Antiviral formulations

Abstract

The present disclosure relates to formulations comprising catmint oil, a proteolytic enzyme, an antioxidant, a surfactant; and a solvent, as well as to pharmaceutical compositions comprising the formulations, methods and uses of the formulations to treat or prevent respiratory infections and methods of reducing infectivity of a virus using the formulations.

Description

ANTIVIRAL FORMULATIONSRELATED APPLICATIONS

[0001] The present application claims priority from Australian Provisional Patent Application No. 2024901317, the entire contents of which have been incorporated herein by reference.FIELD

[0002] The present invention relates, inter alia, to the field of antiviral formulations and uses of antiviral formulations. However, it will be appreciated that the invention is not limited to this particular field of use.BACKGROUND

[0003] The following discussion of the prior art is provided to place the invention in an appropriate technical context and enable the advantages of it to be more fully understood. It should be appreciated, however, that any discussion of the prior art throughout the specification should not be considered as an express or implied admission that such prior art is widely known or forms part of the common general knowledge in the field.

[0004] Influenza viruses (Orthomyxoviridae) and coronaviruses are etiological agents causing highly contagious acute respiratory syndromes in humans and animals, posing significant public health problems worldwide. Both viruses can spread from person to person or animal to animal through airborne droplets and aerosols and can also be transmitted through contact with contaminated surfaces. Their spread can be controlled by disinfecting objects and cleaning and sanitising indoor air, as well as vaccination, which can also reduce the spread via aerosols. However, as influenza and coronavirus continually mutate, the available vaccines may not be appropriate to control all the varieties that may be circulating.

[0005] Coronaviruses have been responsible for pandemics, such as the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). Besides SARS-CoV-2, other beta coronaviruses such as SARS-CoV and MERS-CoV have been linked to severe acute respiratory syndrome in humans. A mouse beta coronavirus known as murine hepatitis virus (MHV-1) is commonly used as a substitute for human coronaviruses. The Therapeutic Goods Administration (TGA) of Australia recommends MHV-1 as a surrogate for COVID-19. Phylogenetic studies have shown that SARS-CoV and SARS-CoV-2 belong to beta coronavirus lineage b, MERS-CoV to lineage c, and MHV-1 to lineage a. This categorisation makes MHV-1 more closely related to the SARS-associated coronaviruses compared to other surrogateslike human coronavirus 229E, feline coronavirus, or transmissible gastroenteritis virus, which are alpha coronaviruses from different lineages. Influenza viruses are primarily classified into four types: A, B, C, and D. Of these, types A and B cause most seasonal flu infections in humans. Influenza A viruses are further categorised based on two surface proteins, hemagglutinin (H) and neuraminidase (N), with subtypes like H1 N1 and H3N2 causing significant illness in humans. Pandemics arise when a novel influenza A virus emerges, infects humans, and spreads widely due to little or no pre-existing immunity in the population. Notable influenza pandemics include the 1918 Spanish flu (H1 N1), the 1957 Asian flu (H2N2), the 1968 Hong Kong flu (H3N2), and the 2009 H1 N1 pandemic, each causing widespread illness and mortality. Currently, there are limited strategies for controlling coronaviruses or influenza viruses in aerosolised form.

[0006] A wide variety of Essential oils (EOs) are known the art, each of which have a unique and complex composition of various different chemical compounds, present at a wide range of relative concentrations. Essential oils often contain complex mixtures of volatile organic compounds, such as monoterpenes, sesquiterpenes and phenylpropenes, leading to a diverse spectrum of biological activities that can be difficult to predict. Use of essential oils in pharmaceutical applications is frequently complicated by their highly variable composition, poor standardisation and unpredictable therapeutic effects. Furthermore, essential oils also generally have poor solubility and stability, which introduce challenges in preparing stable formulations.

[0007] It is an object of the present invention to overcome or ameliorate one or more the disadvantages of the prior art, or at least to provide a useful alternative.SUMMARY

[0008] According to a first aspect, the present invention provides a formulation comprising: catmint oil; a proteolytic enzyme; an antioxidant; a surfactant; and a solvent.

[0009] In some embodiments, the catmint oil is derived from a plant of the Nepeta genus, preferably Nepeta nuda or Nepeta cataria, and is selected from the group consisting of: hydrogenated catmint oil (HCO) and non-hydrogenated catmint oil (NHCO) or a mixture thereof.

[0010] In some embodiments, the catmint oil comprises one or more of the following: a-pinene, P-pinene, p-cymene, limonene, 1 ,8-cineole, (E)- -ocimene, trans-pinocarveol, lavandulol,4aa,7a,7aa-nepetalactone, 4aa,7a,7ap-nepetalactone, 4aa,7p,7aa-nepetalactone, (E)- caryophyllene, (E,Z)-iridolactone, a-humelene, dehydronepetalactone and coryophyllene oxide.

[0011] In some embodiments, the catmint oil is present in an amount from about 0.025 wt% to about 0.075 wt%.

[0012] In some embodiments, the antioxidant is present in an amount from about 0.0010 wt% to about 0.005 wt%.

[0013] In some embodiments, the surfactant is present in an amount from about 0.05 wt% to about 0.15 wt%.

[0014] In some embodiments, the proteolytic enzyme is selected from the group consisting of bromelain, papain, trypsin and chymotrypsin.

[0015] In some embodiments, the antioxidant is N-acetylcysteine.

[0016] In some embodiments, the surfactant is a nonionic surfactant.

[0017] In some embodiments, the surfactant is selected from the group consisting of: polysorbate 20 and polysorbate 80.

[0018] In some embodiments, the proteolytic enzyme is present in an amount from about 0.025 wt% to about 0.075 wt%.

[0019] In some embodiments, the solvent is water.

[0020] In a second aspect, the present invention provides a formulation comprising: catmint oil; an antioxidant; a surfactant; and a solvent.

