herein, the viral pathogen is a coronavirus, a rhabdovirus, an influenza virus, a dengue virus, a severe acute respiratory syndrome coronavirus (SARS-CoV), a severe acute respiratory syndrome coronavirus 1 (SARS-CoV1), a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), a Middle East respiratory syndrome coronavirus (MERS-CoV), an orthomyxovirus, a hepatitis virus, a hepatitis C virus (HCV), a hepatitis E virus (HEV), an Ebola virus, a polio-measles virus, a retrovirus, an adult T-cell leukemia virus type 1 (HTLV-1), a human immunodeficiency virus (HIV), a norovirus, a common cold virus, a West Nile virus, a rabies virus, a polio virus, a mumps virus, a measles virus, a chikungunya virus, a Zika virus, These include herpes simplex virus, HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1, feline infectious peritonitis virus (FIPV), feline enteric coronavirus (FECV), rinderpest virus, foot and mouth disease virus (FMDV), cipovirus (CPV), and reovirus.

[0076] In another embodiment of the genetically modified plant seeds that inhibit viral proliferation and provide immunity to viral pathogens for use in foods obtained from plants and plant parts disclosed herein, the foods are used to treat or prevent viral disease, comprising administering an effective amount of the food to an individual in need thereof, whereby administering an effective amount of the food to an individual in need thereof leads to a reduction or elimination of viral reservoirs in the individual, whereby the viral latency sites include viral deposits in the intestine and central nervous system (CNS) of the individual; an effective amount of the food derived from the plants and plant parts obtained from the genetically modified plant seeds is administered together with one or more antiviral agents, whereby the antiviral agents include remdesivir, nilmatrervir in combination with ritonavir (paxlovid), and molnupiravir, and the individuals include humans, livestock, domestic animals, zoo animals, agricultural livestock, and wild animals.

[0077] The present invention is further illustrated by the following examples, which are intended to be purely illustrative of the invention and should not be construed as limiting the invention in any way.

[0078] Example 1) Preparation of one of the transgenic plants and transgenic plant seeds: The experimental preparation of transgenic plant seeds from a transgenic plant begins with the production of recombinant polynucleotides encoding a combination of sugar-binding proteins such as lectins. Preferably, the combination of lectins is selected in various combinations from Table 2 below, where the recombinant polynucleotides encoding the combinations are under the control of a promoter selected from heterologous and homologous promoters, the promoter providing ubiquitous expression or plant part-specific targeted expression from the recombinant polynucleotides encoding the lectin combinations, the promoter functioning in plant cells and operably linked to the coding sequence of the recombinant polynucleotides encoding the lectin combinations. An example of such an experimental procedure employed is shown diagrammatically in FIG. 1(a). Table 2: Plant-derived lectins with known antiviral activity that were tested in this study (Reference: E. Keyaerts et al. Antiviral Research 75 (2007) 179-187) [Table 2] TIFF2025504584000004.tif68116

[0079] In Table 2 above, monocotyledonous plants (Monocot) refer to the subclass Monocotyledoneae, dicotyledonous plants (Dicot) refer to the subclass Dicotyledoneae, Man refers to mannose, GlcNac refers to N-acetylglucosamine, GalNAc refers to N-acetylgalactosamine, Gal refers to galactose, and Neu5Ac refers to N-acetylneuraminic acid.

[0080] In Table 2 above, Van Damme et al. (1998) refers to Van Damme, E., Peumans, W., Pusztai, A., Bardocz, S., 1998. Handbook of Plant Lectins: Properties and Biomedical Applications. JohnWiley & Sons, Chichester, West Sussex, England.

[0081] In Table 2 above, Van Damme et al. (2002) refers to Van Damme, EJ, Hause, B., Hu, J., Barre, A., Rouge, P., Proost, P., Peumans, WJ, 2002. Two jacalin-related lectins with different specificities and subcellular localizations are major storage proteins in the bark of chromyl (Plant Physiol. 130, 757-769)·.

[0082] In Table 2 above, Chen et al. (2002) refers to Chen, Y., Peumans, WJ, Hause, B., Bras, J., Kumar, M., Proost, P., Barre, A., Rouge, P., Van Damme, EJ, 2002. Jasmonate methyl ester induces the synthesis of cytoplasmic / nuclear chitooligosaccharide-binding lectin in tobacco leaves.

