MANNOSE-BINDING LECTIN FOR TREATMENT OR PROPHYLAXIS OF INFECTIOUS DISEASES

Abstract

The present invention is, inter alia, directed towards mannose-binding lectin and compositions comprising mannose-binding lectin for use in treatment or prophylaxis, towards compositions comprising mannose-binding lectin and towards the use of mannose-binding lectin and said compositions. Mannose-binding lectin, or portions thereof are applied locally according to the invention. MBL is binding to a pathogen to prevent it from binding to a host cell by blocking the binding sites of the pathogen. As a result, infection or transmission of disease can be avoided.

Claims

1. A method of performing prophylaxis and/or treatment of an infectious diseases, comprising the step of locally administering mannose-binding lectin (MBL), or portions thereof, to an individual.

2. The method of claim 1, wherein the mannose-binding lectin is administered orally, nasally, or to a mouth, nose, lung, throat, or eye of the individual.

3. The method of claim 1, wherein the mannose-binding lectin is administered by means of a chewing gum, ice cream, a lozenge, a toothpaste, a mouth wash and/or a gargling solution, a nasal spray, nasal drops, a nasal cream, eye drops, an eye cream, or via inhalation or an aerosol spray.

4. The method of claim 1, wherein the mannose-binding lectin is human MBL corresponding to SEQ ID NO:1, particularly recombinant human MBL, or portions thereof, particularly corresponding to SEQ ID NO:2, more particularly corresponding to SEQ ID NO:3.

5. The method of claim 1, wherein the mannose-binding lectin is a plant-derived mannose binding lectin selected from the group consisting of ACA (Allium cepa), APA (Allium porrum), ASA I (Allium sativum), ASA II (Allium sativum), AUA (Allium ursinum), ArtinM (Artocarpus heterophyllus), B7U6V0 (Zingiber officinalis), BanLec (Musa acuminate), ConA (Canavalia ensiformis), DB1 (Dioscorea batatas), LEA (Solanum lycopersicum), Morniga M II (Morus nigra) or Q1 S2H7 (Curcuma zedoria), and GRFT (Griffithsin), or is an animal-derived mannose-binding lectin selected from the group consisting of LvCTL1 (Litopenaeus vannamei), Pl-MBL (Pacifastacus leniusculus), PcLec4 (Pacifastacus clarkia), trout-MBL1 (Oncorhynchus mykiss), trout-MBL2 (Oncorhynchus mykiss) and AbMb (Agaricus bisporus).

6. (canceled)

7. The method of claim 1, wherein the infectious disease is transmitted by the respiratory route.

8. The method of claim 1, wherein the infectious disease is caused by a virus, a bacterium, or a fungus.

9. The method of claim 1, wherein the infectious disease is a Coronaviridae-induced disease, particularly COVID-19.

10. The method of claim 1, wherein the mannose-binding lectin is applied at a concentration of 150 μg/ml or more.

11. The method of claim 1, wherein the mannose-binding lectin is applied every 1 to 24 hours.

12. The method of claim 1, wherein the application of the mannose-binding lectin is started 0 to 60 minutes, particularly 5 to 60 minutes, prior to a presumed exposure to a pathogen and/or wherein the application of the mannose-binding lectin is started 0 to 60 minutes, particularly 5 to 60 minutes, before a gathering with other persons.

13. A composition for use in prophylaxis and/or treatment of infectious diseases, wherein the composition comprises mannose-binding lectin (MBL), or portions thereof, and wherein the composition is adapted for local administration.

14. The composition of claim 13, wherein the composition is a chewing gum, ice cream, a lozenge, a toothpaste, a mouth wash, a gargling solution, a nasal spray, nasal drops, a nasal cream, eye drops, an eye cream or an inhalation preparation.

15. The composition of claim 13, wherein the concentration of mannose-binding lectin is 0.1 to 0.5 wt % of the composition.

16. The composition of claim 13, wherein the mannose-binding lectin has a concentration of 150 μg/ml or more.

17-20. (canceled)

21. The composition of claim 13, wherein the composition is selected from the group consisting of: a chewing gum comprising 25 to 35 wt % of a gum base and 0.1 to 0.5 wt % mannose-binding lectin; an ice cream comprising 0.1 to 0.5 wt % mannose-binding lectin; a toothpaste comprising at least 50 wt % abrasives, 20 to 42 wt % water and 0.1 to 0.5 wt % mannose-binding lectin; a lozenge comprising eucalyptus oil and 0.1 to 0.5 wt % mannose-binding lectin; and a nasal spray comprising water and 0.1 to 0.5 wt % mannose-binding lectin.

22-25. (canceled)

26. The method of claim 1, wherein the mannose-binding lectin is combined with a pharmaceutically acceptable carrier.

27. The method of claim 1, wherein the individual is a human with MBL-deficiency.

28-32. (canceled)

33. The method of claim 1, wherein the mannose-binding lectin is applied to a face mask and the treated face mask is placed over the mouth and nose of the individual.

34. A face mask treated with mannose-binding lectin.

Description

DETAILED DESCRIPTION

[0079] The term “comprising” encompasses “including” as well as “consisting” e.g. a composition “comprising” X may consist exclusively of X or may include something additional e.g. X+Y. In some implementations, the term “comprising” refers to the inclusion of MBL, as well as inclusion of other active agents. However, pharmaceutically acceptable carriers of active agents and other compounds may be included which are for stabilizing, preserving, etc. the composition. These are known by the skilled person in the pharmaceutical industry.

[0080] The local effect of MBL has been described for example in “Mitchell, C. et al. Antiviral Lectins: Selective Inhibitors of Viral Entry. Antiviral Res. 2017 June; 142: 37-54.”

[0081] The respiratory system comprises the nasal cavity, mouth, pharynx, larynx, trachea and lungs.

[0082] Infectious diseases of the respiratory system, but also some other diseases, are transmitted by the respiratory route. This includes airborne transmission by aerosols. The aerosols are predominantly dry and stay in the air for a long time. For example, they are released, when an infective individual is breathing or speaking. An example of an airborne transmitted disease is COVID19. The respiratory route also includes transmission by droplets. These are larger particles that contain water. As they are heavier than aerosols they stay in the air for a shorter time. However, they can remain on surfaces for a longer time and cause transmission of a disease by contact with the contaminated surface. The droplets are usually released, when an infective individual is coughing or sneezing. An example of a disease transmitted by droplets is influenza, but also COVID19.

[0083] Lectins from various sources have been shown to exhibit potent antiviral properties by inhibiting infection of clinically important viral pathogens. Based on prior studies on coronaviruses such as SARS-CoV and MERS-CoV, mannose-specific plant lectins can be used to investigate antiviral properties of the novel coronavirus SARS-CoV-2, the virus that causes COVID-19.

[0084] Some plant-derived and animal-derived mannose-binding lectins have been described in more detail:

[0085] BanLec has been described in detail in “Banana Lectin: A Brief Review, Molecules. 2014 November; 19(11): 18817-18827.”

