Methods and compositions for antiviral use of synthetic lysine analogs and mimetics

Abstract

To provide methods and compositions for the treatment, prevention, or reduction of one-time or recurring viral outbreaks, for suppression of development or growth of chronic viral infections, or for prevention or treatment of viral infections.SOLUTION: Provided is a method including administering a synthetic lysine analog or mimetic, the synthetic lysine analog or mimetic antagonizing or competing with an amino acid or other biological agent required by a virus to replicate or spread. Additionally, provided is a composition to treat, prevent, or reduce one-time or recurrent viral outbreaks, suppress development or growth of chronic viral infections, or to prevent or treat viral infections, the composition including, a synthetic lysine analog or mimetic, and the synthetic lysine analog or mimetic antagonizing or competing with an amino acid or other biological agent required by a virus to replicate or spread.SELECTED DRAWING: None

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This patent application claims priority to U.S. Provisional Patent Application No. 62 / 550,656, filed August 27, 2017, and U.S. Provisional Patent Application No. 62 / 664,555, filed April 30, 2018, the disclosures of which are incorporated by reference in their entireties.

[0002] The present disclosure relates generally to lysine analogs and mimetics, and more particularly, but not exclusively, to methods and compositions for the antiviral use of synthetic lysine analogs and mimetics. [Background technology]

[0003] Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are highly prevalent in the human population, with various estimates suggesting that up to 80% of the world's population is carrier of HSV-1. Similarly, the Centers for Disease Control and Prevention estimates that approximately 99.5% of people born in the United States aged 40 or older are infected with wild-type varicella-zoster virus (VZV). In addition to HSV-1, HSV-2, and VZV, approximately 36.7 million people are currently estimated to be living with human immunodeficiency virus (HIV). While many people worldwide are affected by HSV-1, HSV-2, VZV, and HIV, cold and influenza viruses are even more prominent and can have serious or life-threatening effects on various age groups or susceptible populations. One approach to treatment is the use of antiviral drugs, but some antiviral drugs have shown limitations in that they are ineffective in treating, preventing, and suppressing HSV-1, HSV-2, VZV, HIV, or cold and influenza viruses. Summary of the Invention

[0004] A method for treating, preventing, or reducing transient or recurrent viral outbreaks, for inhibiting the onset or growth of a chronic viral infection, or for preventing or treating a viral infection, comprising administering a synthetic lysine analog or mimetic that antagonizes or competes with an amino acid or other biological agent required for viral replication or spread.

[0005] A composition for treating, preventing, or reducing transient or recurrent viral outbreaks, for inhibiting the onset or growth of a chronic viral infection, or for preventing or treating a viral infection, the composition comprising a synthetic lysine analog or mimetic that antagonizes or competes with an amino acid or other biological agent required for viral replication or spread. DETAILED DESCRIPTION OF THE INVENTION

[0006] Examples of viruses that chronically persist in the human body and exhibit recurrent outbreaks are herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2), which are highly prevalent in the human population. HSV-1 is typically associated with herpes labialis, or recurrent herpes labialis (RHL), although HSV-2 may also be involved. HSV-2 is typically associated with genital herpes, although HSV-1 may also be involved. HSV-1 is more prevalent, and various estimates suggest that, due to its highly contagious nature, up to 80% of the world's population carries the HSV-1 virus, and 40% of the world's population periodically experiences recurrent RHL outbreaks. In the case of RHL, there are usually no signs that a person is carrying the herpes virus until an outbreak occurs, typically affecting the lips or areas near the mouth. Visible outbreaks can take the form of sores, which can be inflamed, raw, and painful. The course of the viral outbreak and its associated visible lesions usually resolves completely within about two to four weeks through the body's natural healing processes without medical treatment.

[0007] Current treatments designed to reduce the severity and duration of these outbreaks consist primarily of antiviral medications, such as the oral treatment VALTREX® and the ointment ABREVA®. While these treatments have been shown to be somewhat effective, they typically result in visible sores and symptoms for up to two weeks, even when targeted at the first signs of an outbreak. With regard to recurrences, as opposed to severity or healing time, a 2016 Cochrane review found that oral antiviral medications offer limited clinical benefit, and topical antivirals or any other treatments are ineffective or have no proven efficacy.

[0008] Based on studies measuring viral growth when various amino acids were omitted from the culture medium, studies suggest that histidine and arginine, in that order, are the two most important of the 11 amino acids required for HSV-1 viral replication. Furthermore, lysine is not required for viral replication and has actually shown an inhibitory effect on viral growth. Other studies have shown that increasing the predominance of lysine relative to arginine in the body can suppress viral replication. Therefore, for example, taking lysine supplements or administering creams or ointments containing lysine may reduce the severity and duration of herpes outbreaks by changing one's diet to reduce arginine-rich foods and increase lysine-rich foods. Furthermore, long-term changes in diet or supplementation may reduce the incidence of HSV-1 outbreaks. Therefore, various lysine nutritional supplement products are commercially available. However, from 1975 to 1987, only five studies, primarily double-blind, placebo-controlled, parallel, or crossover studies, were conducted on oral lysine supplementation. Three of the studies found that long-term daily lysine supplementation reduced outbreak severity and recurrence, while one found it reduced recurrence only, and one found no benefit in either severity or recurrence.Currently, the main treatments usually recommended by doctors for symptomatic outbreaks are oral and topical antiviral medications.

[0009] Additionally, there are several topical creams and ointments containing lysine, such as SUPERLYSINE+™ Cold Sore Treatment, which promise to reduce healing time by half by relieving pain, helping to stop burning and itching, and moisturizing the infected area. However, in this product, the active ingredient is menthol, and the amino acid L-lysine is listed as an inactive ingredient, along with various plant extracts, vitamins, and zinc oxide. Additionally, even if healing time is halved, outbreaks can still occur for one to two weeks. A clinical study supporting this product showed that nearly half of 30 subjects were not cured by the fourth day, and all 30 subjects took 11 days to heal.

[0010] Due to the commonality of HSV-1, further research is being conducted to identify and better understand its interactions in the body to facilitate treatment and suppress recurrence. In vitro studies have shown that HSV-1 has amino acid nutritional requirements, and as briefly discussed above, lysine, histidine, and arginine, in particular, play important roles in herpesvirus replication. However, histidine deficiency resulted in significant cytopathic effects, so further research was not conducted. Subsequent research focused on antagonizing arginine to achieve viral inhibition without cytotoxicity.

[0011] It has been demonstrated that the addition of arginine to HSV-1 cultures maintains optimal HSV-1 viral growth levels, and furthermore, that HSV-1 is dependent on arginine for growth. Studies have reported that HSV-1 does not grow in culture media without arginine. In arginine-deficient media, HSV-1 exhibits inhibition of virion synthesis, reduced protein synthesis, and inhibition of viral peptide transport from the cytoplasm to the nucleus. This indicates promising results for enhancing both the treatment and prevention of recurrence by relying on arginine dependency for replication.

[0012] Studies have shown that in arginine-deficient media, HSV-1 envelope polypeptide (II) is transported very slowly from the cytoplasm to the nucleus. Polypeptide (VII) is an arginine-rich protein whose synthesis is arginine-dependent. Without arginine, most viral structural proteins, especially viral capsid polypeptide II, remain in the cytoplasm. Additionally, HSV-1 DNA in the nucleus is uncoated and unable to replicate. Residual viral proteins in the cytoplasm are rapidly degraded.

[0013] Various studies have been conducted to verify that arginine supports HSV-1 replication and that lysine antagonizes this effect in vitro. The action of lysine appears to be multifactorial. One mechanism appears to involve the histone layer surrounding the DNA of the host eukaryotic cell. Five different types of histones have been identified, which are synthesized exclusively during DNA replication, where lysine-rich histones crosslink chromatin DNA fibrils during metaphase and interphase, making chromatin more compact and thus maintaining the structural integrity of human chromosomes. The DNA nucleoside composition of HSV-1 contains a high ratio of arginine to lysine, and infected cells synthesize proteins with a high ratio of arginine to lysine. HSV-1 frequently utilizes guanine (G)-containing codons, whereas human host cells utilize cytosine (C)-guanine less frequently. There are six arginine codons and only two lysine codons. A simple shift of one nucleotide produces arginine. This can occur very rapidly within the translational apparatus of the infected host cell: lysine-rich host cell proteins are modified by the viral DNA, and new arginyl tRNAs are synthesized to produce arginine-rich proteins.

[0014] Studies suggest that lysine also appears to be an antimetabolite and analog of arginine, competing for renal tubular reabsorption, leading to increased excretion of arginine, competing for transport across the intestinal wall, acting as an arginase inducer, leading to the degradation of arginine, and reducing the intracellular content of arginine in tissue cells by entering the transport system.

[0015] In addition to in vitro studies, several clinical trials have been conducted, which suggest that when taken in appropriate doses and under appropriate conditions (e.g., controlling the amount of arginine-containing foods consumed), lysine taken orally over a long period of time can successfully reduce the recurrence of herpes outbreaks. However, this line of research was terminated, likely due to concerns that continued intake of natural lysine may result in undesirable side effects. Therefore, it may be beneficial to use synthetic (artificial) lysine analogs or mimetics, including locally delivered lysine analogs or mimetics, to mimic the antiviral effects of lysine or to enhance the effects of natural lysine against herpes viruses, so as to directly affect the relevant tissues and reduce systemic effects.

[0016] As detailed above, oral and topical lysine treatments have been shown to provide limited benefit, and primary physician-directed treatment with oral and topical antiviral medications has also shown limited effectiveness in reducing the severity, duration, and recurrence of HSV-1 outbreaks. However, in light of the above-mentioned investigations and studies, therapeutic treatment with antiviral agents that more significantly reduce the severity and duration of HSV-1 outbreaks may prove beneficial. Furthermore, utilizing the information gained from the various studies detailed above, long-term or prophylactic use of antiviral medications to avoid recurrence of HSV-1 outbreaks may prove even more beneficial.