[0083] In Table 2 above, Wang et al. (2003) refers to Wang,W., Peumans,WJ, Rouge, P., Rossi, C., Proost, P., Chen, J.,Van Damme, EJ, 2003. The leaves of Hedera hederacea (ground ivy), a plant of the Lamiaceae family, contain a lectin that is structurally and evolutionarily related to legume lectins. Plant J. 33, 293-304.

[0084] The recombinant polynucleotides encoding the lectin combinations as described above are then introduced into crop plants such as corn or wheat to produce transgenic crops that provide animals or humans consuming the crop with partial or complete protection from exposure to and / or help treat the effects of viral pathogens. Briefly, to produce such transgenic crop varieties, known and routinely used methods well known to those skilled in the art are used, in which the above-prepared recombinant polynucleotides encoding the lectin combinations are inserted into cells of the crop plant (e.g., corn or wheat plants) at the embryonic stage. The resulting mature plants are tested for the presence of the lectin combination in all of their cells, and the expression of said lectins is tested in leaves of the transformed plants. One such mechanism known to those skilled in the art is represented diagrammatically in FIG. 1(b). In test assays, the lectin combination inhibits viral transcription, as is well-established in the literature. Various mechanisms known or suggested in the art that underlie the antiviral activity of lectins are shown diagrammatically in FIG. 2. The resulting seeds of genetically modified maize and wheat plants will have antiviral properties against viral pathogens such as SARS-CoV-2, the causative virus of COVID-19, due to the specific proteins transferred. In this experiment, tests will be carried out to obtain the desired genetically modified plants and genetically modified plant seeds from the genetically modified crops thus obtained.

[0085] Example 2) Microneutralization and plaque reduction assays: In this example, the 50% infectious dose (TCID50) of the virus in MDCK or Vero E6 cells and immune plaque assay (PFU / ml) are determined. The protocol for serological diagnosis of influenza by MN assay uses selected lectin combinations, which are the experimental lectin combinations used in the production of transgenic plants and transgenic plant seeds in Example 1, and individual lectins of the combination for comparison, and a control protein is used instead of serum (World Health Organization, 2011). The experimental lectins, the comparative lectins, the control protein, and the virus are placed in a 96-well tissue culture plate and incubated at 37°C for 1 hour, after which cells are added at 1.5x104 cells / well. They are then cultured in serum-free medium for 18-20 hours, washed, and fixed with 50% methanol 50% acetone. The virus titer is then measured using an anti-NP (influenza virus) or anti-N (coronavirus) ELISA. Plates were blocked with 5% skim milk, 0.5% BSA, and rabbit polyclonal anti-NP or mouse polyclonal anti-N primary antibodies and HRP-conjugated secondary antibodies were added sequentially. Peroxidase substrate solution (TMB) and 1M H2SO4 were used as stop solutions, and absorbance (OD 450 nm) was read on a microplate reader (Victor3. Perkin Elmer, Waltham, Massachusetts).

[0086] Next, for the plaque reduction assay, MDCK or Vero E6 cells are plated in 6-well plates at 2x105 cells / well overnight until 90% confluent. The experimental combinations of lectins, individual lectins in the comparative combinations, and control proteins are co-incubated with the virus for 1 h at 37°C, after which the mixtures are added to the monolayer and incubated for an additional hour. The virus / lectin combination, virus / comparative lectin, and virus / control protein mixtures are aspirated, the cells are washed with PBS, and then the cells are overlaid with 0.5% low-melting agarose in serum-free medium. The plates are allowed to solidify at room temperature for 30 min and then incubated at 37°C for 4–5 days or until cytopathic effect (CPE) is observed. The cells are then fixed with 7.4% formalin, 1% Tween 20, and the agarose plugs are removed. For influenza viruses, immunoplaque assays are performed using rabbit polyclonal antinucleoprotein (NP) primary antibodies and HRP-conjugated secondary antibodies, and plaques are visualized by overnight incubation with KPL TruBlue peroxidase substrate (Seracare, Milford, Massachusetts). For coronaviruses, plates are stained with 0.5% crystal violet.