[0086] Griffithsin is derived from Griffithsia spp. It has been described in “The need for ocular protection for health care workers during SARS-CoV-2 outbreak and a hypothesis for a potential personal protective equipment, Lixiang Wang and Yingping Deng, Front. Public Health, 12 Nov. 2020” and in “Griffithsin with a broad-spectrum antiviral activity by binding glycans in viral glycoprotein exhibits strong synergistic effect in combination with a Pan-Coronavirus fusion inhibitor targeting SARS-CoV-2 spike S2 subunit, Cai et al., Virol Sin., 2020 December; 35(6):857-860”. It also helps for ocular protection.

[0087] B7U6V0 has been described in detail in “https://www.uniprot.org/uniprot/B7U6V0”.

[0088] The mode of action for jackfruit has been described in “Effect of ArtinM on Human Blood Cells During Infection with Paracoccidioides brasiliensis, Luciana Pereira Ruas et al., Front. Microbiol., 4 May 2018”.

[0089] A lectin found in tomato plants, LEA, has been described in “Analysis of Sugar Chain-Binding Specificity of Tomato Lectin Using Lectin Blot: Recognition of High Mannose-Type N-glycans Produced by Plants and Yeast, Suguru Oguri, Glycoconj J 2005 November; 22(7-9):453-61”.

[0090] Garlic lectins bind to high mannose oligosaccharide chains according to “Garlic (Allium sativum) Lectins Bind to High Mannose Oligosaccharide Chains, Tarun Kanti Dam et al., The Journal of Biological Chemistry 273, 5528-5535”.

[0091] A lectin from Curcuma zedoaria Rosc, referred to as Q1S2H7, has be identified as Mannose-binding lectin, and has been described in “Mannose-binding lectin from Curcuma zedoaria Rosc, Tipthara, P, Biol. 50, 167-173 (2007)”.

[0092] Lectins in cyanobacteria and algae have been described in “Mannose-Specific Lectins from Marine Algae: Diverse Structural Scaffolds Associated to Common Virucidal and Anti-Cancer Properties, Annick Barre et al., Mar Drugs. 2019 Aug. 17(8):440.” and “Purification and Characterization of a new Lectin from the Red Marine Alga Hypnea Musciformis, Celso Shiniti Nagano et al., Protein and Peptide Letters 9(2):159-165 April 2002”.

[0093] Another MBL was identified in the Korean mistletoe, and described in “Concanavalin A and Mistletoe Lectin I Differentially Activate Cation Entry and Exocytosis in Human Neutrophils: Lectins May Activate Multiple Subtypes of Cation Channels, K Wenzel-Seifert et al., J Leukoc Biol. 1996 September; 60(3):345-55”.

[0094] MBL found in the rainbow trout has been described in “Molecular cloning and characterisation of two homologues of Mannose-Binding Lectin in rainbow trout, Konstantina Nikolakopoulou et al., Fish & Shellfish Immunology, Volume 21, Issue 3, September 2006, Pages 305-314”.

[0095] Also in shrimp MBL has been describes, for example in “A Novel C-Type Lectin from the Shrimp Litopenaeus vannamei Possesses Anti-White Spot Syndrome Virus Activity, Zhi-Ying Zhao et al., J Virol. 2009 January; 83(1): 347-356”.

[0096] A MBL found in salmon was described in “Identification of a pathogen-binding lectin in salmon serum, K. Vanya Ewart, Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology, Volume 123, Issue 1, May 1999, Pages 9-15”.

[0097] MBL derived from crayfish was described in “An MBL-like protein may interfere with the activation of the proPO-system, an important innate immune reaction in invertebrates, Chenglin Wu, Immunobiology 218(2), February 2012”.

[0098] Also in Bluefin tuna, a MBL has been identified and described in “Isolation and Partial Characterisation of Immunoglobulin From Southern Bluefin Tuna Thunnus maccoyii Castelnau, M Watts et al., Fish Shellfish Immunol 2001 August; 11(6):491-503”.

[0099] Furthermore, in the carp family MBL has been described, e.g. in “The homologue of mannose-binding lectin in the carp family Cyprinidae is expressed at high level in spleen, and the deduced primary structure predicts affinity for galactose, Lars Vitved et al., Immunogenetics 51(11):955-64”.

[0100] Further, MBL has been described in fungi, for example in Agaricus bisporus, e.g. in “Orf239342 from the Mushroom Agaricus bisporus is a Mannose Binding Protein, Heni Rachmawati, Biochem Biophys Res Commun 2019 Jul. 12; 515(1):99-103”.

[0101] As proteins, it is assumed that lectins will not be able to be orally administered as they would not survive digestive enzymes. Antiviral lectins, due to their proteinaceous nature, have not been reported to be biologically-available following oral administration.

[0102] However, some reports suggest, that some lectins withstand the gastrointestinal passage, e.g. garlic lectin (“Dietary garlic (Allium sativum) lectins, ASA I and ASA II, are highly stable and immunogenic, Clement F et al., Int. Immunopharmacol. 2010; 10: 316-32”).

[0103] The stability of the garlic lectins, their ability to withstand the gastrointestinal passage, and their recognition by the immune system prove their effectiveness.

[0104] However, to directly tackle pathogens at the point of entry, the aim is to provide mannose-binding lectin in a way to keep it at the point of entry, e.g. in the mouth or the nose, for some time.

[0105] The administration of Banana Lectin (BanLec) has been discussed in “Molecular Engineering of a Banana Lectin that Inhibits HIV-1 Replication, Michael D. Swanson, University of Michigan”.

[0106] Oral administration of BanLec has been performed in mouse models without deleterious effects. One disadvantage of oral delivery is that it would likely require higher amounts of lectin compared to a vaginally administered form, and it would likely require daily use. Some people have questioned whether consuming bananas could prevent HIV-1 infection. This seems unlikely since a large number of bananas would likely be needed to receive sufficient amounts of BanLec, and that most of the lectin in bananas is bound to starches and may not be effective in that form. Therefore, bananas are not sufficient for oral administration of BanLec.

[0107] The role and expression of MBL in the mucosa was studied in “Role of mannose-binding lectin in intestinal homeostasis and fungal elimination, L Choteau, Mucosal Immunology Vol 9 No 3, May 2016”.

[0108] The translocation of lectins through the mucosa was studied earlier, e.g. in “Identification of intact peanut lectin in peripheral venous blood; Wang Q et al., Lancet. 1998; 352:1831”.

[0109] This has also been studied for the nasal mucosa. Nasal and oral administration have been described, e.g. in “Mucosal immunogenicity of plant lectins in mice, E C Lavelle, Immunology. 2000 January; 99(1): 30-37”.