[0017] In addition to treating and suppressing recurrence of HSV-1 outbreaks, lysine and its analogs or derivatives may prove beneficial for prophylactic use in other viral infections, such as human immunodeficiency virus (HIV), influenza virus, and cold viruses, among others. HIV is an example of a virus that persists chronically in the human body, not exhibiting outbreaks, but which develops over time and causes serious adverse effects. Continuing replication of the HIV virus ultimately destroys the immune system and predisposes the body to other life-threatening diseases. Studies have shown that, unlike herpes viruses, HIV requires lysine for replication, and adding lysine to the plasma of HIV-infected patients rapidly increased viral replication. Adding arginine, on the other hand, had no effect. It is believed that synthetic lysine analogs or mimetics can be used to inhibit HIV replication by competing with (blocking) the activity of natural lysine, and the in vitro studies described below appear to support this effect.

[0018] Furthermore, the long-term or preventive use of antiviral agents to avoid infection is beneficial, and may include, for example, influenza virus, cold virus, or other transient viruses, and may be particularly advantageous for subjects who are at increased risk of being exposed to infectious diseases, such as teachers or travelers, and for individuals who are at high risk of becoming seriously ill from infectious diseases, such as the elderly or young children.Natural medicine literature has shown that lysine supplementation is beneficial for treating and avoiding influenza virus and cold virus.Therefore, the use of antiviral agents to treat infectious diseases may also prove beneficial, and may include, for example, treating influenza virus, cold virus, or other transient viruses.

[0019] In view of the above, synthetic lysine analogs or mimetics are potentially useful in treating viruses such as herpes viruses, inhibiting recurrence of outbreaks of viruses such as herpes viruses, inhibiting the development of viruses such as HIV, and preventing or treating infections by viruses such as influenza and cold viruses or other transient viruses, where the lysine analog or mimetic mimics and enhances the effects of lysine in antagonizing other amino acids required for viral replication, or competes with and blocks natural lysine when required for viral replication. In addition, because antiviral synthetic lysine analogs or mimetics act at the fundamental level of an amino acid that is a fundamental building block of all proteins and certain other metabolic activities, they are far less likely to be affected by viral resistance (e.g., mutations surrounding the drug's activity) than conventional antiviral drugs that act on specific proteins or their activities.

[0020] The disclosure herein utilizes the pharmacology of synthetic lysine analogs or mimetics to antagonize amino acids required for the replication of certain viruses or to compete with natural lysines when required for viral replication. The disclosure includes methods and compositions for minimizing the severity and duration of herpes virus outbreaks and for treating infections with certain frequently transmitted viruses, such as cold and influenza viruses or other transient viruses, using synthetic lysine analogs or mimetics. Furthermore, the disclosure includes methods and compositions for the prophylactic use of synthetic lysine analogs or mimetics for the prevention or reduction of the incidence of outbreaks of viruses that chronically persist in the human body, such as HSV-1 and HSV-2, which are involved in outbreaks of herpes labialis and genital herpes, inhibiting the development and proliferation of viruses that chronically persist in the human body and continue to replicate and develop over time with increasingly negative consequences, such as HIV, and for the prevention of infections with certain frequently transmitted viruses, such as cold and influenza viruses or other transient viruses.

[0021] Based on studies and research showing that the amino acid lysine is important for the replication of certain viruses and that lysine supplementation can antagonize or block the activity of other amino acids necessary for the replication of certain viruses, as well as knowledge of how synthetic lysine analogs or mimetics can mimic in some cases and compete with natural lysine in other cases, the present disclosure includes methods and compositions for the chronic or prophylactic use of synthetic lysine analogs or mimetics to inhibit viral replication, thereby reducing the incidence of recurrent outbreaks of certain viruses, such as HSV-1 and HSV-2, suppressing the development of other chronic viruses, such as HIV, and avoiding infection by certain viruses, such as influenza and cold viruses, or other transient viruses.

[0022] In some embodiments, the synthetic lysine analog can be tranexamic acid. In various embodiments, the synthetic lysine analog can be epsilon-aminocaproic acid (EACA). In other embodiments, various agents can be utilized, such as lysine mimetics, e.g., AZD6564, or any other compound that replicates or mimics the function of lysine by treating, preventing, or reducing viral outbreaks, inhibiting the onset or growth of chronic viral infections, or preventing or treating viral infections in the same manner as synthetic lysine analogs such as tranexamic acid.

[0023] Laboratory tests, described in more detail below, suggest that at least one synthetic lysine analog, tranexamic acid, is effective in inhibiting the replication of HSV-1 and HSV-2. Additionally, as described in more detail below, laboratory tests suggest that adding tranexamic acid to cells infected with HIV inhibited viral replication. Thus, in the case of this virus, tranexamic acid apparently competes with natural lysines, i.e., blocks lysines from normal use, through a viral replication mechanism similar to tranexamic acid's antifibrinolytic effect (by competing with natural lysines by occupying their normal binding site on plasminogen, thereby preventing plasminogen from being converted to plasmin).

[0024] Additionally, laboratory tests suggest that tranexamic acid is effective in inhibiting influenza A virus (H3N2) replication, demonstrating its distinct antiviral function. Further laboratory tests suggest that an excess of one of three basic amino acids (lysine, arginine, histidine, or their analogs or mimetics) inhibits the activity of the other two, and that an excess of two of them in combination has the same effect on the third, even allowing for larger doses of the combination without cytotoxicity. As discussed in more detail below, adding arginine and tranexamic acid at levels just below cytotoxicity resulted in the highest levels of viral inhibition for herpesviruses, whereas adding the same amount of tranexamic acid alone resulted in substantially lower inhibition, and adding the same amount of arginine alone increased viral replication.

[0025] While research has shown that lysine antagonizes arginine, previous studies have suggested that histidine is a key amino acid involved in herpes replication. Based on this study and observed laboratory results, it is believed that an excess of one basic (non-acidic) amino acid or its analog or mimic of one of the three basic amino acids may antagonize the other two basic amino acids. Furthermore, an excess of two basic amino acids or their analogs or mimics may antagonize the third basic amino acid. The laboratory results discussed below suggest that, given sufficient amounts, tranexamic acid antagonizes arginine and histidine, while the combination of tranexamic acid and arginine antagonizes histidine, and the combination of tranexamic acid and histidine antagonizes arginine.

[0026] Based on the laboratory testing discussed in detail below, and the research and studies presented above, it is an object of the present disclosure to provide methods and compositions for minimizing the severity and duration of herpes virus outbreaks. According to the present disclosure, as soon as the first sign of an outbreak is recognized, a therapeutically safe and effective amount of a synthetic lysine analog or mimetic is made available to the infected area and continued until the outbreak has adequately subsided, for example, for 1 to 14 days.

[0027] Another object of the present disclosure is to provide methods and compositions for preventing viral outbreaks, such as RHL (Herpes Labialis) outbreaks. According to the present disclosure, therapeutically safe and effective amounts of synthetic lysine analogs or mimetics may be available for repeated administration for prophylactic use.

[0028] Both therapeutic and prophylactic uses can be achieved by systemic administration of the drug, for example, orally, but it is also contemplated that topical application is also possible at effective concentrations and regimens. In certain variations of the present disclosure, the synthetic lysine analogs include tranexamic acid, which antagonizes arginine and histidine and has been specifically shown to inhibit the replication of HSV-1 and HSV-2 viruses. In another variation of the present disclosure, the synthetic lysine analogs include a combination of tranexamic acid and arginine, which antagonizes histidine and has been specifically shown to inhibit the replication of HSV-1 and HSV-2 viruses. In some embodiments, compositions and methods of use thereof can include synthetic lysine analogs or mimetics in combination with one or more amino acids to treat, prevent, or reduce outbreaks of recurrent viruses such as herpes viruses, to inhibit the onset or growth of chronic viral infections such as HIV, or to prevent or treat infections with viruses such as influenza and cold viruses or other transient viruses.

[0029] Furthermore, it is believed that synthetic lysine analogs and mimetics can be used to inhibit the replication of viruses that chronically persist in the body and continue to develop over time, such as HIV. Therefore, another object of the present disclosure is to provide a therapeutically safe and effective amount of a synthetic lysine analog or mimetic that may be available for repeated administration for prophylactic use to suppress HIV viral replication and development. While the mechanism for inhibiting HSV-1 and HSV-2 is different, it is believed that tranexamic acid competes with and replaces the natural lysine required by HIV for replication, similar to how tranexamic acid prevents plasminogen from activating to plasmin (e.g., by occupying the lysine-binding site on plasminogen), rather than antagonizing the arginine and histidine required by HSV-1 and HSV-2 for replication.

[0030] Furthermore, it is believed that synthetic lysine analogs or mimetics can be utilized to avoid or reduce the severity of infection by certain viruses, such as influenza and cold viruses, or other transient viruses, for example, by administering the agent to individuals who have increased exposure to the infection or who are at increased risk of serious consequences from the infection. In addition, it is believed that synthetic lysine analogs or mimetics can be used to treat infection by certain viruses, such as influenza and cold viruses, or other transient viruses. It is understood that all of these uses of synthetic lysine analogs or mimetics can be used in combination with other antiviral therapeutic agents, where appropriate.