[0087] Example 3) Toxicity and cell viability assays: In this example, Vero E6 cells are used to evaluate in vitro toxicity and cell viability assays, as shown in Figure 3, and the cells are exposed to the desired experimental concentrations. As shown in Figure 3(a), experimental combinations of lectins of the present disclosure are compared to the individual lectins that form the combination, as shown in Figure 3(b), a control protein that is not known to have a protective effect against viral pathogens, as shown in Figure 3(c), and untreated Vero E6 cells for experimental assays and determinations in Figure 3(d), where the combinations of proteins or individual proteins can be sourced directly from the original plant source and combined at the desired concentrations to match the same concentrations extracted from the experimentally produced transgenic plants and transgenic plant seeds of Example 1 disclosed herein. This example is used to determine and demonstrate the high tolerance and lack of toxicity of the individual and combination of lectins. In particular, it is suggested that the combination is as tolerant as the individual lectins that are part of the experimentally formed lectin combination. This experiment also served to screen for potentially toxic lectin candidates, as shown in Table 2 and Example 1, which were eliminated from further experiments.

[0088] Example 4) In vitro antiviral activity of lectin experimental combinations against SARS-CoV-2 infection: In this example, Vero E6 cells are evaluated in an in vitro assay to determine antiviral activity, as shown in Figure 4, where the cells are exposed to the desired experimental concentrations. As shown in FIG. 4(a), experimental combinations of lectins, as shown in FIG. 4(b), and individual lectins forming said combinations, as shown in FIG. 4(c), and control proteins not known to have a protective effect against viral pathogens, as compared to individual lectins forming said combinations, as shown in FIG. 4(c), and control proteins not known to provide protection against viral pathogens, as compared to individual lectins forming said combinations, as compared to untreated Vero E6 cells, as shown in FIG. 4(d), to experimentally assay and determine protection from viral pathogens such as influenza virus, SARS-CoV-2, feline infectious peritonitis infection in Vero E6 cells, as compared to untreated Vero E6 cells, the protein combinations or individual proteins can be sourced directly from the original plant source and combined at the desired concentrations to match the concentrations extracted from the experimentally generated transgenic plants and transgenic plant seeds of Example 1 disclosed herein. The present examples are used to determine and demonstrate the antiviral activity of the lectin combinations, which are more effective at lower concentrations with higher antiviral activity and lower toxicity, as compared to the individual lectins forming part of the experimental lectin combinations, demonstrating the technical advances and advantageous results of the present disclosure. The experiments also serve as a screen for lectin candidates or lectins that exhibit reduced antiviral activity or inhibitory effects in combination or alone when testing candidate lectins, as shown in Table 2 and Example 1, and are then eliminated from further experiments.

[0089] Example 5) In Vivo Toxicity Assay: This example provides a schematic of an in vivo toxicity and resistance assay in a mouse model exposed to experimental concentrations of the disclosed lectin combinations, compared to the individual lectins that make up the combination, compared to control proteins that are not known to have a protective effect against viral pathogens. Also, experimental assays and determinations are performed in untreated mice to determine toxicity and resistance due to such exposure and treatment, where the protein combinations or individual proteins can be sourced directly from the original plant source and combined at desired concentrations to match the concentrations extracted from the experimentally produced transgenic plants and transgenic plant seeds of Example 1 disclosed herein. Priority is given to candidates selected from the combined results of Examples 3 and 4.

[0090] Example 6) In vivo antiviral activity of experimental combinations of lectins against SARS-CoV-2 infection shown in direct or contact infection models:In vivo antiviral activity of experimental combinations of lectins against SARS-CoV-2 infection shown in direct or contact infection models. In this example, as shown in Figure 5, the in vivo antiviral activity of mice fed a diet consisting of the experimental combination of lectins disclosed herein (a) and (e) at the desired experimental concentrations is compared to the individual lectins forming the combination (b) and (f), and control proteins not known to have a protective effect against viral pathogens (c) and (g), and (d) and (h) untreated mice are experimentally assayed to determine the antiviral activity of such treatment, to determine protection from viral pathogens and infections by pathogens such as influenza virus, SARS-CoV-2, feline infectious peritonitis infection, and (II) contact infection transmission from already infected mice to uninfected mice, where the protein combination or individual proteins can be obtained directly from the original plant source and combined at the desired concentrations to match the concentrations extracted from the experimentally produced transgenic plants and transgenic plant seeds of Example 1 disclosed herein. Priority is given to candidates selected from the combined results of Examples 3 and 4.