[0110] The mucosal immunogenicity of plant lectins with different sugar specificities was investigated in mice. For this study Viscum album (mistletoe lectin 1; ML 1), Lycospersicum esculentum (tomato lectin; LEA), Phaseolus vulgaris (PHA), Triticum vulgaris (wheat germ agglutinin (WGA), Ulex europaeus I (UEA 1) were used. Following intranasal or oral administration, the systemic and mucosal antibody responses elicited were compared with those induced by a potent mucosal immunogen (cholera toxin) and a poorly immunogenic protein (ovalbumin; OVA). After three oral or intranasal doses of cholera toxin, high levels of specific serum antibodies were measured and specific IgA was detected in the serum, saliva, vaginal wash, nasal wash and gut wash of mice. Immunization with ovalbumin elicited low titres of serum IgG but specific IgA was not detected in mucosal secretions. Both oral and intranasal delivery of all five plant lectins investigated stimulated the production of specific serum IgG and IgA antibody after three intranasal or oral doses. Immunization with ML 1 induced high titres of serum IgG and IgA in addition to specific IgA in mucosal secretions. The response to orally delivered ML 1 was comparable to that induced by CT, although a 10-fold higher dose was administered. Immunization with LEA also induced high titres of serum IgG, particularly after intranasal delivery. Low specific IgA titres were also detected to LEA in mucosal secretions. Responses to PHA, WGA and UEA 1 were measured at a relatively low level in the serum, and little or no specific mucosal IgA was detected.

[0111] The role of lectin in host defence against microbial infections has been described in “Lectin in host defense against microbial infections, Shieh-Liang Hsieh, 2020”.

[0112] The effectiveness against coronaviruses was investigated, e.g. in “Plant lectins are potent inhibitors of coronaviruses by interfering with two targets in the viral replication cycle, Keyaerts E. et al., Antiviral Res. 2007 September; 75(3):179-87.”

[0113] Coronaviruses and their surface were described e.g. in “Identification of N-linked carbohydrates from severe acute respiratory syndrome (SARS) spike glycoprotein, Ritchie G. et al., Virology. 2010 Apr. 10; 399(2):257-69” or “Post-translational modifications of coronavirus proteins: roles and function, Fung, S. and Liu, D X., Future Virol. (2018) 13(6), 405-430.”

[0114] The use of lectins to increase immune response after oral or nasal administration has also be shown. The following references show that higher concentrations of MBL in mucosa and saliva increase the human immune response. Also, in mice the immune response was improved in some experiments following oral or intranasal administration.

[0115] A higher concentration of MBL in mucosa and salvia was found to increase immune response. This was shown in “Protective role of mouse MBL-C on intestinal mucosa during Shigella flexneri invasion, Da-Ming Zuo et al., Int Immunol. 2009 October; 21(10): 1125-1134.” These findings suggest that mMBL-C may protect host intestinal mucosa by directly binding to the bacteria.

[0116] The expression of MBL not only in the liver, but also in mucosa and the implications of this finding has been discussed in “Mannose-binding lectin and maladies of the bowel and liver, Daniel L Worthley et al., World J Gastroenterol. 2006 Oct. 28; 12(40): 6420-6428.” Although it is clear that the liver is the chief contributor to plasma MBL, mucosal MBL production is relevant in localized immune defence.

[0117] The role of MBL in the immune response in the mouth was investigated e.g. in “Salivary agglutinin is the major component in human saliva that modulates the lectin pathway of the complement system, Sabrina T G Gunput et al., Innate Immunity 2016, Vol. 22(4) 257-265” and “The salivary scavenger and agglutinin binds MBL and regulates the lectin pathway of complement in solution and on surfaces, Martin P. Reichhardt et al., Front. Immunol., 16 Jul. 2012 Vol 3, Art 205”.

[0118] Intranasal application has been studied e.g. in “Mistletoe lectins enhance immune responses to intranasally co-administered herpes simplex virus glycoprotein D2, E. C. Lavelle et al., Immunology 2002 107268-274.” It was found that specific IgA responses were also induced, when lectins were applied intranasally. It was demonstrated, that mistletoe lectins I, II and III improve the immune response of the mucosa.

[0119] As described before in “Mucosal immunogenicity of plant lectins in mice, E C Lavelle, Immunology. 2000 January; 99(1): 30-37”, is was found that oral and intranasal application of plant lectins stimulated the production of specific serum IgG and IgA antibody after three intranasal or oral doses. The response was comparable to a potent mucosal immunogenic substance. Low specific IgA titres were also detected, especially to LEA, in mucosal secretions.

[0120] The effectiveness of local application of lectins was also shown in “Adjuvant Effect of Garlic Lectins (Asa I and Asa Ii) on Mucosal Immunity Induction Following Intranasal Immunization with Ovalbumin Antigen, Siddanakoppalu N Pramod1+ and Yeldur P Venkatesh2, 2013 International Conference on Agriculture and Biotechnology IPCBEE vol. 60(2013)”. Garlic lectins, in particular ASA I, exhibited strong systemic responses by both intradermal and intranasal administration.

[0121] Mannose-binding lectin can be applied in a certain dose by administering a dosage unit comprising the mannose-binding lectin in a suitable concentration.

[0122] For example toothpaste has been shown to be an effective route of administration for enzymes and proteins e.g. in “A randomised clinical study to determine the effect of a toothpaste containing enzymes and proteins on plaque oral microbiome ecology, S. E. Adams et al., Sci Rep. 2017; 7:43344. Published 2017 Feb. 27”; a randomised clinical study to determine the effect of a toothpaste containing enzymes and proteins on plaque oral microbiome ecology. The results demonstrated that a toothpaste containing enzymes and proteins can augment natural salivary defenses to promote an overall community shift resulting in an increase in bacteria associated with gum health and a concomitant decrease in those associated with periodontal disease.

[0123] The present invention is illustrated by the following figures and examples, which do not limit the scope of the invention described in the claims.

EXAMPLES

Example 1: Concentration of MBL

[0124] The following table shows suitable doses for application of human MBL:

[0125] The following doses are safe, and can increase the concentration of human MBL with 1 μg/ml (table 1) or 2 μg/ml (table 2):

TABLE-US-00004 TABLE 1 Human weight kg 100 90 80 70 60 50 40 30 20 Administer μg 571 514 457 400 343 286 229 171 114 twice a day

TABLE-US-00005 TABLE 2 Human weight kg 100 90 80 70 60 50 40 30 20 Administer μg 1 143 1 029 914 800 686 571 457 343 229 twice a day

Example 2: Chewing Gum

[0126] A chewing gum is prepared, wherein the basic ingredients are gum base, softener/plasticizer and MBL.

[0127] Other optional additives can be sweeteners, flavourings and colours. The person skilled in the art knows suitable compositions, e.g. from “Modern chewing gum, Mestres J, (2008) in Fritz, D (ed.). Formulation and Production of Chewing and Bubble Gum (2 ed.). Kennedy's Publications Ltd. pp. 47-73”.

[0128] Chewing gum can come in a variety of formats ranging from 1.4 to 6.9 g per piece, and products can be differentiated by the consumer's intent to form bubbles or the preference for sugar containing or sugarless products.