[0021] According to a third aspect, the present invention provides a formulation comprising: hydrogenated catmint (HCO) or non-hydrogenated (NHCO) catmint oil; bromelain;N-acetylcysteine; and polysorbate 20.

[0022] According to a fourth aspect, the present invention provides a formulation comprising:hydrogenated catmint (HCO) (about 0.05 wt%); bromelain (about 0.05 wt%),N-acetylcysteine (about 0.0025 wt%), polysorbate 20 (about 0.1 wt%), and water.

[0023] According to a fifth aspect, the present invention provides a formulation comprising: non-hydrogenated (NHCO) catmint oil (about 0.05 wt%), bromelain (about 0.05 wt%),N-acetylcysteine (about 0.0025 wt%), polysorbate 20 (about 0.1 wt%), and water.

[0024] According to a sixth aspect, the present invention provides a formulation comprising:HCO (about 0.05 wt%),N-acetylcysteine (about 0.0025 wt%), polysorbate 20 (about 0.1 wt%), and water.

[0025] According to a seventh aspect, the present invention provides a pharmaceutical composition comprising the formulation of any one of the preceding aspects.

[0026] According to an eighth aspect, the present invention provides an aerosol comprising the formulation according to any one of the first through sixth aspects.

[0027] According to a ninth aspect, the present invention provides the use of a formulation according to any one of the first through sixth aspects in the manufacture of a medicament for treating or preventing respiratory infection.

[0028] According to a tenth aspect, the present invention provides a method of treating or preventing respiratory infection, the method comprising the step of administering to a patient in need thereof a formulation according to any one of the first through sixth aspects or the pharmaceutical composition of the seventh aspect.

[0029] In some embodiments of the ninth or tenth aspect, the medicament is in aerosolised form.

[0030] In some embodiments, of the eighth or tenth aspect, the aerosol is formed as an ultrasonically generated vapour.

[0031] According to an eleventh aspect, the present invention provides a method of reducing the infectivity of a virus, the method comprising the step of contacting the virus with a formulation according to any one of the first through sixth aspects or the pharmaceutical composition of seventh aspect, wherein the virus is an influenza virus or a coronavirus.

[0032] In some embodiments of the eleventh aspect, contacting the virus comprises the steps of: a) forming an aerosol comprising the formulation according to any one of first to fifth aspects, and b) delivering the aerosol to a target area comprising the virus.

[0033] In some embodiments of the eleventh aspect, in step b) the aerosol is delivered via a ‘stand-alone’ ultrasonic generator, or an ultrasonic generator which is integrated with existing air- conditioning or humidifying systems.

[0034] In some embodiments of the eleventh aspect, the method comprises the step of adding drops, tablets or capsules comprising the formulation to a water reservoir.

[0035] In one embodiment, there is provided a formulation comprising: catmint oil; an additional antiviral agent an antioxidant; a surfactant; and a solvent.

[0036] In another embodiment, there is provided a formulation comprising: catmint oil; bromelain; an antioxidant; a surfactant; and a solvent.Catmint oil

[0037] As used herein “catmint oil” (CO) refers to essential oil derived from a plant of the Nepeta genus (preferably Nepeta nuda or Nepeta cataria), commonly known as “cat mint” or “catnip”. As used herein, the term “essential oil” (EO) refers to a concentrated oil containing volatile compounds. Essential oils (such as catmint oil) may be obtained in any known way. For example,by distillation, steam distillation, solvent extraction, absolute oil extraction, supercritical fluid extraction, or cold pressing of the plant material for which an essential oil is desired. In some embodiments, the catmint oil is produced using steam distillation. The catmint oil can be derived from any part of the Nepeta plant, for example, the leaves, flowers, stem or roots, or a combination thereof. In some embodiments, the catmint oil is derived primarily from the leaves of the Nepeta plant. In some embodiments, the catmint oil is derived primarily from the flowers of the Nepeta plant.

[0038] Catmint oil may be derived from any suitable plant of the Nepeta genus, for example Nepeta faassenii (dropmore), Nepeta faassenii (gletschereis), Nepeta racemosa (snowflake), Nepeta sibirica, Nepeta cataria, Nepeta cataria (citridora), Nepeta pratti, Nepeta subsessilis (sweet dreams), Nepeta grandiflora (dawn to dusk) and Nepeta nuda. In some embodiments, the plant of the Nepeta genus is selected from the group consisting of: Nepeta nuda and Nepeta cataria. In some embodiments, the plant of the Nepeta genus is Nepeta nuda. In some embodiments, the plant of the Nepeta genus is Nepeta cataria.

[0039] In some embodiments, the catmint oil may be modified, derivatised or refined after extraction from the Nepeta plant to provide a modified catmint oil, for example, the catmint oil may be hydrogenated. In some embodiments, the catmint oil is hydrogenated catmint oil (HCO). In some embodiments, the catmint oil has not been hydrogenated (i.e. is non-hydrogenated catmint oil (NHCO)). In some embodiments, the catmint oil is a mixture of hydrogenated catmint oil (HCO) non-hydrogenated catmint oil (NHCO).

[0040] It will be appreciated that the catmint oil may comprise a range of active components, based on the part of the plant and extraction method employed. In some embodiments the catmint oil comprises oxygenated aliphatics in an amount from about 1 to about 4 mol%, or about 2 to about 2.5 mol%. In some embodiments the catmint oil comprises monoterpene hydrocarbons in an amount from about 0.5 to about 3 mol%, or about 1.5 to about 2 mol%. In some embodiments the catmint oil comprises oxygenated monoterpenes in an amount from about 70 to about 90 mol%, or about 80 to about 90 mol%, or about 83 to about 87 mol%. In some embodiments the catmint oil comprises sesquiterpene hydrocarbons in an amount from about 2 to about 6 mol%, or about 3 to about 4 mol%. In some embodiments the catmint oil comprises oxygenated sesquiterpenes in an amount from about 0.5 to about 3 mol%, or about 1 to about 2 mol%. In some embodiments the catmint oil comprises phenylpropane hydrocarbons in an amount from about 0.01 to about 0.07 mol%, or about 0.03 to about 0.05 mol%. In some embodiments the catmint oil comprises oxygenated phenylpropanes in an amount from about 3 to about 10 mol%, or about 5 to about 7 mol%. In some embodiments, the catmint oil comprises one or more oxygenated aliphaticsmonoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons, oxygenated sesquiterpenes, phenylpropane hydrocarbons, or oxygenated phenylpropanes.