[0091] It will be apparent to those skilled in the art that various modifications and variations are possible in the practice of this invention without departing from the scope or spirit of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention. It is intended that the specification and examples be considered as exemplary only, with the true scope and spirit of the invention being indicated by the following claims.

Claims

1. A genetically modified plant seed, comprising: the genome of the seed comprises exogenous recombinant polynucleotides encoding a combination of polypeptides; the polypeptide is a glycobinding protein; The seed inhibits viral replication. Transgenic plant seeds that provide immunity against viral pathogens.

2. wherein the polypeptide in the combination of polypeptides is a glyco-binding protein; The combination of polypeptides is a combination of two different glycobinding proteins for expression from said exogenous recombinant polynucleotide encoding said combination of polypeptides; a combination of three different glycobinding proteins for expression from said exogenous recombinant polynucleotides encoding said combination of polypeptides; a combination of four different glycobinding proteins for expression from said exogenous recombinant polynucleotides encoding said combination of polypeptides; a combination of five different glycobinding proteins for expression from said exogenous recombinant polynucleotide encoding said combination of polypeptides; A genetically modified plant seed according to claim 1.

3. The combination of polypeptides is a combination of glycobinding proteins encoded by said exogenous recombinant polynucleotides encoding said combination of polypeptides; said exogenous recombinant polynucleotide encoding said combination of polypeptides is under the control of a promoter selected from a heterologous and a homologous promoter; said promoters effecting broad-range or plant part-specific targeted expression from said exogenous recombinant polynucleotides encoding said combination of polypeptides; the promoter functions in a plant cell and is operably linked to an encoding sequence of the recombinant polynucleotide encoding the combination of polypeptides; A genetically modified plant seed according to claim 1.

4. the combination of polypeptides is a combination of carbohydrate-binding proteins; the glyco-binding proteins are linked in a manner that addresses potential toxicity from recombinant expression of the glyco-binding proteins in a seed of a genetically modified plant or a plant grown from said seed, and reduces the concentration of each glyco-binding protein when expressed as part of a combination of glyco-binding proteins compared to recombinant expression of the glyco-binding proteins in said seed or a plant grown from said seed; the concentration of each of the glycobinding proteins in the combination is within the approximate range of 1 milligram / milliliter (1 mg / ml) to 1 attogram / milliliter (1 ag / ml), and usually within the typical range of 50 microgram / milliliter (50 μg / ml) to 1 picogram / milliliter (1 pg / ml); Highly potent proteins and / or peptide sequences may have activity up to 1-10 ag / mL or 1-10 attogram / mL (attomolar concentrations). A genetically modified plant seed according to claim 1.

5. The sugar-binding protein includes mannose-specific plant lectin, N-acetylglucosamine-specific plant lectin, glucose-specific plant lectin, galactose-specific plant lectin, N-acetylgalactosamine-specific plant lectin, galactose-specific plant agglutinin, N-acetylgalactosamine-specific plant agglutinin, glucose-specific plant agglutinin, or N-acetylglucosamine-specific plant agglutinin. A genetically modified plant seed according to claim 1.