[0129] The ingredients for the chewing gum in this example are shown in table 3:

TABLE-US-00006 TABLE 3 wt % of the ingredients composition example and/or functionality gum base  25-35% Three main components make up common gum bases: resin, wax, and elastomer. Resin, e.g. terpene, is the main chewable portion. Wax softens the gum. Elastomers add flexibility. sucrose  40-50% Other sweeteners can be used, e.g. other carbohydrates, such as dextrose, glucose or corn syrup. Alternative sweeteners such as erythritol, isomalt, xylitol, maltitol, mannitol, sorbitol, lactitol can also be used. Amounts have to be adapted in line with potency. glycerol  2-15% Moisturizer softener/    1-2% To soften gum by increasing flexibility and reducing plasticizer brittleness by altering the glass transition temperature. Quantities of this additives are altered in order to balance processability and packaging speed. Examples are lecithin, hydrogenated vegetable oils, glycerol ester, lanolin, methyl ester, pentaerythritol ester, rice bran wax, stearic acid, sodium and potassium stearates. flavours 1.5-3.0% Peppermint and spearmint are the most popular flavours. Food acids are implemented to provide a sour flavour (i.e. citric, tartaric, malic, lactic, adipic, and fumaric acids). colours Variable Natural or synthetic colours, appearance coating/ Variable E.g. polyols, such as sorbitol, maltitol I/isomalt, mannitol; humectant Polyols can also be implemented as humectants in form of water absorbent powder dusting in order to maintain the quality and extend the shelf life of the product. mannose- 0.1-0.5% In this example BanLec was used; binding The use of other mannose-binding lectins, e.g. human MBL, lectin is possible.

[0130] Recipe to prepare 100 g of MBL enriched chewing gum.

[0131] Ingredients: [0132] 30 g gum base [0133] 30 g corn syrup [0134] 37 g powdered corn starch [0135] 2 g flavours [0136] 800 mg colour [0137] 200 mg BanLec

[0138] Production

[0139] 30 g gum base are poured into a double stage pot and warmed up with indirect steaming to approximately 100° C. Special care is needed not to introduce any water in the mixture. The mixture is stirred until it is warm and gooey. Instead of indirect steaming, one can use microwavable pot and warm up for approximately 30 sec at 115° C. until it is warm and gooey.

[0140] 30 g corn syrup are poured into a clean double stage indirect steaming pot and warmed up to make it a smooth liquid, alternatively corn syrup is warmed up for 25 sec inside a microwave at 120° C.

[0141] The gooey gum base and liquified corn syrup are mixed and 2 g flavours, 800 mg of a desired colour are added, Mixing is continued for 5 minutes to form a uniform smooth mixture.

[0142] 27 g of corn starch powder are added to the mixture and mixing is continued for 10 minutes. Subsequently, the mixture is mixed and cooled down in a two-stage pot with water cooling outside until reaching to 35° C. Parallel to the previous step, 10 g powder corn starch are mixed with 200 mg BanLec to a homogenic powder mixture.

[0143] Once the mixtures of gum base and corn starch is cooled down to 35° C., the powder mixture of corn starch and BanLec is added. Kneading is continued for 10 minutes to form the chewing gum composition.

[0144] The composition can be formed and cut to small pieces 70 pieces of 1.43 g per piece are provided. e Each piece contains 2.86 mg (2860 μg) of BanLec.

[0145] The mass balance equations below show that using one piece of chewing gum weighing 1.43 g that contains 2.86 mg BanLec for 15 minutes, can activate mouth media with a sufficient amount of free BanLec to protect the host exposed to a highly virus contaminated environment.

[0146] A first amount of MBL(BanLec) binds to virus particles. A second amount of MBL(BanLec) is bound to the mannose or oligosaccharides inside the chewing gum. A third amount of MBL(BanLec) is bound to polysaccharides such as starches that are released during chewing by the effect of amylase enzyme in salvia. A fourth amount of 4-MBL(BanLec) is swallowed. A fifth amount of MBL(BanLec) remains in the mouth media due to surface layer generated. A sixth amount of MBL(BanLec) is unbound or free MBL in mouth media.

[0147] For an effective inhibition the following equations apply:

[00001]${\stackrel{.}{m}}_t={\stackrel{.}{m}}_1+{\stackrel{.}{m}}_2+.Math.{\stackrel{.}{m}}_6=\underset{i=1}{\overset{6}{.Math.}}{\stackrel{.}{m}}_i$

[0148] {dot over (m)}.sub.1 is a function of time and virus contamination in the media that a host is exposed to.

{dot over (m)}.sub.1=f(N.sub.viruses,δt)

[0149] {dot over (m)}.sub.2 is a function of oligosaccharides and mannose contents in chewing gum.

{dot over (m)}.sub.2=f(M.sub.sugar)

[0150] {dot over (m)}.sub.3 is a function of time and effects of amylase enzyme on polysaccharides like starch.

{dot over (m)}.sub.3=f(M.sub.starch,δt)

[0151] {dot over (m)}.sub.4 is a function of time and swallow up.

{dot over (m)}.sub.4=f({dot over (Q)}.sub.swallow-up,δt)

({dot over (m)}.sub.5+{dot over (m)}.sub.6)≥{dot over (m)}.sub.1

[0152] Based on the current example

[00002]${\stackrel{.}{m}}_1=f\left(N_{\mathrm{viruses}}\left(16000\right),\delta t\left(3\mathrm{hr}\right)\right){\stackrel{.}{m}}_2=f\left(M_{\mathrm{sugar}}\left(\frac{30\mathrm{gr}}{70\mathrm{piece}}\right)\right){\stackrel{.}{m}}_3=f\left(M_{\mathrm{starch}}\left(\frac{37\mathrm{gr}}{70\mathrm{piece}}\right),\delta t\left(3\mathrm{hr}\right)\right)$

[0153] Humans swallow between 500-700 times a day, around 3 times an hour during sleep, once per minute while awake and even more during meals.

{dot over (m)}.sub.4,min=f({dot over (Q)}.sub.swallow-up,min(3×3×100 ml),δt(3 hr))

{dot over (m)}.sub.4,max=f({dot over (Q)}.sub.swallow-up,max(1×3×60×100 ml),δt(3 hr))

Example 3: Throat Lozenges

[0154] Throat lozenges are prepared according to the following procedure: As basic ingredients, carbohydrate sweeteners can be used. Alternative sweeteners, such as isomalt may also be used. Additionally, either zinc gluconate glycine, zinc acetate or pectin can be added as an oral demulcent. Mannose-binding lectin is added to this basis.

[0155] The person skilled in the art is familiar with many other ingredients that can be added to throat lozenges such as: tart green apple extract, glycerol, manuka honey, aloe vera, American ginseng, lysozyme, and orchid extract. Lozenges may also contain benzocaine, an anaesthetic, or eucalyptus oil. Optional additives such as dextromethorphan can be used as well.

[0156] The moisture content and weight of hard candy lozenge should be between, 0.5 to 1.5% and 1.5 to 4.5 g respectively. Depending on the weight per piece, the content of mannose-binding lectin varies. In this example it was 0.1 to 0.5 wt % of the composition. However, more or less than that are also possible.