[0041] In some embodiments, the catmint oil comprises one or more of the following: nepetalactone, geraniol, a-pinene, sabinene, p-pinene, 1-cyclohexen-1-yl-methyl ketone, triplal, thymol, nepetalactone caryophyllene, a-humulene, dodecenol, spathulenol, dimethyl-2- undecane, 1-octen-3-one, 3-octanone, myrcene, 2-octanol, p-cymene, limonene, eucalyptol (1 ,8- cineole), (Z)- -ocimene, (E)- -ocimene, bergamal, y-terpinene, (Z)-sabinene hydrate, p-linalool, (Z)-rose oxide, (E)-rose oxide, allo-ocimene, (E)-verbenol, isopulegol, p-citronellal, 3-(Z)-nonen-1- ol, 2-(E)-nonen-1-al, (Z)-isocitral, a-terpineol, myrtenol, p-citronellol, nerol, neral, geranial, carvacrol, citronellic acid, citronellyl acetate, neryl acetate, 4a-a,7a,7a- -nepetalactone, p- bourbonene, p-elemene, 4a-a,7p,7a-a-nepetalactone, p-caryophyllene, p-copaene, (Z)-p- farnesene, a-caryophyllene, germacrene D, bicyclogermacrene, p-bisabolene, v-cadinene, p- sesquiphellandrene, caryophyllene oxide, viridiflorol. In some embodiments, the catmint oil comprises one or more of the following: nepetalactone, geraniol, a-pinene, sabinene, p-pinene, 1- cyclohexen-1-yl-methyl ketone, triplal, thymol, nepetalactone caryophyllene, a-humulene, dodecenol, spathulenol, and dimethyl-2-undecane, quercitrin quercetin-3-O-glucoside, and quercetin-3-O-rutinoside. In some embodiments, the catmint oil comprises at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve of the following: nepetalactone, geraniol, a- pinene, sabinene, p-pinene, 1-cyclohexen-1-yl-methyl ketone, triplal, thymol, nepetalactone caryophyllene, a-humulene, dodecenol, spathulenol, and dimethyl-2-undecane.

[0042] In some embodiments, the catmint oil comprises one or more of: a-pinene, p-pinene, p- cymene, limonene, 1 ,8-cineole, (E)-p-ocimene, trans-pinocarveol, lavandulol, 4aa,7a,7aa- nepetalactone, 4aa,7a,7ap-nepetalactone, 4aa,7p,7aa-nepetalactone, (E)-caryophyllene, (E,Z)- iridolactone, a-humelene, dehydronepetalactone and coryophyllene oxide. In some embodiments, the catmint oil comprises at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or sixteen of the following: a-pinene, p-pinene, p-cymene, limonene, 1 , 8 cineole, (E)-p-ocimene, trans-pinocarveol, lavandulol, 4aa,7a,7aa-nepetalactone, 4aa,7a,7ap-nepetalactone, 4aa,7p,7aa-nepetalactone, (E)-caryophyllene, (E,Z)-iridolactone, a- humelene, dehydronepetalactone and coryophyllene oxide. In some embodiments, the amount of a-pinene is from 0.01 to 0.2 mol%, 0.05 to 0.15 mol%, or about 0.1 mol%. In some embodiments, the amount of p-pinene is from 0.01 to 0.2 mol%, 0.05 to 0.15 mol%, or about 0.1 mol%. In some embodiments, the amount of p-cymene is from 0.01 to 0.2 mol%, 0.05 to 0.15 mol%, or about 0.1 mol%. In some embodiments, the amount of limonene is from 0.001 to 0.1 mol%, 0.05 to 0.1 mol%, or less than 0.1 mol%. In some embodiments, the amount of 1 ,8-cineole is from 0.01 to 0.2 mol%, 0.05 to 0.15 mol%, or about 0.1 mol%. In some embodiments, the amount of (E)-p-ocimene is from 0.001 to 0.1 mol%, 0.05 to 0.1 mol%, or less than 0.1 mol%. In some embodiments, the amount oftrans-pinocarveol is from 0.001 to 0.1 mol%, 0.05 to 0.1 mol%, or less than 0.1 mol%. In some embodiments, the amount of lavandulol is from 0.01 to 0.2 mol%, 0.05 to 0.15 mol%, or about 0.1 mol%. In some embodiments, the amount of 4aa,7a,7aa-nepetalactone is from 60 to 95 mol%, 70 to 95 mol%, 75 to 90 mol%, 80 to 90 mol%,80 to 85 mol%, 82 to 87 mol%, or about 80, 81 , 82, 83, 84, 85, 86, 87, 88 or 89 mol%. In some embodiments, the amount of 4aa,7a,7ap-nepetalactone is from 0.5 to 2 mol%, 0.75 to 1.25 mol%, or about 1 mol%. In some embodiments, the amount of 4aa,7p,7aa-nepetalactone is from 0.5 to 3 mol%, 1 to 2 mol%, 1.4 to 1.8 mol% or about 1.6 mol%. In some embodiments, the amount of (E)-caryophyllene is from 0.1 to 1 mol%, 0.4 to 0.8 mol%, or about 0.6 mol%. In some embodiments, the amount of (E,Z)-iridolactone is from 0.01 to 0.2 mol%, 0.05 to 0.15 mol%, or about 0.1 mol%. In some embodiments, the amount of a-humelene is from 0.001 to 0.1 mol%, 0.05 to 0.1 mol%, or less than 0.1 mol%. In some embodiments, the amount of dehydronepetalactone is from 0.01 to 0.2 mol%, 0.05 to 0.15 mol%, or about 0.1 mol%. In some embodiments, the amount of coryophyllene oxide is from 1 to 3 mol%, 1.5 to 2 mol%, or about 1.7 mol%.