6. the carbohydrate-binding protein is a lectin obtained from multiple sources; Glucose / mannose lectin or Dolichos lablab lectin 1 (DLL-I) from Lablab bean or Lablab purpureus, GlcNAc-specific agglutinin from tobacco or Nicotiana sp., mannose-specific agglutinin from leek or Allium sp., Galanthus sp.mannose-specific agglutinin from Lotus japonicus rhizome, chitin-specific lectin from Lycoris rhizome, Serpula vermicularis lectin (SVL), mannose-specific agglutinin from Amaryllis or Amaryllis, mannose-specific agglutinin from Galanthus nivalis or Snowdrop, mannose-specific agglutinin from Narcissus pseudonarcissus or Daffodil, mannose-specific agglutinin from Lycoris radiata or Spider lily, mannose-specific agglutinin from Chinese chive, mannose-specific agglutinin from Allium ursinum or Ramson, mannose-specific agglutinin from Colocasia esculenta or Taro, mannose-specific agglutinin from Cymbidium hybrids or Cymbidium orchid, mannose-specific agglutinin from Listera ovata, or Tsey blade, Epipactis Mannose-specific agglutinin from helleborine or broadleaf helleborine, Mannose-specific agglutinin from tulip hybrid or tulip, Mannose-specific agglutinin from Morus Nigra or black viburnum, GlcNAc-specific agglutinin from Phragmites australis or reed, GlcNAc-specific agglutinin from Nicotiana tabacum or tobacco, (GlcNAc)n-specific agglutinin from Urtica dioica or nettle, (GlcNAc)n-specific agglutinin from Hevea brasiliensis or rubber tree, GalNAc-specific agglutinin from Polygonatum multiflorum tetramer or Solomon's seal, GalNAc-specific agglutinin from Bryonia dioica or white bryony, GalNAc-specific agglutinin from Glechoma hederacea or ground ivy, Gal-specific agglutinin from Morus Nigra or black mulberry tree, Gal-specific agglutinin from Artocarpus integrifolia or jackfruit, Sambucus Neu5Acα from elderberry or elderberry (2.6) Gal / GalNAc specific agglutinins, Man / Glc specific agglutinins from Cladastris lutea or Yellowwood, Gal / GalNAc specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Viscum album or Mistletoe, GalNAcα(1,3)Gal > GalNAc > Gal specific agglutinins from Iris hybrids or Iris, Man / GalNAc specific agglutinins from Tulip hybrids or Tulip, Hippeastrum hybrid agglutinins (HHA), Galanthus nivalis agglutinins (GNA), Cymbidium species agglutinins (CA), Urtica dioica agglutinins (UDA), cytovillin (SVN) isolated from Scytonema varium, sea coral (Gerardia savaglia), griffithsin from Griffithsia sp., or actinohibin from Longisporum albida. A genetically modified plant seed according to claim 1.

7. The viral pathogens include coronaviruses, rhabdoviruses, influenza viruses, dengue viruses, severe acute respiratory syndrome coronavirus (SARS-CoV), severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), orthomyxoviruses, hepatitis viruses, hepatitis C virus (HCV), hepatitis E virus (HEV), Ebola virus, polio and measles viruses, retroviruses, adult T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus (HIV), norovirus, cold viruses, West Nile virus, rabies virus, poliovirus, mumps virus, measles virus, chikungunya virus, Zika virus, herpes simplex virus, Herpes simplex virus, HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1, feline infectious peritonitis virus (FIPV), feline enteric coronavirus (FECV), rinderpest virus, foot and mouth disease virus (FMDV), cypovirus (CPV), or reovirus, A genetically modified plant seed according to claim 1.

8. said transgenic plant seeds producing plants and plant parts that suppress viral replication and provide immunity to viral pathogens; The plants include corn, wheat, millet, rye, oats, barley, sorghum, rice, legumes, nuts, or tuberous roots; A genetically modified plant seed according to claim 1.

9. said genetically modified plant seeds being sown to produce plants or plant parts for mass production in agriculture, horticulture or greenhouse cultivation; The plant parts include grains, harvested seeds, and by-products; said commercially produced plants and plant parts are processed to produce food products; The food products include bread, cereals, flour, baby food, snack food, pet food, dry soups, dry drink mixes, and vegetable protein preparations; The by-products include bran, middlings, mill run, shorts, red dogs, screenings, germ, and germ oil; said by-products producing animal feed and fertilizer; The food product inhibits viral replication and provides immunity against viral pathogens. A genetically modified plant seed according to claim 1.