[0031] Furthermore, due to the inhibitory properties of synthetic lysine analogs or mimetics against viruses such as herpesviruses, it is further anticipated that synthetic lysine analogs or mimetics could be used to promote the prevention, slow the progression, and potentially treat (or be used in combination with other treatments) of Alzheimer's disease. Recent research suggests that two very common herpesviruses affect the behavior of genes involved in Alzheimer's disease. Evidence suggests that the brain actively defends itself against viruses and other bacteria, and experiments have shown that sticky beta-amyloid traps invading bacteria by engulfing them, which is why plaques begin to form. One of the hallmarks of Alzheimer's disease is the accumulation of amyloid plaques between neurons in the brain. Amyloid is a collective term for protein fragments normally produced by the body. Beta-amyloid is a protein fragment cleaved from the amyloid precursor protein. In a healthy brain, these protein fragments are broken down and removed, but in Alzheimer's disease, the fragments accumulate and form hard, insoluble plaques. Certain experiments have shown that amyloid plaques form more readily in the absence of molecules that deplete herpes (in this case, human herpesvirus 6A (HHV6a) and human herpesvirus 7 (HHV7)). This suggests a relationship between viruses and Alzheimer's disease. Furthermore, it is believed that HHV6 and the herpesviruses that cause cold sores may induce or contribute to the formation of amyloid plaques. Therefore, the methods and compositions presented herein for treating and suppressing recurrent herpes outbreaks may prove beneficial as potential prevention or treatments for, or slowing the progression of, Alzheimer's disease. It is understood that these uses of synthetic lysine analogs or mimetics can be used in combination with other regimens and treatments for Alzheimer's disease, where appropriate.

[0032] Virus inhibition by amino acids normally required for uninfected cultured cells is not uncommon. For example, lysine has also been shown to inhibit GD VII murine encephalomyelitis virus. Glycine has been shown to inhibit poliovirus replication in monkey kidney cells, where glycine is a required amino acid. Similarly, glutamine is required for continued herpesvirus replication, and under certain conditions, glutamine has actually had an effect on reducing virus yield. Other studies have shown that adding arginine in sufficient amounts and under certain conditions inhibits HSV-1. Arginine also inhibited influenza A (H3N2) and poliovirus type 1. Thus, adding arginine, glutamine, or other amino acids to compositions containing tranexamic acid or other synthetic lysine analogs or mimetics may be useful for treating, preventing, or reducing outbreaks of transient or recurrent viruses such as herpesviruses, suppressing the onset or growth of chronic viral infections such as HIV, or preventing or treating infections with viruses such as influenza and cold viruses or other transient viruses.

[0033] More specific embodiments of the present disclosure, as well as data providing support for such embodiments, will now be described. It should be noted, however, that the following disclosure is for illustrative purposes only and is not intended to limit the scope of the claimed subject matter in any way.

[0034] Embodiments of the present disclosure relate to the application of synthetic lysine analogs or mimetics to exploit the pharmacological activity of the agent / composition and its effect on visible outbreaks, resulting in rapid healing and restoration of normal cosmetic appearance. The synthetic lysine analogs or mimetics can be in the form of a simple aqueous solution, a solution containing inert excipients, or combined with a vehicle such as a gel, cream, or lotion, which may optionally contain other therapeutic ingredients. Additional embodiments for improving handling or therapeutic delivery, such as via a viscous solution or via a solution designed for delayed or slow / predictable delivery of the synthetic lysine analog or mimetic, are anticipated and will be known by those skilled in the art. The solution / composition can be administered directly to the skin area showing signs of an outbreak, is easily applied, and will easily dissolve into the affected area. In some embodiments, the composition exploits the activity of the agent / composition at the first sign of a viral outbreak to reduce the severity and duration of the outbreak and promote a rapid healing process.

[0035] In certain embodiments, synthetic lysine analog or mimetic treatment can be performed by systemic administration of the drug, for example, up to 4 grams per day for 7 days, but can also be applied topically at an effective concentration and regimen, for example, at a concentration of 3 to 5% (w / v) in a volume of 0.25 to 5 mL two to three times per day, to provide rapid activity and benefit. In some embodiments, the drug concentration can be, for example, up to 30% (w / v). In various embodiments, the lysine analog or mimetic can inhibit HSV-1 viral replication by competing with arginine and histidine, and can maintain the amount of natural lysine in the area by not being able to bind plasminogen to generate plasmin that would otherwise occur in association with trauma to the tissue, blocking the formation of plasmin and serine proteases, thereby providing an anti-inflammatory effect and preventing the degradation of collagen and the collagen matrix.

[0036] Furthermore, embodiments of the present disclosure are directed to the application of synthetic lysine analogs or mimetics to provide prophylaxis against viral outbreaks by utilizing the pharmacological activity of the agent / composition. The agent may be a simple aqueous solution, a solution containing inert excipients, or a combination with a vehicle such as a gel, cream, or lotion, which may optionally contain other therapeutic ingredients. Additional embodiments that improve handling and / or prophylactic delivery, such as via a viscous solution or via a solution designed for delayed or predictable delivery of the synthetic lysine analog or mimetic, are also anticipated and known by those skilled in the art. The solution and / or composition can be administered directly to areas of the skin where outbreaks are known to occur, is easily applied, and will easily dissolve in the desired area of ​​application. In some embodiments, the solution and / or composition may be at a concentration of 3 to 10% (w / v) of the synthetic lysine analog or mimetic, or up to 30% (w / v) of the synthetic lysine analog or mimetic.

[0037] In some embodiments, the compositions can be used to prevent or treat infections and diseases caused by other viruses, including, but not limited to, common cold viruses and influenza viruses or other transient viruses, for example, in individuals at high risk of exposure, or individuals who have been exposed to infection with such viruses but have not yet shown symptoms of infection, or individuals in whom infection with such viruses may present a life-threatening event. Because some of these viruses adhere to the back of the throat and nasal passages, in some embodiments, the compositions can be formulated into sprays, mists, aerosols, and mouthwashes or swabs that can be applied to the mouth, nose, and / or throat area, including the nasal passages. In some embodiments, the solutions and / or compositions can have a concentration of 3 to 10% (w / v) of the synthetic lysine analog or mimetic, or up to 30% (w / v) of the synthetic lysine analog or mimetic.

[0038] In other embodiments, the compositions provided herein can be used to prevent viral outbreaks or inhibit the onset of viral infections and can be administered enterally and parenterally, for example, via pills, tablets, capsules, or injections. In further embodiments, the compositions can be administered via injection or implanted liposome delivery depots for long-term administration. In some embodiments, the compositions can be in the form of a transdermal patch that administers the drug via skin contact.

[0039] Additionally, some embodiments of the present disclosure are directed to compositions and methods of using synthetic lysine analogs or mimetics in combination with arginine to treat and prevent viral outbreaks, such as herpes viruses, inhibit the development of other chronic viruses, such as HIV, and aid in avoiding or treating infections with certain viruses, such as influenza and cold viruses, or other transient viruses, by utilizing the pharmacological activity of the combination of excess amounts of lysine analogs or mimetics with arginine. In some embodiments, other amino acids necessary to construct proteins required for viral replication can be used in combination with the synthetic lysine analogs or mimetics, such as tranexamic acid, to improve the antiviral function of the synthetic lysine analogs or mimetics.

[0040] Furthermore, various embodiments of the present disclosure are directed to compositions and methods of using synthetic lysine analogs or mimetics in combination with one or more amino acids, such as synthetic lysine analogs combining tranexamic acid with lysine, arginine, or histidine, for the treatment and prevention of viral outbreaks, such as herpes viruses, the suppression of the onset of other chronic viruses, such as HIV, and the avoidance or treatment of infection with certain viruses, such as influenza and cold viruses, or other transient viruses. In various embodiments, the synthetic lysine analogs or mimetics can be used in combination with one or more synthetic amino acids, analogs, or mimetics thereof, for the treatment and prevention of viral outbreaks, the suppression of the onset of other chronic viruses, such as HIV, and the avoidance or treatment of infection with certain viruses, such as influenza and cold viruses, or other transient viruses.

[0041] In some embodiments, synthetic lysine analogs or mimetics can be combined with one or more or combinations of any amino acid (e.g., aliphatic, aromatic, acidic, basic, neutral, or unique amino acids) for the treatment and prevention of viral outbreaks such as herpes viruses, suppression of the development of other chronic viruses such as HIV, and avoidance or treatment of infection with certain viruses, such as influenza and cold viruses, or other transient viruses.

[0042] In various embodiments, the present disclosure is directed to compositions and methods of use of synthetic lysine analogs or mimetics in combination with glutamine for treating, preventing, or reducing outbreaks of recurrent viruses such as herpes viruses, inhibiting the onset or growth of infections with chronic viruses such as HIV, or preventing or treating infections with viruses such as influenza and cold viruses or other transient viruses. In certain embodiments, the compositions can include tranexamic acid and glutamine. In other embodiments, the compositions can include tranexamic acid, glutamine, and one or more amino acids such as lysine, arginine, or histidine.

[0043] Antiviral activity of tranexamic acid The antiviral activity of tranexamic acid, i.e., the reduction of viral replication, was evaluated for HSV-1, HSV-2, HIV, and influenza A virus (H3N2). Each evaluation was performed using high and low virus inoculations, and Log 10 It consisted of an input virus control (without tranexamic acid) used for input virus titer determination of reduction and corresponding percentage replication reduction.

[0044] Additionally, the antiviral activity of 2% (w / v) tranexamic acid, L-arginine (at various concentrations), and a mixture of 2% (w / v) tranexamic acid and L-arginine (at various concentrations) was evaluated against HSV-1 and HSV-2 to demonstrate the effect of the combination of tranexamic acid and L-arginine on viral reduction rates and to identify how tranexamic acid inhibits HSV-1 and HSV-2 replication. Each evaluation consisted of an input virus control (no excess tranexamic acid or L-arginine) that was used as the input viral titer when determining replication reduction rates.