[0043] In some embodiments, the catmint oil comprises flavonol quercetin, quercitrin, quercetin-3-O-glucoside, and quercetin-3-O-rutinoside. In some embodiments, the amount of flavonol quercetin is from about 80 to about 100 mg / g, from about 85 to about 90 mg / g, about 89 mg / g or about 88.97 mg / g. In some embodiments, the amount of quercetin is from about 8000 to about 9000 mg / g, about 8300 to about 8500 mg / g, about 8400 mg / g or about 8406.31 mg / g. In some embodiments, the amount of quercetin-3-O-glucoside is from about 65 to about 85 mg / g, from about 70 to about 75 mg / g, about 73 mg / g or about 72.97 mg / g. In some embodiments, the amount of quercetin-3-O-rutinoside is from about 80 to about 100 mg / g, from about 87 to about 92 mg / g, about 89 mg / g or 86.55 mg / g.

[0044] In formulations of the present invention, the catmint oil may be present in any suitable amount. In some embodiments, the catmint oil is present in an amount from about 0.001 wt% to about 0.5 wt%, about 0.001 wt% to about 0.4 wt%, about 0.001 wt% to about 0.3 wt%, about 0.001 wt% to about 0.2 wt%, about 0.01 wt% to about 0.15 wt%, about 0.0125 wt% to about 0.15 wt%, about 0.01 wt% to about 0.14 wt%, about 0.01 wt% to about 0.13 wt%, about 0.01 wt% to about 0.12 wt%, about 0.01 wt% to about 0.11 wt%, about 0.01 wt% to about 0.10 wt%, about 0.02 wt% to about 0.09 wt%, about 0.03 wt% to about 0.08 wt%, about 0.04 wt% to about 0.07 wt%, about 0.025 wt% to about 0.075 wt%, or about 0.04 wt% to about 0.06 wt%, or any range therein. In some embodiments, the catmint oil is present in an amount of at least 0.01 , 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095, 0.100, 0.105, 0.110, 0.115, 0.120, 0.125, 0.130, 0.135, 0.140 or 0.145 wt%, or any amount in between. In some embodiments, the catmint oil is present in an amount of less than 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095 0.100, 0.105, 0.110,0.115, 0.120, 0.125, 0.130, 0.135, 0.140 or 0.145 or 0.15 wt%, or any amount in between. In some embodiments, the catmint oil is present in an amount of about 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095, 0.100, 0.105, 0.110, 0.115, 0.120, 0.125, 0.130, 0.135, 0.140 or 0.145 or 0.15 wt%, or any amount in between. In some embodiments, the catmint oil is present in an amount from about 0.0125 wt% to about 0.15 wt%. In some embodiments, the catmint oil is present in an amount from about 0.025 wt% to about 0.075 wt%. In some embodiments, the catmint oil is present in an amount of about 0.05 wt%.Antioxidants

[0045] As used herein, the term “antioxidant” refers to compounds which are able to prevent or inhibit oxidation of other molecules, or which are able to act as a reducing agent. Suitable antioxidants may be used alone or in combination as a mixture of two, three, four, five or more antioxidants. It will be appreciated that the antioxidant may also possess antiviral activity. In some embodiments, the antioxidant causes destabilisation of viruses by reducing the disulfide bonds in spike and envelope proteins. In some embodiments the antioxidant is selected from the group consisting of: N-acetylcysteine, L-cysteine, glutathione, alpha-lipoic acid, ascorbic acid, quercetin, resveratrol or N-acetylcysteine amide. In some embodiments the antioxidant is N-acetylcysteine (NAC).

[0046] In formulations of the present invention, the antioxidant may be present in any suitable amount. In some embodiments, the antioxidant is present in an amount from about 0.001 wt% to about 0.5 wt%, about 0.001 wt% to about 0.4 wt%, about 0.001 wt% to about 0.3 wt%, about 0.001 wt% to about 0.2 wt%, about 0.001 wt% to about 0.1 wt%, about 0.001 wt% to about 0.01 wt%, about 0.001 wt% to about 0.005 wt%, about 0.0015 wt% to about 0.0045 wt%, about 0.002 wt% to about 0.004 wt%, about 0.002 wt% to about 0.003 wt%, or any range therein. In some embodiments, antioxidant is present in an amount of at least 0.001 , 0.0015, 0.002, 0.0025, 0.003, 0.0035, 0.004, or 0.0045 wt%, or any amount in between. In some embodiments, the antioxidant is present in an amount of less than 0.0015, 0.002, 0.0025, 0.003, 0.0035, 0.004, 0.0045 or 0.005 wt%, or any amount in between. In some embodiments, the antioxidant is present in an amount of about 0.001 , 0.0015, 0.002, 0.0025, 0.003, 0.0035, 0.004, 0.0045, 0.005 wt%, or any amount in between. In some embodiments, the antioxidant is present in an amount from about 0.0010 wt% to about 0.005 wt%. In some embodiments, the antioxidant is present in an amount of about 0.0025 wt%.