[0157] Table 4 lists ingredients for throat lozenges:

TABLE-US-00007 TABLE 4 wt % of the ingredients composition example and or functionality benzocaine 7.75% Is an ester local anaesthetic commonly (optional) (up to 20%) used as a topical pain reliever or in cough drops. menthol (optional) Eucalyptus oil 3.1 mg Eucalyptus oil is the generic name for distilled oil from the leaf of eucalyptus, a genus of the plant family myrtaceae native to Australia and cultivated worldwide. zinc gluconate Zinc gluconate is the zinc salt of gluconic glycine acid. It is an ionic compound consisting of two anions of gluconate for each zinc(II) cation. Zinc gluconate is a popular form for the delivery of zinc as a dietary supplement. Zinc gluconate has been used in lozenges for treating the common cold. Alternatively, zinc acetate can be used that has been found to have a greater effect on the duration of colds. pectin Demulcent; A demulcent is an agent that forms a soothing film over a mucous membrane, relieving minor pain and inflammation of the membrane. Demulcents are sometimes referred to as mucoprotective agents. Demulcents such as pectin, glycerine, honey, and syrup are common ingredients in cough mixtures and cough drops. Methylcellulose, propylene glycol, and glycerine are synthetic demulcents. dextromethorphan sweeteners e.g. natural honey (additional effect as demulcent) flavours Lemon, orange, etc Mannose-binding 0.1-0.5% BanLec or another mannose-binding lectin lectin, e.g. human MBL

[0158] For production of the throat lozenges mannose-binding lectin solution is mixed with the base ingredients, when the temperature of the base mixture is 38-40° C. Mannose-binding lectin solution is added and mixing continues for 10 minutes. A throat lozenge can be applied twice a day to support the immune system.

[0159] Recipe to Prepare Throat Lozenges

[0160] Ingredients [0161] 1 cup of sugar [0162] ½ cup of water [0163] 1 tablespoon of lemon juice [0164] 1 tablespoon of honey [0165] ½ teaspoon of ground ginger [0166] ¼ teaspoon of ground cloves [0167] 10 g powder corn starch [0168] 200 mg BanLec

[0169] Production

[0170] Sugar and water are added into a pot, a tablespoon of lemon juice is added into the pot. The lemon juice will provide some vitamin C. Honey, ginger and ground cloves are added into the mixture.

[0171] The honey is antibacterial, soothes the throat, and is a cough suppressant. The ginger helps maintain the immune system, is an anti-inflammatory, helps with pain relief, and also alleviates of nausea. Ground cloves reduce phlegm, and are also a source of antioxidants. The ingredients are heated and stirred together. Once simmering the mixture is stirred regularly for 15 to 20 minutes. Subsequently, the mixture is left to cool until the liquid is thick and syrupy. Little dots are poured on parchment paper to form the lozenges.

[0172] Parallel to the previous step, sugar, 10 g powder corn starch and 200 mg BanLec are mixed to form a completely homogenic powder mixture. The lozenges are evenly covered with the powdered mixture.

Example 4: Toothpaste

[0173] For this example, a toothpaste as generally known by a person skilled in the art was used. Additives can be added, such as: fluoride, glycerol, sorbitol, calcium carbonate, sodium lauryl sulphate. Additionally, mannose-binding lectin is added in this example.

[0174] The content of mannose-binding lectin varies, from 0.1 to 0.5 wt %. More or less than that can be added in another embodiment.

[0175] Table 5 lists ingredients for the toothpaste.

TABLE-US-00008 TABLE 5 wt % of the ingredient composition example and or functionality abrasives at least 50% These insoluble particles help remove plaque from the teeth. The removal of plaque and calculus prevents the accumulation of tartar and is widely claimed to help minimize cavities and periodontal disease. Representative abrasives include particles of aluminum hydroxide (Al(OH)3), calcium carbonate (CaCO3), various calcium hydrogen phosphates, various silicas and zeolites, and hydroxyapatite (Ca5(PO4)3OH). fluoride 1000-1450 ppm Fluoride in various forms is the most popular active or ingredient in toothpaste to prevent cavities. The 0.312% w/w additional fluoride in toothpaste has beneficial effects on the formation of dental enamel and bones. Sodium fluoride (NaF) is the most common source of fluoride, but stannous fluoride (SnF2), olaflur (an organic salt of fluoride), and sodium monofluorophosphate (Na2PO3F) are also used. Stannous fluoride has been shown to be more effective than sodium fluoride in reducing the incidence of dental caries and controlling gingivitis but causes somewhat more surface stains. surfactants Many, although not all, toothpastes contain sodium or lauryl sulfate (SLS) or related surfactants detergents (detergents). SLS is found in many other personal care products as well, such as shampoo, and is mainly a foaming agent, which enables uniform distribution of toothpaste, improving its cleansing power. water 20-42% antibacterial Triclosan, an antibacterial agent, is a common agents toothpaste ingredient in the United Kingdom. Triclosan or zinc chloride prevent gingivitis and, according to the American Dental Association, helps reduce tartar and bad breath. flavour The three most common flavourings are peppermint, spearmint, and wintergreen. Toothpaste flavoured with peppermint-anise oil is popular in the Mediterranean region. These flavours are provided by the respective oils, e.g. peppermint oil. More exotic flavours include anethole anise, apricot, bubblegum, cinnamon, fennel, lavender, neem, ginger, vanilla, lemon, orange, and pine. Alternatively, unflavoured toothpastes can be provided. remineralizers Hydroxyapatite nanocrystals and a variety of calcium phosphates are included in formulations for remineralization, i.e. the reformation of enamel. miscellaneous Agents are added to suppress the tendency of components toothpaste to dry into a powder. Included are various sugar alcohols, such as glycerol, sorbitol, or xylitol, or related derivatives, such as 1,2- propylene glycol and polyethyleneglycol. Strontium chloride or potassium nitrate is included in some toothpastes to reduce tooth sensitivity. mannose- 0.1-0.5% BanLec or another mannose-binding lectin, e.g binding lectin human MBL

[0176] When the temperature of the base mixture is appropriate (lower than 38 or 38-40° C.), MBL powder can be added and mixing continues for 10 minutes.

[0177] At least two times toothbrush per day is recommended. The immune response can be enhanced.

[0178] Recipe to Prepare Toothpaste

[0179] Ingredients [0180] ½ cup coconut oil [0181] 2-3 TBSP baking soda [0182] 2 small packets stevia powder [0183] 15-20 drops peppermint essential oil (or cinnamon essential oil) [0184] 10 drops myrrh essential oil (optional) [0185] 10 g powder corn starch [0186] 200 mg BanLec

[0187] Production

[0188] Coconut oil is melted and baking soda and stevia powder are added. The mixture is cooled while mixing is continued and the essential oil is added. Parallel to the previous step powder corn starch and 200 mg BanLec are mixed to form a homogenic powder mixture. The powder mixture is added to the cooled mixture to provide a toothpaste composition.