[0045] As discussed in more detail below, 0.5% (w / v), 1.0% (w / v), and 2.0% (w / v) tranexamic acid were used to evaluate the replication reduction of HSV-1 and HSV-2, while 2.0% (w / v), 3.0% (w / v), and 4.0% (w / v) tranexamic acid were used to evaluate the replication reduction of HIV based on the cytotoxicity limits of the cell culture medium for the two different types of viruses. 6% (w / v), 8% (w / v), and 10% (w / v) tranexamic acid were used to evaluate the replication reduction of H3N2.

[0046] As described in more detail below, evaluation of 5,000 μM, 10,000 μM, and 25,000 μM L-arginine on HSV-1 and HSV-2 contrasted with evaluation of 2% (w / v) tranexamic acid and 5,000 μM L-arginine, 2% (w / v) tranexamic acid and 10,000 μM L-arginine, and 2% (w / v) tranexamic acid and 25,000 μM L-arginine on HSV-1 and HSV-2, demonstrating the underlying mechanism of action of tranexamic acid in inhibiting HSV-1 and HSV-2 replication and demonstrating the enhanced efficacy of the combined mixture of tranexamic acid and L-arginine in reducing viral load.

[0047] As described in more detail below, various concentrations of L-arginine, various concentrations of L-histidine, combinations of 2% (w / v) tranexamic acid with various concentrations of L-arginine, combinations of 2% (w / v) tranexamic acid with various concentrations of L-histidine, and combinations of 2% (w / v) tranexamic acid with various concentrations of L-arginine and L-histidine were evaluated using HSV-1, and it was confirmed that tranexamic acid antagonized arginine and histidine, while at sufficient amounts, a mixture of tranexamic acid and arginine antagonized histidine, and a mixture of tranexamic acid and histidine antagonized arginine. Essentially, as shown below, the addition of one or more amino acids to tranexamic acid can significantly improve the effectiveness of its antiviral activity. This improved efficacy is achieved by having an excess of amino acids that compete with other amino acids (eg, the combination of tranexamic acid and arginine, which acts as lysine to compete with histidine).

[0048] Antiviral activity of tranexamic acid against herpes simplex virus type 1 (HSV-1) Each sample tested below was replicated three times and consisted of an input virus control of 0% (w / v) tranexamic acid, 0.5% (w / v), 1.0% (w / v), and 2.0% (w / v) tranexamic acid for low and high virus inocula. The contact time for each sample was 48±8 hours, and the input virus titer (Log 10 TCID 50 ) and output virus titer (Log 10 TCID 50 ) to generate the reduction factor, resulting in Log 10 The reduction coefficient and correlation reduction rate were obtained.

[0049] A preparation to evaluate the antiviral activity of tranexamic acid against HSV-1 for a low virus inoculum was prepared as follows: 0.25 mL of virus inoculum (10 6.26 TCID 50 Units) were added to triplicate wells for each dose of tranexamic acid or input virus control. The inoculum was incubated for 90 minutes at 36±2°C with 5±3% CO2. The inoculum was removed, and the wells were washed three times with PBS. 1.0 mL of each dose of tranexamic acid (or DM for input virus control) was added to each well. The plates were incubated for 48±8 hours at 36±2°C with 5±3% CO2. The plates were then frozen overnight at -60 to -90°C, thawed, and the contents of each well were centrifuged at 2,000 RPM for 10 minutes. The supernatant from each well was collected and assayed for infectious virus.

[0050] The titer results are shown in Table 1 below and are the input virus control titers (Log 10 TCID 50 / mL) ranged from 5.95±0.10 to 6.55±0.10 with a mean of 6.26±0.10, and the virus strain titer control had a titer of 2.30±0.19. 10 TCID 50 Sample amounts of 0.5% (w / v), 1.0% (w / v), and 2.0% (w / v) tranexamic acid with a concentration of 0.5% (w / v), 1.0% (w / v), and 2.0% (w / v) were used in the study. TIFF2025166032000001.tif130170

[0051] Preparations for evaluation of the antiviral activity of tranexamic acid against HSV-1 for high virus inocula were prepared as follows: 0.25 mL of virus inoculum (10 6.46 TCID 50 Units) were added to triplicate wells for each dose of tranexamic acid or input virus control. The inoculum was incubated for 90 minutes at 36±2°C with 5±3% CO2. The inoculum was removed, and the wells were washed three times with PBS. 1.0 mL of each dose of tranexamic acid (or DM for input virus control) was added to each well. The plates were incubated for 48±8 hours at 36±2°C with 5±3% CO2. The plates were then frozen overnight at -60 to -90°C, thawed, and the contents of each well were centrifuged at 2,000 RPM for 10 minutes. The supernatant from each well was collected and assayed for infectious virus.

[0052] The titer results are shown in Table 2 below and represent the input virus control titers (Log 10 TCID 50 / mL) ranged from 6.37±0.13 to 6.55±0.14 with a mean of 6.46±0.13, and the virus strain titer control had a titer of 2.30±0.19. 10 TCID 50 Sample amounts of 0.5% (w / v), 1.0% (w / v), and 2.0% (w / v) tranexamic acid with a concentration of 0.5% (w / v), 1.0% (w / v), and 2.0% (w / v) were used in the study. TIFF2025166032000002.tif130170

[0053] Using the average of the input virus controls as the input virus titer, the resulting reduction factors are shown in Table 3 below. As can be seen in Table 3, the reduction rates were greatest at low virus inocula of 90.5% (w / v) tranexamic acid, 98.8% (w / v) tranexamic acid, and 99.7% (w / v) tranexamic acid. The data show that at low virus inocula, as expected, the reduction rate increased with increasing tranexamic acid percentage; at high virus inocula, an increasing reduction rate was observed between 0.5% (w / v) and 2.0% (w / v) tranexamic acid percentages. At high virus inoculum levels, reductions were greatest at 45.9% with 0.5% (w / v), 5.9% with 1.0% (w / v), and 90.8% with 2.0% (w / v). The reductions at 2.0% (w / v) tranexamic acid are particularly noteworthy, as suggested by the low virus inoculum, which showed a reduction of over 99%. Because the level of viral infection is likely relatively low before an outbreak, the effectiveness of tranexamic acid at this level is more relevant to outbreak control. TIFF2025166032000003.tif146170

[0054] Antiviral activity of tranexamic acid against herpes simplex virus type 2 (HSV-2) Each sample tested below was replicated three times and consisted of an input virus control of 0% (w / v) tranexamic acid, 0.5% (w / v), 1.0% (w / v), and 2.0% (w / v) tranexamic acid for low and high virus inocula. The contact time for each sample was 48±8 hours, and the input virus titer (Log 10 TCID 50 ) and output virus titer (Log 10 TCID 50 ) to generate the reduction factor, resulting in Log 10 The reduction coefficient and correlation reduction rate were obtained.

[0055] Preparations for evaluation of the antiviral activity of tranexamic acid against HSV-2 for low virus inocula were prepared as follows: 0.25 mL of virus inoculum (10 2.1 TCID 50 Units) were added to triplicate wells for each dose of tranexamic acid or input virus control. The inoculum was incubated for 90 minutes at 36±2°C with 5±3% CO2. The inoculum was removed, and the wells were washed three times with PBS. 1.0 mL of each dose of tranexamic acid (or DM for input virus control) was added to each well. The plates were incubated for 48±8 hours at 36±2°C with 5±3% CO2. The plates were then frozen at -60 to -90°C for 6 days, thawed, and the contents of each well were centrifuged at 2,000 RPM for 10 minutes. The supernatant from each well was collected and assayed for infectious virus.

[0056] The titer results are shown in Table 4 below and are the input virus control titers (Log 10 TCID 50 / mL) ranged from 6.13 ± 0.09 to 6.31 ± 0.08 with a mean of 6.22 ± 0.08, and the virus strain titer control had a titer of 2.68 ± 0.20. 10 TCID 50 Sample amounts of 0.5% (w / v), 1.0% (w / v), and 2.0% tranexamic acid with a % w / v concentration (w / mL) were used in the study. TIFF2025166032000004.tif141170

[0057] Preparations for evaluation of the antiviral activity of tranexamic acid against HSV-2 for high virus inocula were prepared as follows: 0.25 mL of virus inoculum (10 3.8 TCID 50Units) were added to triplicate wells for each dose of tranexamic acid or input virus control. The inoculum was incubated for 90 minutes at 36±2°C with 5±3% CO2. The inoculum was removed, and the wells were washed three times with PBS. 1.0 mL of each dose of tranexamic acid (or DM for input virus control) was added to each well. The plates were incubated for 48±8 hours at 36±2°C with 5±3% CO2. The plates were then frozen at -60 to -90°C for 6 days, thawed, and the contents of each well were centrifuged at 2,000 RPM for 10 minutes. The supernatant from each well was collected and assayed for infectious virus.