10. A recombinant polynucleotide encoding a combination of polypeptides comprising: the polypeptide is a glycobinding protein; The glycobinding protein is encoded by a recombinant polynucleotide encoding a combination of polypeptides. said recombinant polynucleotides encoding said combination of polypeptides are under the control of a promoter selected from a heterologous and a homologous promoter; said promoters effecting broad-range or plant part-specific targeted expression from said exogenous recombinant polynucleotides encoding said combination of polypeptides; the promoter functions in a plant cell and is operably linked to an encoding sequence of the recombinant polynucleotide encoding the combination of polypeptides; the combination of polypeptides is selected from the group consisting of: a combination of two different sugar binding proteins for expression from the exogenous recombinant polynucleotide encoding the combination of polypeptides; a combination of three different sugar binding proteins for expression from the exogenous recombinant polynucleotide encoding the combination of polypeptides; a combination of four different sugar binding proteins for expression from the exogenous recombinant polynucleotide encoding the combination of polypeptides; and a combination of five different sugar binding proteins for expression from the exogenous recombinant polynucleotide encoding the combination of polypeptides; Sugar-binding proteins include mannose-specific plant lectins, N-acetylglucosamine-specific plant lectins, glucose-specific plant lectins, galactose-specific plant lectins, N-acetylgalactosamine-specific plant lectins, galactose-specific plant agglutinins, N-acetylgalactosamine-specific plant agglutinins, glucose-specific plant agglutinins, or N-acetylglucosamine-specific plant agglutinins. Recombinant polynucleotides.

11. the carbohydrate-binding protein is a lectin obtained from multiple sources; Glucose / mannose lectin or Dolichos lablab lectin 1 (DLL-I) from Lablab bean or Lablab purpureus, GlcNAc-specific agglutinin from tobacco or Nicotiana sp., mannose-specific agglutinin from Welsh onion or Allium sp., Galanthus sp.mannose-specific agglutinin from Lotus japonicus rhizome, chitin-specific lectin from Lycoris rhizome, Serpula vermicularis lectin (SVL), mannose-specific agglutinin from Amaryllis or Amaryllis, mannose-specific agglutinin from Galanthus nivalis or Snowdrop, mannose-specific agglutinin from Narcissus pseudonarcissus or Daffodil, mannose-specific agglutinin from Lycoris radiata or Spider lily, mannose-specific agglutinin from Chinese chive, mannose-specific agglutinin from Allium ursinum or Ramson, mannose-specific agglutinin from Colocasia esculenta or Taro, mannose-specific agglutinin from Cymbidium hybrids or Cymbidium orchid, mannose-specific agglutinin from Listera ovata, or Tsey blade, Epipactis Mannose-specific agglutinin from helleborine or broadleaf helleborine, Mannose-specific agglutinin from tulip hybrid or tulip, Mannose-specific agglutinin from Morus Nigra or black viburnum, GlcNAc-specific agglutinin from Phragmites australis or reed, GlcNAc-specific agglutinin from Nicotiana tabacum or tobacco, (GlcNAc)n-specific agglutinin from Urtica dioica or nettle, (GlcNAc)n-specific agglutinin from Hevea brasiliensis or rubber tree, GalNAc-specific agglutinin from Polygonatum multiflorum tetramer or Solomon's seal, GalNAc-specific agglutinin from Bryonia dioica or white bryony, GalNAc-specific agglutinin from Glechoma hederacea or ground ivy, Gal-specific agglutinin from Morus Nigra or black mulberry tree, Gal-specific agglutinin from Artocarpus integrifolia or jackfruit, Sambucus Neu5Acα from elderberry or elderberry (2.6) Gal / GalNAc specific agglutinins, Man / Glc specific agglutinins from Cladastris lutea or Yellowwood, Gal / GalNAc specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Viscum album or Mistletoe, GalNAcα(1,3)Gal > GalNAc > Gal specific agglutinins from Iris hybrids or Iris, Man / GalNAc specific agglutinins from Tulip hybrids or Tulip, Hippeastrum hybrid agglutinins (HHA), Galanthus nivalis agglutinins (GNA), Cymbidium species agglutinins (CA), Urtica dioica agglutinins (UDA), cytovillin (SVN) isolated from Scytonema varium, sea coral (Gerardia savaglia), griffithsin from Griffithsia sp., or actinohibin from Longisporum albida. The recombinant polynucleotide of claim 10.