[0047] In some embodiments, the ratio of antioxidant to catmint oil by weight may be from about 1 :1 to about 1 :30, or from about 1 :5 to about 1 :25, or from about 1 :10 to about 1 :25, or from about 1 :15 to about 1 :25, or any range in between. In some embodiments, the ratio of antioxidant to catmint oil by weight is about 1 :1 , 1 :2, 1 :3, 1 :4, 1 :5, 1 :6, 1 :7, 1 :8, 1 :9, 1 :10, 1 :11 , 1 :12, 1 :13, 1 :14,1 :15, 1 :16, 1 :17, 1 :18, 1 :19, 1 :20, 1 :21 , 1 :22, 1 :23, 1 :24, 1 :25, 1 :26, 1 :27, 1 :28, 1 :29, 1 :30, or any range therein. In some embodiment, the ratio of surfactant to catmint oil by weight is from about 1 :15 to about 1 :25. In some embodiment, the ratio of surfactant to catmint oil by weight is 1 :20.Surfactants

[0048] As used herein, the term “surfactant” or surface-active agent refers to an agent, usually an organic chemical compound, that is at least partially amphiphilic (i.e., typically containing a hydrophobic tail group and hydrophilic polar head group). Given their structure, surfactants are generally capable of lowering the surface tension (or interfacial tension) between two liquids or between a liquid and a solid. Further to this, these properties typically allow solubility of the surfactant in organic solvents as well as in water, and allow the surfactant to promote solubilization or at least dispersal of fatty / waxy materials in water and water-containing solutions. In this regard, a surfactant may act as a detergent, a wetting agent, an emulsifying agent, a foaming agent and / or a dispersing agent. Accordingly, in some embodiments, the surfactant is or comprises an emulsifying agent. As generally used herein, the term “emulsifying agent” or “emulsifier” refers to a chemical agent, compound, or substance capable of producing an emulsion by reducing the interfacial tension between the two insoluble liquids. It will be appreciated that in some embodiments, the surfactant may also possess antiviral activity. In some embodiments, the surfactant is capable of solubilising viral lipid envelopes.

[0049] It will be appreciated that a surfactant can have an overall positive charge (i.e. an ionic surfactant), an overall negative charge (i.e. an anionic surfactant) or an overall neutral charge (ie. a non-ionic surfactant or a zwitterionic surfactant). In some embodiments, the surfactant is a nonionic surfactant. As used herein, the term “non-ionic surfactant” refers to a surfactant that does not contain or comprise an ionic or ionizable group. Suitable surfactants may be used alone or in combination as a mixture of two, three, four, five or more surfactants. In some embodiments, the surfactant is selected from the group consisting of: polysorbate 20 (Tween 20), polysorbate 40 (Tween 40), polysorbate 60 (Tween 60), polysorbate 80 (Tween 80), sorbitan monolaurate (Span 20), sorbitan monostearate (Span 60), sorbitan monooleate (Span 80) and sorbitan trioleate (Span 85).

[0050] In formulations of the present invention, the surfactant may be present in any suitable amount. In some embodiments, the surfactant is present in an amount from about 0.001 wt% to about 0.5 wt%, about 0.001 wt% to about 0.4 wt%, about 0.001 wt% to about 0.3 wt%, about 0.001 wt% to about 0.2 wt%, about 0.05 wt% to about 0.15 wt%, about 0.06 wt% to about 0.14 wt%, about 0.07 wt% to about 0.13 wt%, about 0.08 wt% to about 0.12 wt%, about 0.09 wt% to about 0.11 wt%, about 0.095 wt% to about 0.105 wt%, or any range therein. In some embodiments, surfactant is present in an amount of at least 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085,0.09, 0.095, 0.1, 0.105, 0.11, 0.115, 0.12, 0.125, 0.13, 0.135, 0.14, or 0.145 wt%, or any amount in between. In some embodiments, the surfactant is present in an amount of less 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095, 0.1, 0.105, 0.11, 0.115, 0.12, 0.125, 0.13, 0.135, 0.14, 0.145, 0.15 wt%, or any amount in between. In some embodiments, the surfactant is present in an amount of about 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095, 0.1, 0.105, 0.11, 0.115, 0.12, 0.125, 0.13, 0.135, 0.14, 0.145, 0.15 wt%, or any amount in between, in some embodiments, the surfactant is present in an amount from about 0.05 wt% to about 0.15 wt%. In some embodiments, the surfactant is present in an amount from about 0.09 wt% to about 0.11 wt%. In some embodiments, the surfactant is present in an amount of about 0.1 wt%.

[0051] In some embodiments, the ratio of surfactant to catmint oil by weight may from about 20: 1 to about 1 :20, or from about 10:1 to about 1 : 10, or from about 15:1 to about 1 : 1 , or from about 5:1 to about 1:15, or from about 5:1 to about 1:5, or from about 3:1 to about 1:1, or any range therein. In some embodiments, the ratio of surfactant to catmint oil by weight may be about 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1,9:1,8:1,7:1,6:1,5:1,4:1,3:1,2.9:1,2.8:1, 2.7:1, 2.6:1, 2.5:1, 2.4:1, 2.3:1, 2.2:1, 2.1:1, 2:1, 1.9:1, 1.8:1, 1.7:1, 1.6:1, 1.5:1, 1.4:1, 1.3:1, 1.2:1, 1.1:1, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4:, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or any range therein. In some embodiment, the ratio of surfactant to catmint oil by weight is from about 3:1 to about 1:1. In some embodiment, the ratio of surfactant to catmint oil by weight is 2: 1.Solvents

[0052] The term “solvent” refers to any liquid capable of maintaining another substance in solution. Examples of solvents include, but are not limited to, organic solvents and aqueous solvents. It will be apparent to the skilled artisan that the solvent may include any appropriate solvent as are known in the art. Suitable solvents may be used alone or in combination as a mixture of two, three, four, five or more solvents. By way of example, the solvent may be selected from the group consisting of: water, hydrosols, saline, polyethylene glycols, ethanol, acetone, or propylene glycol. In some embodiments, the solvent is an aqueous solvent. In some embodiments, the solvent is water.