[0058] The titer results are shown in Table 5 below and are the input virus control titers (Log 10 TCID 50 The titer values ​​(Log 1 / mL) ranged from 7.74±0.11 to 7.92±0.09 with a mean of 7.83±0.09, and the virus strain titer control had a titer of 4.43±0.18. 10 TCID 50 Sample amounts of 0.5% (W / v), 1.0% (w / v), and 2.0% (w / v) tranexamic acid with a % w / v concentration (w / mL) were used in the study. TIFF2025166032000005.tif140170

[0059] Using the average of the input virus controls as the input virus titer, the resulting reduction factors are shown in Table 6 below. As seen in Table 6, the reduction rates were greatest at low virus inocula of 78.94% for 0.5% (w / v) tranexamic acid, 75.82% for 1.0% (w / v) tranexamic acid, and 98.67% for 2.0% (w / v) tranexamic acid. The data show that at low virus inocula, 2.0% (w / v) tranexamic acid resulted in a higher reduction rate, while at high virus inocula, the reduction rate generally increased as the percentage of tranexamic acid increased. At high virus inocula, the reduction rates were greatest at 52.85% for 0.5% (w / v) tranexamic acid, 64.24% for 1.0% (w / v) tranexamic acid, and 99.98% for 2.0% (w / v) tranexamic acid. Of particular note is the reduction rate of 2.0% (W / v) tranexamic acid, as indicated by both low and high virus inoculations showing a reduction of over 98%. TIFF2025166032000006.tif140170

[0060] Antiviral activity of tranexamic acid against human immunodeficiency virus type 1 (HIV-1) Each sample tested below was replicated three times and consisted of an input virus control of 0% (w / v) tranexamic acid, 2.0% (w / v), 3.0% (w / v), and 4.0% (w / v) tranexamic acid for low and high virus inocula. The contact time for each sample was 48±8 hours, and the input virus titer (Log 10 TCID 50 ) and output virus titer (Log 10 TCID 50 ) to generate the reduction factor, resulting in Log 10 The reduction coefficient and correlation reduction rate were obtained.

[0061] Preparations for evaluation of the antiviral activity of tranexamic acid against HIV-1 for low virus inocula were prepared as follows: 0.5 mL of virus inoculum (10 2.0 TCID 50Units) were added to triplicate wells for each dose of tranexamic acid or input virus control. 1.0 mL of each dose of tranexamic acid (or DM for input virus control) was added to each well. Plates were incubated at 36±2°C in 5±3% CO2 for 48±8 hours. Plates were then frozen at -60 to -90°C for 1 day, thawed, and the contents of each well were centrifuged at 2,000 RPM for 10 minutes. Supernatants were collected from each well and assayed for infectious virus.

[0062] The titer results are shown in Table 7 below, and the low virus inoculum showed a significantly higher input virus control titer (Log 10 TCID 50 / mL) ranged from 4.34±0.10 to 4.46±0.10 with a mean of 4.40±0.08, and the virus strain titer control had a titer of 2.30±0.19. 10 TCID 50 Sample amounts of tranexamic acid of 2.0% (w / v), 3.0% (w / v), and 4.0% (w / v) with a concentration of 1000 mg / mL were used in the study. TIFF2025166032000007.tif135170

[0063] Preparations for evaluation of the antiviral activity of tranexamic acid against HIV-1 for high virus inocula were prepared as follows: 0.5 mL of virus inoculum (10 3.88 TCID 50 Units) were added to triplicate wells for each dose of tranexamic acid or input virus control. 1.0 mL of each dose of tranexamic acid (or DM for input virus control) was added to each well. Plates were incubated at 36±2°C in 5±3% CO2 for 48±8 hours. Plates were then frozen at -60 to -90°C for 1 day, thawed, and the contents of each well were centrifuged at 2,000 RPM for 10 minutes. Supernatants were collected from each well and assayed for infectious virus.

[0064] The titer results are shown in Table 8 below, and the high virus inoculum showed a higher titer than the input virus control titer (Log10 TCID 50 / mL) ranged from 5.71 ± 0.10 to 6.31 ± 0.08 with a mean of 6.06 ± 0.09, and the virus strain titer control had a titer of 4.18 ± 0.18. 10 TCID 50 Sample amounts of tranexamic acid of 2.0% (w / v), 3.0% (w / v), and 4.0% (w / v) with a concentration of 1000 mg / mL were used in the study. TIFF2025166032000008.tif135170

[0065] Using the average of the input virus controls as the input virus titer, the resulting reduction factors are shown in Table 9 below. As seen in Table 9, at low virus inocula, reduction rates were greatest at 56.6% for 2.0% (w / v) tranexamic acid, 66.3% for 3.0% (w / v), and 98.6% for 4.0% (w / v). The data show that at low virus inocula, as expected, reduction rates increased with increasing tranexamic acid percentage, while at high virus inocula, reduction rates increased with increasing tranexamic acid percentage. At high virus inocula, reduction rates were greatest at 41.1% for 2.0% (w / v) tranexamic acid, 55.3% for 3.0% (w / v), and 97.1% for 4.0% (w / v). Of particular note is the reduction rate at 4.0% (w / v) tranexamic acid, as indicated by both low and high virus inoculations, where reductions of over 95% were demonstrated. TIFF2025166032000009.tif134170

[0066] Antiviral activity of tranexamic acid against influenza A virus (H3N2) using embryonated chicken eggs as an infection system Each sample tested below was replicated four times and consisted of an input virus control of 0% (w / v) tranexamic acid, 6% (w / v), 8% (w / v), and 10% (w / v) tranexamic acid for low and high virus inocula. The contact time for each sample was 72±8 hours, and the input virus titer (Log 10 TCID50 ) and output virus titer (Log 10 TCID 50 ) to generate the reduction factor, resulting in Log 10 The reduction coefficient and correlation reduction rate were obtained.

[0067] Preparations for evaluation of the antiviral activity of tranexamic acid against H3N2 for low virus inoculation were prepared as follows: 0.2 mL of tranexamic acid-virus mixture (10 3.0 TCID 50 1000 RPM for 15 minutes. The supernatant was then collected and stored at -60 to -90°C until assayed. The supernatant was then collected and assayed for infectious virus.

[0068] The titer results are shown in Table 10 below, and the low virus inoculum showed a significantly higher input virus control titer (Log 10 TCID 50 The titer values ​​(Log 1 / mL) ranged from 7.00±0.28 to 8.00±0.28 with a mean of 7.64±0.27, and the virus strain titer control had a titer of 3.50±0.00. 10 TCID 50 Sample amounts of 6% (w / v), 8% (w / v), and 10% (w / v) tranexamic acid with a concentration of 0.01% (w / v) / mL were used in the study. TIFF2025166032000010.tif157170

[0069] Preparations for evaluation of the antiviral activity of tranexamic acid against H3N2 for high virus inocula were prepared as follows: 0.2 mL of tranexamic acid-virus mixture (10 5.0 TCID 501000 RPM for 15 minutes. The supernatant was then collected and stored at -60 to -90°C until assayed. The supernatant was then collected and assayed for infectious virus.

[0070] The titer results are shown in Table 11 below, and the high virus inoculum showed a significantly higher input virus control titer (Log 10 TCID 50 / mL) ranged from 6.00±0.28 to 7.00±0.28 with a mean of 6.74±0.28, and the virus strain titer control had a titer of 5.50±0.00. The titer values ​​(Log 10 TCID 50 Sample amounts of 6% (w / v), 8% (w / v), and 10% (w / v) tranexamic acid with a concentration of 0.01% (w / v) / mL were used in the study. TIFF2025166032000011.tif157170

[0071] Using the mean of the input virus controls as the input virus titer, the resulting reduction factors are shown in Table 12 below, where the low virus inoculum is 10 3.0 TCID 50 / mL, and the high virus inoculum is 10 5.0 TCID 50 / mL. As seen in Table 12, the percent reduction was greatest at low virus inocula: 95.96% for 6% (w / v) tranexamic acid, 99.98% for 8% (w / v) tranexamic acid, and 99.99% for 10% (w / v) tranexamic acid. The data show that at low virus inocula, as expected, the percent reduction increases with increasing tranexamic acid percentage; at high virus inocula, the percent reduction increases with increasing tranexamic acid percentage; however, 6% (w / v) tranexamic acid showed no virus reduction in three of four replicates. At high virus inocula, the percent reduction was greatest: 42.50% for 6% (w / v) tranexamic acid, 81.82% for 8% (w / v) tranexamic acid, and 99.82% for 10% (w / v) tranexamic acid. Of particular note is the reduction rate of 10% (w / v) tranexamic acid, as indicated by both low and high virus inoculations showing a reduction of over 99%. TIFF2025166032000012.tif162170

[0072] Antiviral activity of tranexamic acid / L-arginine against herpes simplex virus type 1 (HSV-1) Each sample tested, listed below, was replicated three times and consisted of an input virus control (no excess tranexamic acid or L-arginine), 2% (w / v) tranexamic acid, 5,000 μM L-arginine, 10,000 μM L-arginine, 25,000 μM L-arginine, and a mixture of 2% (w / v) tranexamic acid with 5,000 μM L-arginine, 10,000 μM L-arginine, and 25,000 μM L-arginine. The tranexamic acid and L-arginine mixture was prepared at twice the concentration of each component, and each component was diluted with an equal volume to achieve the final concentrations listed above. The contact time for each sample was 48 ± 8 hours, and the input virus titer (Log 10 TCID 50 ) and output virus titer (Log 10 TCID 50 ) to generate the reduction factor and the corresponding Log 10 Differences in potency were shown, resulting in correlated reduction or enhancement rates.

[0073] Preparations for evaluation of the antiviral activity of tranexamic acid / L-arginine against HSV-1 were prepared as follows: 0.25 mL of virus inoculum (10 3.0 TCID 50 A total of 1.0 mL of 1000 ng / ml of tranexamic acid, L-arginine, a combination of tranexamic acid and L-arginine, or DM (input virus control) was added to three wells for each dose of tranexamic acid, L-arginine, a combination of tranexamic acid and L-arginine, or input virus control. 1.0 mL of each dose of tranexamic acid, L-arginine, a combination of tranexamic acid and L-arginine, or DM (input virus control) was added to each well. The plates were incubated at 5±3% CO2 and 36±2°C for 48±8 hours. The plates were then frozen at -60 to -90°C for 1 day, thawed, and the contents of each well were centrifuged at 2,000 RPM for 10 minutes. The supernatant from each well was collected and assayed for infectious virus.