12. administering to an individual in need an effective amount of a food product produced from a plant or part of a plant obtained from a seed of the genetically modified plant; (a) producing a recombinant polynucleotide encoding a combination of polypeptides, wherein said polypeptides are sugar-binding proteins, wherein said sugar-binding proteins are encoded by a recombinant polynucleotide encoding a combination of polypeptides, wherein said recombinant polynucleotide encoding the combination of polypeptides is selected from a heterologous and a homologous promoter, said promoter providing ubiquitous expression or plant part-specific targeted expression from said recombinant polynucleotide encoding the combination of polypeptides, said promoter functioning in a plant cell and being operably linked to a coding sequence of said recombinant polynucleotide encoding the combination of polypeptides; (b) transforming a plant cell by introducing the recombinant polynucleotide of step (a) and regenerating a fully fertile transformed plant in vitro from said cell, wherein said transformed plant expresses a combination of polypeptides, wherein said polypeptides are sugar-binding proteins; (c) cultivating said plant to obtain seeds of said genetically modified plant; (d) sowing seeds of the genetically modified plants to produce genetically modified plants and plant parts for mass production by agricultural, horticultural or greenhouse cultivation; (e) processing the genetically modified plants and plant parts to obtain food products, the food products exhibiting an inhibitory effect on viral replication and providing immunity to viral pathogens, the plant parts including grains, harvested seeds, and by-products, and processing the mass-produced plants and plant parts to obtain food products, the food products including bread, cereals, flour, baby food, snack foods, pet food, dried soups, dried beverage mixes, or processed vegetable proteins, the by-products including bran, middle rings, mill run, short, red dog, screening, germ meal, or germ oil, the by-products producing animal feed and fertilizer, and wherein administration of an effective amount of the food product to an individual in need thereof leads to a reduction or elimination of sites of viral latency in the individual, the sites of viral latency including viral deposits in the intestine and central nervous system (CNS) of the individual. A method for treating or preventing a viral disease.

13. the combination of polypeptides is a combination of glyco-binding proteins in step (a), a combination of two different glyco-binding proteins for expression from the exogenous recombinant polynucleotide encoding the combination of polypeptides; a combination of three different glycobinding proteins for expression from said exogenous recombinant polynucleotides encoding said combination of polypeptides; a combination of four different glycobinding proteins for expression from said exogenous recombinant polynucleotides encoding said combination of polypeptides; a combination of five different glycobinding proteins for expression from said exogenous recombinant polynucleotide encoding said combination of polypeptides; The method for treating or preventing a viral disease according to claim 12.

14. the combination of polypeptides is the combination of carbohydrate-binding proteins in step (a); the glyco-binding proteins are linked in a manner that overcomes potential toxicity resulting from the genetically engineered expression of the glyco-binding proteins in a seed of the genetically engineered plant or a plant grown from said seed, and reduces the concentration of each glyco-binding protein when expressed as part of a combination of glyco-binding proteins in said seed or a plant grown from said seed; the concentration of each of the glycobinding proteins in the combination is within the approximate range of 1 milligram / milliliter (1 mg / ml) to 1 attogram / milliliter (1 ag / ml), and usually within the typical range of 50 microgram / milliliter (50 μg / ml) to 1 picogram / milliliter (1 pg / ml); Highly potent proteins and / or peptide sequences may have activity up to 1-10 ag / mL (1-10 attogram / mL) (attomole concentrations). The method for treating or preventing a viral disease according to claim 12.

15. The sugar-binding protein includes mannose-specific plant lectin, N-acetylglucosamine-specific plant lectin, glucose-specific plant lectin, galactose-specific plant lectin, N-acetylgalactosamine-specific plant lectin, galactose-specific plant agglutinin, N-acetylgalactosamine-specific plant agglutinin, glucose-specific plant agglutinin, or N-acetylglucosamine-specific plant agglutinin. The method for treating or preventing a viral disease according to claim 12.