[0053] In formulations of the present invention, the solvent (including a combination of solvents) may be present in any suitable amount. In some embodiments, the solvent is present in an amount from about 96 wt% to about 99.9 wt%, about 97 wt% to about 99.9 wt%, about 98 wt% to about 99.9 wt%, about 98.5 wt% to about 99.9 wt%, about 99 wt% to about 99.9 wt%, about 99.5 wt% to about 99.9 wt%, or any range therein. In some embodiments, solvent is present in an amount of at least 96.0, 96.1, 96.3, 96.5, 96.7, 96.9, 97.1, 97.3, 97.5, 97.7, 97.9, 98.1, 98.2, 98.3, 98.4, 98.5,98.6, 98.7, 98.9, 99.0, 99.1 , 99.2, 99.3, 99.4, 99.5, 99.6, 99.7, 99.8, or 99.85 wt%, or any amount in between. In some embodiments, the solvent is present in an amount of less 96.1 , 96.3, 96.5,96.7, 96.9, 97.1 , 97.3, 97.5, 97.7, 97.9, 98.1 , 98.2, 98.3, 98.4, 98.5, 98.6, 98.7, 98.9, 99.0, 99.1 ,99.2, 99.3, 99.4, 99.5, 99.6, 99.7, 99.8, 99.85, or 99.9 wt%, or any amount in between. In some embodiments, the solvent is present in an amount of about 96.0, 96.1 , 96.3, 96.5, 96.7, 96.9, 97.1 ,97.3, 97.5, 97.7, 97.9, 98.1 , 98.2, 98.3, 98.4, 98.5, 98.6, 98.7, 98.9, 99.0, 99.1 , 99.2, 99.3, 99.4, 99.5, 99.6, 99.7, 99.8, 99.85, 99. or 99.9 wt%, or any amount in between. In some embodiments, the solvent is present in an amount from about 99.5 wt% to about 99.9 wt%. In some embodiments the solvent is present in an amount of about 99.8 wt%. In some embodiments the solvent is present in an amount of about 99.85 wt%.Additional antiviral agent

[0054] In some embodiments, the formulation further comprises an additional antiviral agent. Suitable additional antiviral agents may be used alone or in combination as a mixture of two, three, four, five or more additional antiviral agents. In some embodiments, the additional antiviral agent is selected from the group consisting of: proteolytic enzymes (such as bromelain, papain, trypsin and chymotrypsin), sulfinates (such as allicin) and polyphenols (such as curcumin. In some embodiments, the additional antiviral agent is a proteolytic enzyme. As used herein, the term “proteolytic enzyme” (also known as a protease or peptidase) refers to enzymes that break down proteins into smaller peptides or amino acids by cleaving the peptide bonds. In some embodiments, the proteolytic enzyme is selected from the group consisting of: bromelain, papain, trypsin and chymotrypsin. In some embodiments, the proteolytic enzyme is bromelain.

[0055] In formulations of the present invention, the additional antiviral agent may be present in any suitable amount. In some embodiments, the additional antiviral agent is present in an amount from about 0.001 wt% to about 0.5 wt%, about 0.001 wt% to about 0.4 wt%, about 0.001 wt% to about 0.3 wt%, about 0.001 wt% to about 0.2 wt%, about 0.01 wt% to about 0.1 wt%, about 0.02 wt% to about 0.09 wt%, about 0.03 wt% to about 0.08 wt%, about 0.04 wt% to about 0.07 wt%, about 0.025 wt% to about 0.075 wt%, or about 0.04 wt% to about 0.06 wt%, or any range therein. In some embodiments, additional antiviral agent is present in an amount of at least 0.01 , 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09 or 0.095 wt%, or any amount in between. In some embodiments, the additional antiviral agent is present in an amount of less than 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095 or 0.1 wt%, or any amount in between. In some embodiments, the additional antiviral agent is present in an amount of about 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095 or 0.1 wt%, or any amount in between. In some embodiments, the additional antiviral agent is present in anamount from about 0.025 wt% to about 0.075 wt%. In some embodiments, the additional antiviral agent is present in an amount of about 0.05 wt%.

[0056] In some embodiments, the ratio of additional antiviral agent to catmint oil by weight may from about 20:1 to about 1:20, or from about 10:1 to about 1:10, or from about 15:1 to about 1:1, or from about 5:1 to about 1:15, or from about 5:1 to about 1:5, or from about 2:1 to about 1:2, or any range therein. In some embodiments, the ratio of additional antiviral agent to catmint oil by weight may be about 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2.9:1, 2.8:1, 2.7:1, 2.6:1, 2.5:1, 2.4:1, 2.3:1, 2.2:1, 2.1:1, 2:1, 1.9:1, 1.8:1, 1.7:1, 1.6:1, 1.5:1, 1.4:1, 1.3:1, 1.2:1, 1.1:1, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4:, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or any range therein. In some embodiments, the ratio of additional antiviral agent to catmint oil by weight is from about 2:1 to about 1:2. In some embodiments, the ratio of additional antiviral agent to catmint oil by weight is 1:1.Auxiliary agents

[0057] One or more additional auxiliary agents, such as adjuvants, dispersants, wetting agents, lubricants, preservatives, colouring agents (e.g., dyes) odourants, and the like, can also be added where desired to modify the properties of the formulation of the invention as required.Pharmaceutical composition

[0058] It will be appreciated that the formulations of the invention may be prepared in a pharmaceutical composition. The pharmaceutical composition may be in any suitable form, for example, in the form of a liquid, gel, ointment, cream, lotion, emulsion, suspension, solution, spray or aerosol. It will be appreciated that the pharmaceutical composition may include suitable excipients based on the particular dosage form, and may be combined with auxiliary agents (such as preservatives, stabilizers, wetting agents, buffers, or salts) for influencing various properties, for example, shelf life.

[0059] In some embodiments, the pharmaceutical composition is in the form of a sprayable aerosol preparation, wherein the active ingredient(s), preferably in combination with a solid or liquid inert carrier, is packaged in a mixture with a pressurized volatile (e.g., a gaseous propellant, such as freon) or in a squeeze bottle. In some embodiments, the pharmaceutical composition is in the form of an aerosolisable solution, suitable for use in generating an aerosol which comprises the active component(s). In some embodiments, the aerosol is generated by an ultrasonic aerosol generator.