[0074] The titer results are shown in Table 13 below, and the virus inoculations were compared to the input virus control titer (Log 10 TCID 50 The titer values ​​(Log 1 / mL) ranged from 6.25±0.11 to 6.55±0.12 with a mean of 6.39±0.10, and the virus strain titer control had a titer of 3.68±0.20. 10 TCID 50 Sample amounts of 2% (w / v) tranexamic acid, 5,000 μM L-arginine, 10,000 μM L-arginine, 25,000 μM L-arginine, and mixtures of 2% (w / v) tranexamic acid with 5,000 μM L-arginine, 10,000 μM L-arginine, and 25,000 μM L-arginine were used in the study, each having a concentration of 1000 μM L-arginine / mL. TIFF2025166032000013.tif194170

[0075] Using the average of the input virus controls as the input virus titer, the resulting reduction factors are shown in Table 14 below. As can be seen in Table 14, reduction was greatest at 95% with 2% (w / v) tranexamic acid, while samples containing L-arginine (at 5,000 μM, 10,000 μM, and 25,000 μM) showed no viral reduction but rather viral enhancement. Viral enhancement was greatest at 54% with 5,000 μM L-arginine, 85% with 10,000 μM L-arginine, and 85% with 25,000 μM L-arginine. Samples containing 2% (w / v) tranexamic acid and L-arginine showed contrasting results in viral reduction compared to samples containing only L-arginine. The greatest viral reduction was 88% for the combination of 2% (w / v) tranexamic acid and 5,000 μM L-arginine, 99% for the combination of 2% (w / v) tranexamic acid and 10,000 μM L-arginine, and 99.99% for the combination of 2% (w / v) tranexamic acid and 25,000 μM L-arginine. As demonstrated by the data below, the combination of 2% (w / v) tranexamic acid and 25,000 μM L-arginine showed greater than 99% viral reduction. TIFF2025166032000014.tif161170

[0076] Antiviral activity of tranexamic acid / L-arginine against herpes simplex virus type 2 (HSV-2) Each sample tested, listed below, was replicated three times and consisted of an input virus control (no excess tranexamic acid or L-arginine), 2% (w / v) tranexamic acid, 5,000 μM L-arginine, 10,000 μM L-arginine, 25,000 μM L-arginine, and a mixture of 2% (w / v) tranexamic acid with 5,000 μM L-arginine, 10,000 μM L-arginine, and 25,000 μM L-arginine. The tranexamic acid and L-arginine mixture was prepared at twice the concentration of each component, and each component was diluted with an equal volume to achieve the final concentrations listed above. The contact time for each sample was 48 ± 8 hours, and the input virus titer (Log 10 TCID 50) and output virus titer (Log 10 TCID 50 ) to generate the reduction factor and the corresponding Log 10 Differences in potency were shown, resulting in correlated reduction or enhancement rates.

[0077] Preparations for evaluation of the antiviral activity of tranexamic acid / L-arginine against HSV-2 were prepared as follows: 0.25 mL of virus inoculum (10 3.0 TCID 50 A total of 1.0 mL of 1000 ng / ml of tranexamic acid, L-arginine, a combination of tranexamic acid and L-arginine, or DM (input virus control) was added to three wells for each dose of tranexamic acid, L-arginine, a combination of tranexamic acid and L-arginine, or input virus control. 1.0 mL of each dose of tranexamic acid, L-arginine, a combination of tranexamic acid and L-arginine, or DM (input virus control) was added to each well. The plates were incubated at 5±3% CO2 and 36±2°C for 48±8 hours. The plates were then frozen at -60 to -90°C for 1 day, thawed, and the contents of each well were centrifuged at 2,000 RPM for 10 minutes. The supernatant from each well was collected and assayed for infectious virus.

[0078] The titer results are shown in Table 15 below, and the virus inoculations were compared to the input virus control titer (Log 10 TCID 50 / mL) ranged from 4.82±0.11 to 5.00±0.13 with a mean of 4.93±0.10, and the virus strain titer control had a titer of 3.18±0.18. 10 TCID 50 Sample amounts of 2% (w / v) tranexamic acid, 5,000 μM L-arginine, 10,000 μM L-arginine, 25,000 μM L-arginine, and mixtures of 2% (w / v) tranexamic acid with 5,000 μM L-arginine, 10,000 μM L-arginine, and 25,000 μM L-arginine were used in the study, each having a concentration of 1000 μM L-arginine / mL. TIFF2025166032000015.tif200170

[0079] Using the average of the input virus controls as the input virus titer, the resulting reduction factors are shown in Table 16 below. As can be seen in Table 16, reduction was greatest at 99.7% with 2% (w / v) tranexamic acid, while samples containing L-arginine (5,000 μM, 10,000 μM, and 25,000 μM) mostly showed viral enhancement, with the exception of the 5,000 μM L-arginine sample in replicate 3 and the 25,000 μM L-arginine sample in replicate 2, which showed viral reductions of 32% and 66%, respectively. Viral enhancement was greatest at 76% with 5,000 μM L-arginine, 76% with 10,000 μM L-arginine, and 3% with 25,000 μM L-arginine. Samples containing 2% (w / v) tranexamic acid and L-arginine showed contrasting results in terms of virus reduction compared to samples containing only L-arginine. The greatest virus reduction was achieved with 2% (w / v) tranexamic acid in combination with 5,000 μM L-arginine (99.8%), 2% (w / v) tranexamic acid in combination with 10,000 μM L-arginine (99.9%), and 2% (w / v) tranexamic acid in combination with 25,000 μM L-arginine (99.96%). As demonstrated by the data presented below, combinations of 2% (w / v) tranexamic acid in combination with L-arginine (5,000 μM, 10,000 μM, and 25,000 μM) demonstrated greater than 99% virus reduction. TIFF2025166032000016.tif151170

[0080] Antiviral activity of tranexamic acid against herpes simplex virus type 1 (HSV-1) utilizing arginine and histidine Each sample tested, shown below, was replicated three times and consisted of an input virus control (no excess compound), 2% (w / v) tranexamic acid, 0.5 mM L-arginine, 2 mM L-arginine, 5 mM L-arginine, and a mixture of 2% (w / v) tranexamic acid with 0.5 mM L-arginine, 2 mM L-arginine, and 5 mM L-arginine. The tranexamic acid and L-arginine mixture was prepared at twice the concentration value of each component, and each component was diluted with an equal volume to achieve the final concentrations listed above. The contact time for each sample was 48 ± 2 hours, and the input virus titer (Log 10 TCID 50 ) and output virus titer (Log 10 TCID 50 ) to Log 10 A decrease in titer was produced.

[0081] Preparations for evaluation of the antiviral activity of tranexamic acid / L-arginine against HSV-1 were prepared as follows: 0.25 mL of virus inoculum (10 3.0 TCID 50 Units) were added to three wells for each dose of tranexamic acid, L-arginine, a combination of tranexamic acid and L-arginine, or input virus control. 1.0 mL of each dose of tranexamic acid, L-arginine, a combination of tranexamic acid and L-arginine, or DM (input virus control) was added to each well. Plates were incubated at 36±2°C with 5±3% CO2 for 48±2 hours. Plates were then frozen at -60 to -90°C, thawed, and the contents of each well were centrifuged at 2,000 RPM for 10 minutes. Supernatants from each well were collected and assayed for infectious virus.

[0082] The titer results are shown in Table 17 below, and the virus inoculations were compared to the input virus control titer (Log 10 TCID 50 The titer values ​​(Log 1 / mL) ranged from 8.34±0.10 to 8.64±0.06 with a mean of 8.50±0.09, and the virus strain titer control had a titer of 3.68±0.20. 10TCID 50 Sample amounts of 2% (w / v) tranexamic acid, 0.5 mM L-arginine, 2 mM L-arginine, 5 mM L-arginine, and mixtures of 2% (w / v) tranexamic acid with 0.5 mM L-arginine, 2 mM L-arginine, and 5 mM L-arginine, each having a concentration of 1000 mg / mL, were used in the study. TIFF2025166032000017.tif198170

[0083] Each sample tested below was replicated three times and consisted of 0.5 mM L-histidine, 1 mM L-histidine, 5 mM L-histidine, 10 mM L-histidine, 25 mM L-histidine, and a mixture of 2% (w / v) tranexamic acid with 0.01 mM L-histidine, 0.05 mM L-histidine, 0.1 mM L-histidine, 0.25 mM L-histidine, and 0.5 mM L-histidine, respectively. The tranexamic acid and L-histidine mixtures were prepared at twice the concentration of each component, and each component was diluted with an equal volume to obtain the final concentrations listed above. The contact time for each sample was 48 ± 2 hours, and the input virus titer (Log 10 TCID 50 ) and output virus titer (Log 10 TCID 50 ) to Log 10 A decrease in titer was produced.

[0084] Preparations for evaluation of the antiviral activity of tranexamic acid / L-histidine against HSV-1 were prepared as follows: 0.25 mL of virus inoculum (10 3.0 TCID 50Units) were added to triplicate wells for each dose of L-histidine or the combination of tranexamic acid and L-histidine. 1.0 mL of each dose of L-histidine or tranexamic acid and L-histidine was added to each well. The plates were incubated at 36±2°C in 5±3% CO2 for 48±2 hours. The plates were then frozen at -60 to -90°C, thawed, and the contents of each well were centrifuged at 2,000 RPM for 10 minutes. The supernatant from each well was collected and assayed for infectious virus.