Example 5: Mouthwash or Gargling Liquid

[0189] In this example, a mouthwash or gargling liquid is prepared. The basic ingredients are known to the person skilled in the art. A mouthwash or gargling liquid may contain alcohol, benzydamine, benzoic acid, betamethasone, cetylpyridinium chloride (antiseptic, antimalodor), chlorhexidine digluconate and hexetidine (antiseptic), edible oils, essential oils and phenols. The present composition additionally comprises a mannose-binding lectin.

[0190] The content of mannose-binding lectin varies, in this example from 0.1 to 0.5 wt %. In another embodiment more or less than that can be comprised.

[0191] Table 6 lists ingredients for mouthwash/gargling solution

TABLE-US-00009 wt % of the Ingredient composition example and or functionality alcohol Alcohol is added to mouthwash not only to destroy pathogens, e.g. bacteria, but to act as a carrier agent for essential active ingredients such as menthol, eucalyptol and thymol, which help to penetrate plaque. benzydamine Analgesics; In painful oral conditions such as aphthous stomatitis, analgesic mouth rinses are sometimes used to ease pain, commonly used before meals to reduce discomfort while eating. benzoic acid Acts as a buffer betamethasone Betamethasone is sometimes used as an anti- inflammatory, corticosteroid mouthwash. It may be used for severe inflammatory conditions of the oral mucosa such as the severe forms of aphthous stomatitis. cetylpyridinium  .sup. 0.05% Antiseptic, antimalodor; chloride Cetylpyridinium chloride containing mouthwash is used in some specialized mouthwashes for halitosis. chlorhexidine 0.12-0.2%  Antiseptic; digluconate and Chlorhexidine digluconate is a chemical antiseptic. hexetidine It has anti-plaque action, but also some anti-fungal action. edible oils Phenolic compounds include essential oil essential oils and constituents that have some antibacterial phenols properties, like phenol, thymol, eugenol, or eucalyptol. Essential oils are oils are extracted from plants. Mouthwashes based on essential oils could be more effective than traditional mouthcare-for anti- gingival treatments. They have been found effective in reducing halitosis and are being used in several commercial mouthwashes. fluoride Prevention of cavities flavouring agents and xylitol Hydrogen   .sup.  1.5% Hydrogen peroxide can be used as an oxidizing peroxide mouthwash. It kills anaerobic bacteria, and also has a mechanical cleansing action when it froths as it comes into contact with debris in mouth. lactoperoxidase Saliva substitute; Enzymes and proteins such as lactoperoxidase, lysozyme, lactoferrin have been used in mouthrinses (e.g. Biotene) to reduce oral bacteria and hence the acid produced by bacteria. Lidocaine Lidocaine is useful for the treatment of mucositis symptoms (inflammation of mucous membranes) that is induced by radiation or chemotherapy. methyl salicylate Methyl salicylate functions as an anti-septic, anti- inflammatory, analgesic, flavouring, and fragrance. Methyl salicylate has some anti-plaque action, but less than chlorhexidine. Methyl salicylate does not stain teeth. nystatin Nystatin suspension is an antifungal ingredient used for the treatment of oral candidiasis. potassium oxalate A randomized clinical trial found promising results in controlling and reducing dentine hypersensitivity when potassium oxalate mouthrinse was used in conjugation with toothbrushing. sanguinarine Sanguinarine-containing mouthwashes are marketed as anti-plaque and anti-malodor. sodium Sodium bicarbonate is sometimes combined with bicarbonate salt to make a simple homemade mouthwash, indicated for any of the reasons that a salt water mouthwash might be used. Pre-mixed mouthwashes of 1% sodium bicarbonate and 1.5% sodium chloride in aqueous solution are marketed. sodium chloride Salt water mouth wash is made by dissolving 0.5 to 1 teaspoon of table salt into a cup of water, sodium lauryl Foaming agent; sulfate Sodium lauryl sulfate (SLS) is used as a foaming agent in many oral hygiene products including many mouthwashes. Some may suggest that it is probably advisable to use mouthwash at least an hour after brushing with toothpaste when the toothpaste contains SLS, since the anionic compounds in the SLS toothpaste can deactivate cationic agents present in the mouth rinse. sucralfate Sucralfate is a mucosal coating agent, composed of an aluminum salt of sulphated sucrose. tetracycline Antibiotic; Tetracycline is an antibiotic which may sometimes be used as a mouthwash in adults. It is sometimes use for herpetiforme. tranexamic acid 4.8% tranexamic acid solution is sometimes used as an antifibrinolytic mouthwash to prevent bleeding during and after oral surgery in persons with coagulopathies (clotting disorders) or who are taking anticoagulants (blood thinners such as warfarin) triclosan Triclosan is a non-ionic chlorinate bisphenol antiseptic found in some mouthwashes. When used in mouthwash (e.g. 0.03%), there is moderate substantivity, broad spectrum anti-bacterial action, some anti-fungal action and significant anti-plaque effect, especially when combined with copolymer or zinc citrate. Triclosan does not cause staining of the teeth. Zinc chloride Astringents like zinc chloride provide a pleasant- tasting sensation and shrink tissues. Zinc when used in combination with other anti-septic agents can limit the build-up of tartar. Mannose-binding 0.1-0.5% BanLec or another mannose-binding lectin, e.g lectin human MBL

[0192] When the temperature of the base mixture is appropriate (lower than 38 or 38-40° C.), mannose-binding lectin solution is added and mixing continues for 10 minutes.

[0193] Two times gargling per day is recommended. The immune system can be supported to tackle infectious diseases.

[0194] Gargling Solution:

[0195] Ingredients [0196] 100 ml warm water [0197] 2 g of salt [0198] 1 g powder corn starch [0199] 200 mg BanLec

[0200] Production

[0201] Salt is dissolved in warm water. Parallel to the previous step, 1 g powder corn starch is mixed with 200 mg BanLec to form a homogenic powder mixture. The powder mixture is dissolved inside the cooled solution to provide a gargling composition.

Example 6: Nasal and or Oral Drops

[0202] In this example nasal and or oral drop was prepared. Basic ingredients are known to a person skilled in the art. In this example, water, and sodium chloride are used. Additionally, mannose-binding lectin is added. The concentration of mannose-binding lectin varies in this example from 0.1 to 0.5 wt %. In another embodiment more or less than that can be comprised.

[0203] Table 7 lists ingredients for nasal and or oral drops

TABLE-US-00010 wt % of the ingredient composition example and or functionality Water This is the main ingredient sodium hypertonic (3% sodium chloride or sea water), isotonic chloride (0.9% sodium chloride) and hypotonic (0.65% sodium (optional: chloride). e.g. saline Isotonic solutions have the same salt concentration as sprays) the human body, whereas hypertonic solutions have a higher salt content and hypotonic solutions have a lower salt content. plant- eucalyptus, ginger, capsaicin, tea-tree oil derived ingredients (optional) mannose- 0.1-0.5% BanLec or another mannose-binding lectin, e.g. human binding lectin MBL

[0204] When the temperature of the base mixture is appropriate, mannose-binding lectin solution is added, and mixing continues for 10 minutes. The 10 drops of this mixture can be used every 3 hours.