[0060] Without wishing to be bound by any theory, it is understood that ultrasonic aerosol generators utilize high frequency sound waves in order to produce a fine mist of liquid by inducing capillary waves on the liquid surface that subsequently break into small droplets. This method is understood to have a relatively low power consumption, the ability to atomize viscous liquids, and results in the production of a fine mist with a narrow droplet size distribution. In some embodiments, the aerosol has a particle size of from about 1 pm to about 10 pm, about 1.5 pm to about 9 pm, about 2 pm to about 8 pm, about 2 pm to about 7 pm, about 2 pm to about 6 pm, about 2.5 pm to about 5.5 pm or about 3 pm to about 5. pm, or any range in between. In some embodiments, the aerosol has a particle size of at least 1 , 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9 or 9.5 pm, or any amount in between. In some embodiments, the aerosol has a particle size of less than 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or 10 pm, or any amount in between. In some embodiments, the aerosol has a particle size of about 1 , 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or 10 pm, or any amount in between. In some embodiments, the aerosol has a particle size of from about 3 pm to about 5 pm.

[0061] As used herein, the term “target site”, “target location” “target area” or “target space” refer to any area, location or habitat where the prevention, control and / or eradication of a virus is needed or expected to be needed.Methods of use

[0062] In some embodiments, the formulation of the present invention is an antiviral formulation. In some embodiments, there is provided a method of treating or preventing a viral infection, the method comprising the step of administering to a patient in need thereof a formulation according to the invention. In some embodiments, present invention relates to the use of a formulation according to the invention in the manufacture of a medicament for treating or preventing a viral infection. In some embodiments, the viral infection is selected from the group consisting of human immunodeficiency virus (HIV), human herpesviruses (HSV1 and HSV2) and yellow fever virus infection. In some embodiments, the viral infection is a respiratory infection. The respiratory infection may be any respiratory infection for which the formulation would be effective. In some embodiments, the respiratory infection is a coronavirus (e.g. SARS-CoV, SARS-CoV-2 and MERS- CoV), influenza A virus (e.g. subtype H1 N1 and H3N2), influenza B virus, influenza C virus, influenza D virus, or avian influenza virus infection. In some embodiments, the respiratory infection is a coronavirus or influenza virus infection. In some embodiments, the respiratory infection is a SARS-CoV-2 or influenza virus subtype H1 N1 infection.

[0063] Without withing to be bound by any theory, it is understood that formulations according to the invention, when formed into an aerosol and delivered to a target area, are advantageously able to interact with airborne viruses and thereby damage, disrupt or otherwise impact thetransmissibility (also known as infectivity) of said virus. In some embodiments, the formulations according to the invention disrupt the viral envelope and / or cause a reduction in size of the viral particle.

[0064] In some embodiments, there is provided a method of reducing the infectivity of a virus, the method comprising the step of contacting the virus with a formulation according to the invention. In some embodiments, the step of contacting the virus comprises the steps of: a) forming an aerosol comprising the formulation of the invention, and b) delivering the aerosol to a target area.

[0065] The aerosol may be formed by any suitable means e.g. as set out above. In some embodiments, the aerosol is formed by an ultrasonic aerosol generator (also known as an ultrasonic nebulizer, atomizer or diffuser). In some embodiments, the aerosol is formed as an ultrasonically generated vapour. In some embodiments, the aerosol is generated directly at or adjacent to the target area. In other embodiments, the aerosol is generated distal to the target area. In some embodiments, the aerosol is delivered via a ‘stand-alone’ ultrasonic generator. In some embodiments, the aerosol is delivered via an ultrasonic generator which is integrated with existing air-conditioning or humidifying systems. In some embodiments the existing air-conditioning or humidifying systems may be in public, commercial, horticultural, agricultural and / or domestic buildings. In some embodiments, step b) comprises delivering the aerosol to a target area comprising the virus.

[0066] The virus may be any suitable virus, for example, the virus may be a coronavirus (e.g. SARS-CoV, SARS-CoV-2 and MERS-CoV), influenza A virus (e.g. subtype H1 N1 and H3N2), influenza B virus, influenza C virus, influenza D virus, or avian influenza virus, human immunodeficiency virus (HIV), human herpesviruses (HSV1 and HSV2) or yellow fever virus.

[0067] The skilled person will appreciate that the formulations according to the invention (either in solution or as an aerosol) may be delivered to the target area before the virus is present in the target area (i.e. as a preventative or prophylactic) or after the virus is present in the target area. It will be appreciated that the method of forming the formulation into an aerosol and delivering it to a target area may also be referred to as the ‘air-attack’ method. Without wishing to be bound by any theory, it is understood that ultrasonic diffusers are particularly suitable for public, commercial, home, agricultural and horticultural spaces and in particular, for use in enclosed spaces. In some embodiments, the method comprises the step of adding drops, tablets or capsules comprising the formulation to a water reservoir. In some embodiments, the water reservoir is the water reservoir of an existing air-conditioning or humidifying system.DEFINITIONS

[0068] In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set out below. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention only and is not intended to be limiting.

[0069] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one having ordinary skill in the art to which the invention pertains.

[0070] Unless the context clearly requires otherwise, throughout the description and the claims, the terms “comprise”, “'comprising”, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”. For example, a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process or method.

[0071] The transitional phrase "consisting of” excludes any element, step, or ingredient not specified. If in the claim, such would close the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase "consisting of" appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.

[0072] The transitional phrase "consisting essentially of" is used to define a composition, process or method that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the claimed invention. The term "consisting essentially of' occupies a middle ground between "comprising" and "consisting of".