[0085] The titer results are shown in Table 18 below. The following titer values ​​(Log 10 TCID 50 Sample volumes of 0.5 mM L-histidine, 1 mM L-histidine, 5 mM L-histidine, 10 mM L-histidine, 25 mM L-histidine, and mixtures of 2% (w / v) tranexamic acid with 0.01 mM L-histidine, 0.05 mM L-histidine, 0.1 mM L-histidine, 0.25 mM L-histidine, and 0.5 mM L-histidine, with a concentration of 0.5 mM L-histidine / mL, were used in the study. TIFF2025166032000018.tif201170

[0086] Each sample tested below was replicated three times and contained 2% (w / v) tranexamic acid and 0.5 mM L-arginine and 0.5 mM L-histidine, 0.5 mM L-arginine and 5 mM L-histidine, 0.5 mM L-arginine and 10 mM L-histidine, 2 mM L-arginine and 0.05 mM L-histidine, respectively. The mixtures consisted of 2 mM L-histidine, 2 mM L-arginine and 0.5 mM L-histidine, 2 mM L-arginine and 5 mM L-histidine, 5 mM L-arginine and 0.05 mM L-histidine, 5 mM L-arginine and 0.5 mM L-histidine, and 5 mM L-arginine and 5 mM L-histidine. Mixtures of tranexamic acid with L-arginine and L-histidine were prepared at three times the concentration of each component, and each component was diluted with an equal volume to obtain the final concentrations listed above. The contact time for each sample was 48 ± 2 hours, and the input virus titer (Log 10 TCID 50 ) and output virus titer (Log 10 TCID 50 ) to Log 10 A decrease in titer was produced.

[0087] Preparations for evaluation of the antiviral activity of tranexamic acid in combination with L-arginine and L-histidine against HSV-1 were prepared as follows: 0.25 mL of virus inoculum (10 3.0 TCID 50 Units) were added to three wells for each dose of tranexamic acid in combination with L-arginine and L-histidine. 1.0 mL of each dose of tranexamic acid in combination with L-arginine and L-histidine was added to each well. The plates were incubated at 36±2°C in 5±3% CO2 for 48±2 hours. The plates were then frozen at -60 to -90°C, thawed, and the contents of each well were centrifuged at 2,000 RPM for 10 minutes. The supernatant from each well was collected and assayed for infectious virus.

[0088] The titer results are shown in Table 19 below. The following titer values ​​(Log 10 TCID 50Combinations of tranexamic acid at a sample volume of 2% (w / v) with 0.5 mM L-arginine and 0.5 mM L-histidine, 0.5 mM L-arginine and 5 mM L-histidine, 0.5 mM L-arginine and 10 mM L-histidine, 2 mM L-arginine and 0.05 mM L-histidine, 2 mM L-arginine and 0.5 mM L-histidine, 2 mM L-arginine and 5 mM L-histidine, 5 mM L-arginine and 0.05 mM L-histidine, 5 mM L-arginine and 0.5 mM L-histidine, and 5 mM L-arginine and 5 mM L-histidine, each having a 2% (w / v) concentration of tranexamic acid in a 2% (w / v) solution (1000 mg / mL). TIFF2025166032000019.tif221170

[0089] The average of the input virus controls for 2% (w / v) tranexamic acid, 0.5 mM L-arginine, 2 mM L-arginine, 5 mM L-arginine, and mixtures of 2% (w / v) tranexamic acid with 0.5 mM L-arginine, 2 mM L-arginine, and 5 mM L-arginine was used as the input virus titer. The resulting Log 10 The titer reduction is shown in Table 20 below. As shown below, Log 10 The maximum reduction in potency was 1.29 with 2% (w / v) tranexamic acid, 0.28 with 0.5 mM L-arginine, and 0.04 with 2 mM L-arginine, while 5 mM L-arginine was Log 10 No decrease in titer was observed. 10 The greatest reductions in potency were 0.88 for the combination of 2% (w / v) tranexamic acid and 0.5 mM L-arginine, 0.88 for the combination of 2% (w / v) tranexamic acid and 2 mM L-arginine, and 1.47 for the combination of 2% (w / v) tranexamic acid and 5 mM L-arginine. TIFF2025166032000020.tif185170

[0090] The average of the input virus controls for 0.5 mM L-histidine, 1 mM L-histidine, 5 mM L-histidine, and 10 mM L-histidine was used as the input virus titer, and the resulting Log 10 The titer reduction is shown below in Table 21. As shown below, the Log 10 The titer reduction was greatest at 0.04 for 0.5 mM L-histidine and 0.10 for 1 mM L-histidine, while the remaining samples were Log 10 No decrease in titer was observed. TIFF2025166032000021.tif119170

[0091] The average of the input virus controls combining 2% (w / v) tranexamic acid with 0.01 mM L-histidine, 0.05 mM L-histidine, 0.1 mM L-histidine, 0.25 mM L-histidine, and 0.5 mM L-histidine was used as the input virus titer, and the resulting Log 10 The titer reduction is shown in Table 22 below. As shown below, Log 10 The greatest reductions in potency were observed for the combination of 2% (w / v) tranexamic acid and 0.01 mM L-histidine (1.77), 2% (w / v) tranexamic acid and 0.05 mM L-histidine (1.53), 2% (w / v) tranexamic acid and 0.1 mM L-histidine (1.53), 2% (w / v) tranexamic acid and 0.25 mM L-histidine (1.59), and 2% (w / v) tranexamic acid and 0.5 mM L-histidine (1.89). TIFF2025166032000022.tif142170

[0092] The average of the input virus controls combining 2% (w / v) tranexamic acid with 0.5 mM L-arginine and 0.5 mM L-histidine, 0.5 mM L-arginine and 5 mM L-histidine, 0.5 mM L-arginine and 10 mM L-histidine, 2 mM L-arginine and 0.05 mM L-histidine, 2 mM L-arginine and 0.5 mM L-histidine, 2 mM L-arginine and 5 mM L-histidine, 5 mM L-arginine and 0.05 mM L-histidine, 5 mM L-arginine and 0.5 mM L-histidine, and 5 mM L-arginine and 5 mM L-histidine was used as the input virus titer, and the resulting Log 10 The titer reduction is shown in Table 23 below. As shown below, Log 10 The reduction in potency was 0.40 for the combination of 2% (w / v) tranexamic acid with 0.5 mM L-arginine and 0.5 mM L-histidine, 1.00 for the combination of 2% (w / v) tranexamic acid with 0.5 mM L-arginine and 5 mM L-histidine, 2.73 for the combination of 2% (w / v) tranexamic acid with 0.5 mM L-arginine and 10 mM L-histidine, 0.94 for the combination of 2% (w / v) tranexamic acid with 2 mM L-arginine and 0.05 mM L-histidine, and 0.10 for the combination of 2% (w / v) tranexamic acid with 2 mM L-arginine and 0.05 mM L-histidine. The highest values ​​were 1.00 for the combination of 2% (w / v) tranexamic acid with 2 mM L-arginine and 5 mM L-histidine, 1.83 for the combination of 2% (w / v) tranexamic acid with 2 mM L-arginine and 5 mM L-histidine, 0.88 for the combination of 2% (w / v) tranexamic acid with 5 mM L-arginine and 0.05 mM L-histidine, 0.76 for the combination of 2% (w / v) tranexamic acid with 5 mM L-arginine and 0.5 mM L-histidine, and 1.59 for the combination of 2% (w / v) tranexamic acid with 5 mM L-arginine and 5 mM L-histidine. TIFF2025166032000023.tif209170

[0093] Summary of results As previously discussed, various percentages of tranexamic acid have been used to demonstrate the reduction of viral replication of HSV-1, HSV-2, HIV, and H3N2. Generally, 2.0% (w / v) tranexamic acid showed the best results for HSV-1 and HSV-2 at both low and high viral inocula, while HSV-1 showed high reduction rates even at lower tranexamic acid percentages. For HIV, higher percentages of tranexamic acid, such as 4.0% (w / v), showed very good results at both low and high viral inocula. For H3N2, the antiviral efficacy of tranexamic acid was shown to be dose-dependent and related to viral load. For example, 8% (w / v) and 10% (w / v) tranexamic acid were effective at reducing viral replication at low viral loads (10 3.0 TCID 50 / mL), whereas 10% (w / v) tranexamic acid reduced the viral load at high levels (10 5.0 TCID 50 / mL) shows a high reduction rate.

[0094] Furthermore, as shown above, the addition of arginine significantly improves the antiviral efficacy of tranexamic acid against HSV-1 and HSV-2. For HSV-1, the data suggest that a combination of 2% (w / v) tranexamic acid with 10,000 μM L-arginine increases viral reduction to 99%, as opposed to the peak 95% reduction achieved with 2% (w / v) tranexamic acid alone. Furthermore, the data suggest that a combination of 2% (w / v) tranexamic acid with 25,000 μM L-arginine increases viral reduction to 99.99%. For HSV-2, the data suggest that combinations of 2% (w / v) tranexamic acid with 5,000 μM, 10,000 μM, and 25,000 μM L-arginine demonstrate greater than 99% viral reduction.

[0095] To demonstrate the mechanism of action of tranexamic acid in inhibiting HSV-1 and HSV-2 replication by antagonizing arginine, we designed a laboratory study combining tranexamic acid with arginine. We added various amounts of arginine to tranexamic acid-treated cells to determine whether this aided viral replication. Surprisingly, the results suggested that tranexamic acid, at least in combination with higher levels of arginine, inhibited the viruses more than tranexamic acid alone. These results encouraged further investigation.

[0096] Previous studies have shown that histidine is a key amino acid involved in herpes replication, followed by arginine, but subsequent studies have focused on lysine, which competes with arginine, rather than histidine. Lysine, arginine, and histidine are three basic (non-acidic) amino acids whose structures are so similar that some people consider them, especially lysine and arginine, to be analogs of each other.