[0205] Recipe to prepare Nasal and Oral drops

[0206] Ingredients [0207] 100 ml purified water [0208] 1 g sea salt [0209] 0.5 g baking soda [0210] 1 g powder corn starch [0211] 200 mg BanLec

[0212] Production

[0213] The water is heated and sea salt and baking soda are added. The mixture is stirred until the solution is completely dissolved. Then the solution is left to cool. Once the solution is created, remove the pot from the stove, and let the solution cool. Parallel to the previous step, 1 g powder corn starch are mixed with 200 mg BanLec to form a homogenic powder mixture. The powder mixture is dissolved in the cooled solution to provide a nasal and or oral drops composition.

Example 7: Aerosol Spray

[0214] The oral and/or nasal spray can be used at the point of entry into the body for prophylaxis or treatment of infectious diseases, particularly respiratory diseases, such as COVID-19.

[0215] Inhalation solution and suspension products are aqueous-based formulations that contain active ingredients and can also contain additional excipients. Aqueous-based oral inhalation solutions and suspensions must be sterile. Inhalation solutions and suspensions are intended for delivery to the lungs by inhalation for local and/or systemic effects and are to be used with a nebulizer.

[0216] The products contain active ingredients and can also contain additional excipients (viscosity modifiers, emulsifiers, buffering agents). MBL(BanLec) is one of the main active ingredients in the present formulation

[0217] The use of preservatives or stabilizing agents in inhalation spray formulations is discouraged and is the same here. The solution should be stored in special inhalators.

[0218] The dose is delivered by the integral pump components of the inhaler to the lungs by oral inhalation for local and/or systemic effects. The inhaler comprises a container, closure, and pump.

[0219] Metered dose inhalers for inhalation spray products operate on the basis of mechanical or power assistance and/or energy from the patient's inspiration to produce the aerosol.

[0220] Ingredients [0221] 100 ml water (ad injectionem) [0222] 0.9 g NaCl [0223] buffer [0224] 150 mg BanLec [0225] 0.5 g essence (optional)

[0226] Production

[0227] Water is poured into a sterile container and BanLec and NaCl are added. The solution is mixed and during mixing buffer (e.g. HEPES) is added. The pH-value is adjusted to 7.5. If desired, an essence can be added to the mixture. The mixture is filled into an inhaler that can nebulize the mixture to provide an aerosol spray.

Example 8: Eye Drops

[0228] Ingredients [0229] 100 ml water (ad injectionem) [0230] 0.9 g Na Cl [0231] Buffer [0232] 150 mg BanLec [0233] 0.4 g polyethylene glycol 400 [0234] 0.3 g propylene glycol

[0235] Production

[0236] Water is poured into a sterile container and BanLec, NaCl, polyethylene glycol, and propylene glycol are added. The solution is mixed and buffer (e.g. HEPES) is added during mixing to adjust the pH-value to 7.5.

Example 9: Ice Cream

[0237]

TABLE-US-00011 Cream ice cream % Fruit sorbet vegan % Whole milk 60 Fruit pulp (e.g. strawberry) 50 Cream 32% fat 9.2 Water 21.2 Egg pasteurized 6 Sugar 20 Sugar 15 Glucose syrup 2 Skimmed milk powder 3 Lemon juice 2 Dextrose 2.5 Dextrose 2.5 Inulin 1.5 Inulin 1.5 Glucose syrup 2 Salt 0.1 Salt 0.1 Guar gum 0.2 Guar gum 0.2 Locust bean gum 0.4 Locust bean gum 0.4 MBL (BanLec) 0.1 MBL (BanLec) 0.1 Total 100 Total 100

[0238] Possible Further Ingredients: [0239] Invert sugar [0240] Cane sugar [0241] Baobab [0242] Fructose [0243] Emulsifier E471 [0244] Citric acid [0245] Milk substitute [0246] Maltodextrin [0247] various binders [0248] Flavour defining [0249] ingredients: [0250] Vanilla [0251] Nut pulp [0252] various fruits [0253] Coffee [0254] Cocoa

[0255] Experiments

[0256] For all experiments a stock solution of 2.2 E+06 PFU/mL of Human 2019-nCoV Isolate is used and various viral working stocks are grown in Vero CCL81 cells using fetal calf serum (FCS)-free cell culture medium (OptiPro from Gibco). The working stock aliquots used in the experiment are the virus passage (VP) 2 with a PFU/ml of 1.74 E+04.

[0257] Vero-cells CCL81 (3 E+04 cells/well in serum free Gibco OptiPro) are seeded into 48 well plates 24 hrs. prior to infection. The virus is stored at −80° C. with cells. To purify the virus suspension is centrifuged for 1 min at 13.000 rpm. The cell pellet stays in the vial and the pure virus supernatant is used for the experiment. The virus is pre-incubated with the substance for 1 hr at 37° C. with 5% CO2. With 200 μl of the virus substance mix, there is a final virus load of 2 μl virus on the cells for the infection. The plate is incubated for 60 min at 37° C. with 5% CO2.

[0258] 1-hour post infection the cells are washed two times with PBS and covered with 440 μl fresh pre-warmed cell culture medium (Gibco OptiPro).

[0259] After 10 minutes of incubation at RT 140 μl from the cell culture medium supernatant is removed to determine the starting concentration of viral copy numbers (t=0 h). Constant Ct-values are reached around 27 after the two washing steps. The samples are stored under −80° C. After 48 hrs. of incubation again under previous conditions (37° C. with 5% CO2), further 140 μl of cell culture medium supernatant is obtained (t=48 h) and RNA is isolated immediately to determine virus copy numbers.

[0260] The experiments include internal controls for the efficiency of infection. Cells infected with virus without any substance addition (positive control) and cells not infected with virus (negative control). Both were handled the same as the substance samples in the view of dilution, time, conditions and earning supernatant for further treatment.

[0261] Viral RNA was isolated from cell culture medium supernatant by using QIAamp® Viral RNA Mini Kit, as recommended by CDC.

[0262] The RT-qPCR, to detect the viral load of the samples, was performed based on the CDC recommendation using QuantiTect Multiplex RT-PCR Kit with a Rotor Gene Q cycler:

TABLE-US-00012 2019-nCoV_N1-F 2019-nCoV_N1 Forward Primer 5′-GAC CCC AAA ATC AGC GAA AT-3′ 2019-nCoV_N1-R 2019-nCoV_N1 Reverse Primer 5-TCT GGT TAC TGC CAG TTG AAT CTG-3′ 2019-nCoV_N1-P 2019-nCoV_N1 Probe 5′-FAM-ACC CCG CAT TAC GTT TGG TGG ACC-BHQ1-3′ FAM, BHQ-1

[0263] All Ct-values higher than 40 are considered negative and undetermined. Virus replication was assessed by comparing Ct values after infection (t=0 h) with Ct values after different time-periods of culturing. If there is a difference of minimum 4 cycles (t=48 is higher) we can see an inhibition of the virus replication in the cells.