16. the carbohydrate-binding protein is a lectin obtained from multiple sources; Glucose / mannose lectin or Dolichos lablab lectin 1 (DLL-I) from Lablab bean or Lablab purpureus, GlcNAc-specific agglutinin from tobacco or Nicotiana sp., mannose-specific agglutinin from Welsh onion or Allium sp., Galanthus sp.mannose-specific agglutinin from Lotus japonicus rhizome, chitin-specific lectin from Lycoris rhizome, Serpula vermicularis lectin (SVL), mannose-specific agglutinin from Amaryllis or Amaryllis, mannose-specific agglutinin from Galanthus nivalis or Snowdrop, mannose-specific agglutinin from Narcissus pseudonarcissus or Daffodil, mannose-specific agglutinin from Lycoris radiata or Spider lily, mannose-specific agglutinin from Chinese chive, mannose-specific agglutinin from Allium ursinum or Ramson, mannose-specific agglutinin from Colocasia esculenta or Taro, mannose-specific agglutinin from Cymbidium hybrids or Cymbidium orchid, mannose-specific agglutinin from Listera ovata, or Tsey blade, Epipactis Mannose-specific agglutinin from helleborine or broadleaf helleborine, Mannose-specific agglutinin from tulip hybrid or tulip, Mannose-specific agglutinin from Morus Nigra or black viburnum, GlcNAc-specific agglutinin from Phragmites australis or reed, GlcNAc-specific agglutinin from Nicotiana tabacum or tobacco, (GlcNAc)n-specific agglutinin from Urtica dioica or nettle, (GlcNAc)n-specific agglutinin from Hevea brasiliensis or rubber tree, GalNAc-specific agglutinin from Polygonatum multiflorum tetramer or Solomon's seal, GalNAc-specific agglutinin from Bryonia dioica or white bryony, GalNAc-specific agglutinin from Glechoma hederacea or ground ivy, Gal-specific agglutinin from Morus Nigra or black mulberry tree, Gal-specific agglutinin from Artocarpus integrifolia or jackfruit, Sambucus Neu5Acα from elderberry or elderberry (2.6) Gal / GalNAc specific agglutinins, Man / Glc specific agglutinins from Cladastris lutea or Yellowwood, Gal / GalNAc specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Polygonatum multiflorum monomer or Narcissus narcissus, GalNAc (> Gal) specific agglutinins from Viscum album or Mistletoe, GalNAcα(1,3)Gal > GalNAc > Gal specific agglutinins from Iris hybrids or Iris, Man / GalNAc specific agglutinins from Tulip hybrids or Tulip, Hippeastrum hybrid agglutinins (HHA), Galanthus nivalis agglutinins (GNA), Cymbidium species agglutinins (CA), Urtica dioica agglutinins (UDA), cytovillin (SVN) isolated from Scytonema varium, sea coral (Gerardia savaglia), griffithsin from Griffithsia sp., or actinohibin from Longisporum albida. The method for treating or preventing a viral disease according to claim 12.

17. The viral pathogens include coronaviruses, rhabdoviruses, influenza viruses, dengue viruses, severe acute respiratory syndrome coronavirus (SARS-CoV), severe acute respiratory syndrome coronavirus 1 (SARS-CoV1), severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), Middle East respiratory syndrome coronavirus (MERS-CoV), orthomyxoviruses, hepatitis viruses, hepatitis C virus (HCV), hepatitis E virus (HEV), Ebola virus, polio measles virus, retroviruses, adult human T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus (HIV), norovirus, common cold virus, West Nile virus, rabies virus, poliovirus, mumps virus, measles virus, chikungunya virus, Zika virus, Herpes simplex virus, HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1, feline infectious peritonitis virus (FIPV), feline enteric coronavirus (FECV), rinderpest virus, foot and mouth disease virus (FMDV), cipovirus (CPV), or reovirus, The method for treating or preventing a viral disease according to claim 12.

18. The transformed plant of step (c) and the transgenic plant of step (e) include corn, wheat, millet, rye, oat, barley, sorghum, rice, legumes, nuts, or tubers. The method for treating or preventing a viral disease according to claim 12.

19. said effective amount of a food product derived from a plant or plant part obtained from a seed of said genetically modified plant is administered together with one or more antiviral drugs; The antiviral drugs include remdesivir, nilmatrevir (paxlovir) in combination with ritonavir, or molnupiravir. The method for treating or preventing a viral disease according to claim 12.

20. The individual may include a human, a domestic animal, a livestock animal, a zoo animal, a farm animal, or a wild animal. The method for treating or preventing a viral disease according to claim 12.

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