[0097] Based on the laboratory data presented above, it is believed that an excess of one of the three basic amino acids may antagonize the other two. Furthermore, an excess of two basic amino acids may antagonize the third. Similarly, the same applies to analogs or mimetics such as tranexamic acid instead of lysine. Based on the aforementioned laboratory tests and studies, it is believed that in sufficient amounts, tranexamic acid antagonizes arginine and histidine, while a mixture of tranexamic acid and arginine antagonizes histidine, and a mixture of tranexamic acid and histidine antagonizes arginine. Essentially, the addition of one or more amino acids to tranexamic acid can significantly improve the efficacy of its antiviral activity. This improvement in efficacy is achieved by the presence of an excess of an amino acid that antagonizes another amino acid (e.g., the combination of tranexamic acid and arginine, which acts as lysine, antagonizes histidine).

[0098] Normal physiological concentrations of arginine and histidine within cells are approximately 0.1 to 1 mM, or approximately 0.5 mM on average. Herpes viruses require approximately 0.5 mM of both arginine and 0.5 mM of histidine for efficient replication, and at 0.5 mM each, arginine and histidine do not antagonize each other. However, the above-mentioned studies show that 2% (w / v) tranexamic acid antagonizes both arginine and histidine, reducing the effectively available concentrations of arginine and histidine to significantly below 0.5 mM each. Without being bound by theory, it is believed that arginine may be the primary or most direct target, while histidine may be a secondary or indirect target.

[0099] The above study shows that adding back 0.5 mM arginine helps relieve the "blocking effect" of arginine, but histidine is still not restored, so there is only partial rescue. Adding back 0.5 mM histidine does not help rescue because the direct target, arginine, is still "blocked." However, adding back both 0.5 mM arginine and 0.5 mM histidine relieves the effect of tranexamic acid and almost completely rescues herpes virus replication.

[0100] Based on the above studies, it is possible to provide an indication that both arginine and histidine begin to antagonize each other at concentrations above 10 mM (e.g., in excess of physiological levels). Thus, it is anticipated that a combination of 2% (w / v) tranexamic acid with 10 or 25 mM arginine will exhibit a higher level of viral inhibition than 2% (w / v) tranexamic acid alone. This is because a sample combining 2% (w / v) tranexamic acid with 0.5 mM arginine and 10 mM histidine exhibited a higher level of viral inhibition than 2% (w / v) tranexamic acid alone. It should be noted that the combination of 2% (w / v) tranexamic acid with 10 mM histidine could not be evaluated in the studies conducted due to cytotoxicity. Furthermore, concentrations of 2 to 5 mM arginine or histidine may be close to borderline levels, as they may show some degree of rescue effect beyond 2% (w / v) tranexamic acid.

[0101] It is expected that the antiviral effect of tranexamic acid can be enhanced by combining it with one or more amino acids. Combinations may include, but are not limited to, combinations of tranexamic acid with aliphatic amino acids, aromatic amino acids, acidic amino acids, basic amino acids, neutral amino acids, native amino acids, amino acid analogs or mimetics, or any combination thereof. Furthermore, it is believed that various combinations of tranexamic acid (or other synthetic lysine or mimetics) with amino acids will allow for high-dose compositions without toxicity.

[0102] It should be noted that the percentage of tranexamic acid used in these laboratory studies was limited by the specific cell culture medium used. For example, 2% (w / v) tranexamic acid was the maximum concentration of tranexamic acid that could be used against HSV-1 and HSV-2 without cytotoxicity, and 4% (w / v) tranexamic acid was the maximum concentration that could be used against HIV-1. However, much higher concentrations of synthetic lysine analogs can be used in the human body, which exhibits different biological behavior, e.g., an active metabolism. Typical topical use ranges from 3 to 10% (w / v), and studies have shown that concentrations up to 30% (w / v) can be safely administered. Therefore, the above-mentioned laboratory studies provide strong evidence of the efficacy of tranexamic acid in inhibiting these viruses, and even higher concentrations of synthetic lysine analogs are envisioned for clinical use. Furthermore, as previously demonstrated, the combination of tranexamic acid and arginine may interfere with the activity of histidine by antagonizing it. This may allow for the combination of higher doses of tranexamic acid and arginine without cytotoxicity.

[0103] Therapeutic and prophylactic uses in human subjects In addition to the laboratory tests described above, various therapeutic and prophylactic use studies have been conducted and documented for human subjects. For example, therapeutic activity is demonstrated in a 54-year-old female subject with a history of recurrent outbreaks of herpes labialis on or near the lips. In this case, the subject noticed the first signs of an outbreak—in this case, a red sore surrounded by small white spots, accompanied by tingling, pain, and sensitivity—and immediately applied a small amount of approximately 0.25 mL of a 5% (w / v) aqueous solution of tranexamic acid to the area with a simple swab. This was repeated five times over a 36-hour period. Surprisingly, within 36 hours, the herpes labialis had healed to the point where only a small red dot was visible, and it completely resolved shortly thereafter. This activity represented a significant improvement over the typical duration of the subject's outbreak, which typically lasted approximately 14 days, even with topical antiviral treatments such as ABREVA®. A 5% (w / v) concentration of tranexamic acid has proven effective, but a range of concentrations and total doses, such as 0.5 to 30% (w / v) delivered in 0.25 to 5 mL increments over a period of 1 to 14 days, may prove beneficial as well.

[0104] In addition to the above treatment studies, a further study was conducted in three human subjects experiencing recurrent herpes labialis, which typically lasts approximately two weeks. Upon detecting the onset of an outbreak, 3% (w / v) tranexamic acid was applied topically several times daily; the symptoms of the outbreak resolved within 48 hours. A fourth subject experiencing recurrent herpes labialis, who applied ABREVA® for several days only to avoid a larger-than-usual outbreak, applied 10% (w / v) tranexamic acid topically once upon noticing a very small blister. The next morning, the blister disappeared, and the outbreak ceased. Furthermore, one subject applied 3 or 10% (w / v) tranexamic acid to his face daily for approximately one year, experiencing only one herpes labialis outbreak that year, instead of the usual three to five.

[0105] Furthermore, in three cases, individuals who applied a 3% (w / v) solution of tranexamic acid to the nasal passages and throat every 6 to 8 hours experienced symptoms of a cold or flu infection that resolved within 36 to 48 hours, rather than the usual period of approximately 2 weeks.

[0106] Although various embodiments of the present disclosure are illustrated in the accompanying tables and described in the foregoing detailed description, it will be understood that the present disclosure is not limited to the embodiments disclosed herein, but is capable of many rearrangements, modifications, and substitutions without departing from the spirit of the present disclosure as described herein.

[0107] The term "substantially" is defined as largely, but not necessarily entirely, specified, as understood by one of ordinary skill in the art. In any disclosed embodiment, the terms "substantially," "approximately," "generally," and "about" can be substituted for "within [a percentage]" of what is specified, including 0.1, 1, 5, and 10%.

[0108] The foregoing outlines features of several embodiments so that those skilled in the art may better understand aspects of the present disclosure. Those skilled in the art will recognize that this disclosure may readily serve as a basis for designing or modifying other methods and compositions to carry out the same purposes and / or achieve the same advantages of the embodiments introduced herein. Those skilled in the art will also recognize that such equivalent structures do not depart from the spirit and scope of the present disclosure, and that various changes, substitutions, and modifications can be made thereto without departing from the spirit and scope of the present disclosure. The scope of the present invention is to be determined solely by the language of the appended claims. The term "comprising" in the claims is intended to mean "including at least," such that the list of recited elements in the claim is an open group. The terms "a," "an," and other singular terms are intended to include their plural forms unless specifically excluded.

Claims

Claim 1: A composition for treating an infection in a subject with a transient respiratory virus, comprising: the composition comprises a solution for topical administration and comprises 2% to 30% w / v of at least one of tranexamic acid, epsilon-aminocaproic acid (EACA), and AZD6564; and A composition wherein topical administration of said solution as a spray produces a localized effect in the nasopharyngeal mucosa of said subject.

2. A composition for the treatment of an infectious disease as described in claim 1, wherein the transient respiratory virus is one of a common cold virus and an influenza virus.

3. A composition for treating an infectious disease as described in claim 1, wherein the transient respiratory virus is one of respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, coronavirus, adenovirus, and bocavirus.

4. A composition for the treatment of an infection as described in claim 1, wherein the solution contains tranexamic acid.

5. A composition for treating an infection as described in claim 1, wherein the solution contains 10 w / v% tranexamic acid.

6. A composition for the treatment of an infection as described in claim 1, wherein topical administration of the solution as a spray is performed as the first dose and as the second dose.

7. A composition for treating an infection as described in claim 6, wherein the second dose of the solution contains 10 w / v% tranexamic acid.

8. The composition for treating an infection as described in claim 6, wherein a second dose of the spray can be administered to the subject within 24 hours of the first dose being administered.

9. A composition for the treatment of an infectious disease as described in claim 6, wherein topical administration of the solution as a spray is further performed as a first dose, a second dose, a third dose, and a fourth dose.

10. A composition for the treatment of an infection as described in claim 9, wherein the second dose of the solution contains 10 w / v% tranexamic acid.

11. The composition for treating an infection as described in claim 9, wherein the second dose of the spray and the third dose of the spray can be given within 24 hours of the first dose being given.

12. A composition for treating an infectious disease as described in claim 1, wherein the spray has a volume ranging from about 0.25 mL to about 5 mL.

13. The composition for treating an infectious disease described in claim 1, wherein the solution further contains 5 mM to 25 mM of an amino acid selected from arginine, lysine, and histidine.

14. A composition for the treatment of an infection as described in claim 1, wherein topical administration of the spray is performed at the first sign of infection.

15. A composition for the treatment of an infection as described in claim 1, wherein the topical administration of the spray is performed prophylactically, before the first sign of infection.