[0264] Test 1

[0265] A virus neutralization assay is performed following the experimental procedures as described above using human MBL (hMBL) at a concentration of 0.5 mg/ml. Commercially available SARS-CoV-2 is incubated with commercially available human MBL. The hMBL is used in a dilution with a final concentration of 250 μg/ml. Target cells (Vero, primate) are incubated with the mixture of hMBL and SARS-CoV-2. Virus concentration in the cell culture supernatant is determined by SARS-CoV-2 qRT-PCR at 48 hrs after infection. As positive control SARS-CoV-2 without MBL pre-treatment is used and as negative control a sham sample is used. After 48 h the supernatant is removed and analysed for virus-RNA. The hMBL neutralization experiment was performed in three technical replicates. The results are shown in FIG. 1. The qRT-PCR results showed in the triplicates with hMBL viral RNA concentration in the cell culture supernatant a mean of 33.75 cycles (Ct value) with a standard deviation of 0.659. Compared to the positive controls (duplicates), which are infected with the same amount of virus but without hMBL-pre-incubation yielded Ct values of 15.7 and 17.62, respectively. Based on the difference of Ct values between positive controls (mean Ct 16.66) and hMBL-inactivated tests (mean Ct 33.75) a 1,396*105-fold reduction of virus load by hMBL can be calculated. Virus-RNA-levels in the test sample are only marginally higher than in the sham sample, while in the positive control sample RNA-levels are considerably higher. It is shown that recombinant, human MBL is able to inhibit infection of target cells.

[0266] Test 2

[0267] Commercially available SARS-CoV-2 is incubated with 150 μg/ml, 200 μg/ml, and 250 μg/ml of commercially available recombinant BanLec (Banana lectin). Target cells (Vero, primate) are incubated with the mixture of MBL and SARS-CoV-2 for 5 minutes, 15 minutes, 30 minutes and 1 hour. Each experiment is carried out three times. As positive control SARS-CoV-2 without MBL pre-treatment is used and as negative control a sham sample is used. After 1 hour the supernatant is removed and analysed for virus-RNA. The results of the mean value after 5 min and 15 min of 150 μg/ml, 200 μg/ml, and 250 μg/ml is shown in FIG. 2. Virus-RNA-levels in the test sample is only marginally higher than in the sham sample, while in the positive control sample RNA-levels is considerably higher. It is shown that recombinant BanLec is able to inhibit infection of target cells (Vero, primate) even within a very short time frame very efficiently.

[0268] Test 3

[0269] The experimental conditions are as described in test 2. 2 μl virus suspension corresponds to a MOI=0.002 and is used in each well for infection. Virus neutralizing activity of 250 μg/ml BanLec with 1 hr pre-incubation time is evaluated. SARS-CoV-2 RNA Ct values are determined in cell culture supernatant by qRT-PCR at 48 hrs after infection. The results are shown in FIG. 3. The qRT-PCR results in six technical replicas with BanLec in mean Ct values 29.63. Compared to the six positive controls with a mean Ct value of 17.15 an approximately 5.8*103-fold reduction in virus concentration is achieved.

SEQUENCE LISTING

[0270] <210> SEQ ID NO:

[0271] <211> 227

[0272] <212> PRT

[0273] <213> human

[0274] <400>

[0275] Glu Thr Val Thr Cys Glu Asp Ala Gln Lys Thr Cys Pro Ala Val Ile

[0276] 1 5 10 15

[0277] Ala Cys Ser Ser Pro Gly Ile Asn Phe Pro Gly Lys Asp Gly Arg [0278] 20 25 30

[0279] Asp Gly Thr Lys Gly Glu Lys Gly Glu Pro Gly Gln Gly Leu Arg Gly [0280] 35 40 45

[0281] Leu Gln Gly Pro Pro Gly Lys Leu Gly Pro Pro Gly Asn Pro Gly Pro [0282] 50 55 60

[0283] Ser Gly Ser Pro Gly Pro Lys Gly Gln Lys Gly Asp Pro Gly Lys Ser

[0284] 65 70 75 80

[0285] Pro Asp gly Asp Ser Leu Ala Ala Ser Glu Arg Lys Ala Leu Gln  85 90 95

[0286] Thr Glu Met Arg Ile Lys Lys Trp Leu Thr Phe Ser Leu Gly Lys  100 105 110

[0287] Gln Val Gly Asn Lys Phe Phe Leu Thr Asn Gly Glu Ile Met Thr Phe [0288] 115 120 125

[0289] Glu Lys Val Lys Ala Leu Cys Val Lys Phe Gln Ala Ser Val Ala Thr [0290] 130 135 140

[0291] Pro Arg Asn Ala Ala Glu Asn Gly Ala Ile Gln Asn Leu Ile Lys Glu [0292] 145 150 155

[0293] Glu Ala Phe Leu Gly Ile Thr Asp Glu Lys Thr Glu Gly Gln Phe Val

[0294] 160 165 170 175

[0295] Asp Leu Thr Gly Asn Arg Leu Thr Tyr Thr Asn Trp Asn Glu Gly Glu [0296] 180 185 190

[0297] Pro Asn Asn Ala Gly Ser Asp Glu Asp Cys Val Leu Leo Leu Lys Asn [0298] 195 200 205

[0299] Gly Gln Trp Asn Asp Val Pro Cys Ser Thr Ser His Leu Leu Ala Val Cys [0300] 210 215 220

[0301] Glu Phe Pro ile [0302] 225

[0303] <210> SEQ ID NO: 2

[0304] <211> 112

[0305] <212> PRT

[0306] <213> human

[0307] <400>

[0308] Val Gly Asn Lys Phe Phe Leu Thr Asn Gly Glu Ile Met Thr

[0309] 1 5 10

[0310] Phe Glu Lys Val Lys Ala Leu Cys Val Lys Phe Gln Ala Ser

[0311] 15 20 25

[0312] Val Ala Thr Pro Arg Asn Ala Ala Glu Asn Gly Ala Ile Gln [0313] 30 35 40

[0314] Asn Leu Ile Lys Glu Glu Ala Phe Leu Gly Ile Thr Asp Glu [0315] 45 50 55

[0316] Lys Thr Glu Gly Gln Phe Val Asp Leu Thr Gly Asn Arg Leu [0317] 60 65 70

[0318] Thr Tyr Thr Asn Trp Asn Glu Gly Glu Pro Asn Asn Ala Gly [0319] 75 80

[0320] Ser Asp Glu Asp Cys Val Leu Leu Leu Lys Asn Gly Gln Trp

[0321] 85 90 95

[0322] Asn Asp Val Pro Cys Ser Thr Per His Leu Ala Val Cys Glu [0323] 100 105 110

[0324] <210> SEQ ID NO: 3

[0325] <211> 17

[0326] <212> PRT

[0327] <213> human

[0328] <400>

[0329] Glu Arg Lys Ala Leu Gln Thr Glu Met Ala Arg Ile Lys Lys

[0330] 1 5 10

[0331] Trp Leu Thr Phe [0332] 15