[0073] Where the applicant has defined an invention or a portion thereof with an open-ended term such as "comprising", it should be readily understood that (unless otherwise stated) the description should be interpreted to also describe such an invention using the terms "consisting essentially of" or "consisting of." In other words, with respect to the terms “comprising”, “consisting of”, and “consisting essentially of”, where one of these three terms is used herein, the presently disclosed and claimed subject matter may include the use of either of the other two terms. Thus, in some embodiments not otherwise explicitly recited, any instance of “comprising” may be replaced by “consisting of” or, alternatively, by “consisting essentially of”.

[0074] While reference may be made in this disclosure to the invention comprising a combination of a plurality of elements, it is also understood that this invention is regarded to comprise combinations which omit or exclude one or more of such elements, even if this omission or exclusion of an element or elements is not expressly stated herein, unless it is expressly stated herein that an element is essential to the applicant' s combination and cannot be omitted. It is further understood that the related prior art may include elements from which this invention may be distinguished by negative claim limitations, even without any express statement of such negative limitations herein. It is to be understood, between the positive statements of applicant's invention expressly stated herein, and the prior art and knowledge of the prior art by those of ordinary skill which is incorporated herein even if not expressly reproduced here for reasons of economy, that any and all such negative claim limitations supported by the prior art are also considered to be within the scope of this disclosure and its associated claims, even absent any express statement herein about any particular negative claim limitations.

[0075] As used herein, with reference to numbers in a range of numerals, the terms "about," "approximately" and "substantially" are understood to refer to the range of -10% to +10% of the referenced number, preferably -5% to +5% of the referenced number, more preferably -1 % to + 1 % of the referenced number, most preferably -0 .1 % to +0 .1 % of the referenced number. Moreover, with reference to numerical ranges, these terms should be construed as providing support for a claim directed to any number or subset of numbers in that range. For example, a disclosure of from 1 to 10 should be construed as supporting a range of from 1 to 8, from 3 to 7, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, from 8 to 10, and so forth.

[0076] The terms “preferred” and “preferably” refer to embodiments of the invention that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the invention.

[0077] Unless expressly stated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).

[0078] The term "and / or" used in the context of "X and / or Y" should be interpreted as "X," or "Y," or "X and Y." Similarly, "at least one of X or Y" should be interpreted as "X," or "Y," or "both X and Y."

[0079] The indefinite articles "a" and "an" preceding an element or component of the invention are intended to be non-restrictive regarding the number of instances (i.e. , occurrences) of the element or component. Therefore "a" or "an" should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.

[0080] As used herein, wt.% refers to the weight of a particular component relative to total weight of the referenced composition.

[0081] It will be understood that use of the term “between” herein when referring to a range of numerical values encompasses the numerical values at each endpoint of the range. For example, a temperature of between 80 °C and 150 °C is inclusive of a temperature of 80 °C and a temperature of 150 °C.

[0082] Various features of the embodiments of the invention disclosed herein are, for brevity, described in the context of a single embodiment, but may also be provided separately or in any suitable sub-combination. All combinations of the embodiments are specifically embraced by the illustrative embodiments disclosed herein just as if each and every combination was individually and explicitly disclosed. In addition, all sub-combinations listed in the embodiments describing such variables are also specifically embraced by the present compositions and are disclosed herein just as if each and every such sub-combination was individually and explicitly disclosed herein.

[0083] In the foregoing paragraphs, where various ratios of components have been disclosed. It will be appreciated that these ratios of components can be combined in any disclosed combination. For example, the ratio of A:B (which may be between about 100:1 and 1 :100 or any range therein), may be combined with the ratio of C:D (which may be between about 50:1 and 1 :50 or any range therein), and may be combined with the ratio of E:F (which may be between about 10:1 and about 1 :10 or any range therein).BRIEF DESCRIPTION OF THE DRAWINGS

[0084] The aspects described above, as well as other apparent aspects, advantages, and objectives of the present invention are apparent from the detailed description below in combination with the drawing, in which:

[0085] Fig. 1 shows aerosolisation apparatus for H1 N1 and MHV-1 (A) and disinfectants (B). Aerosols of the viruses and disinfectants were generated through aerosoliser A and aerosoliser B, respectively, and interacted in a cubicle cylinder and booth.

[0086] Fig. 2 shows reduction in the number of H1 N1 and MHV-1 infectious viral particles after treatment with Formulation (1) in solution. Error bars represents the means (±SD) of two independent experiments performed in triplicate. * represents p = 0.025 and ** represents p = 0.014.

[0087] Fig. 3 shows reduction in number of MHV (A) and H1 N1 (B) by aerosolised HCO vapours. Error bars represent the means (±SD) of two independent experiments performed in triplicate. ** represent P < 0.025 and * represent P = 0.002

[0088] Fig. 4 shows transmission electron micrographs of H1N1 virus after interaction with disinfectant: (A,B) PBS-treated control sample shows an intact H1 N1 virus envelope (the roundness of the viral particle and the darker shading demonstrating an intact viral envelope), and (C,D) viruses after exposure to the disinfectant HCO and NHCO, respectively, demonstrate disruption of the lipid envelope and reduction in viral size due to the loss of the viral envelope.

[0089] Fig. 5 shows damage caused by the catmint essential oil formulations to the H1 N1 envelope.DETAILED DESCRIPTION

[0090] The skilled addressee will understand that the invention comprises the embodiments and features disclosed herein as well as all combinations and / or permutations of the disclosed embodiments and features.

[0091] The present invention will now be described with reference to the following examples which should be considered in all respects as illustrative and non-restrictive.

[0092] Example 1 - Preparation of Catmint Oil Formulations

[0093] The following formulations were prepared in per litre of sterile Milli-Q water (sterilised by autoclavation) by dissolving. Formulation (1): hydrogenated catmint (HCO) (0.5 g), bromelain (0.5 g), N-acetylcysteine (0.025 g), Tween 20 (1 g). Formulation (2): non-hydrogenated (NHCO) catmint oil (0.5 g), bromelain (0.5 g), N-acetylcysteine (0.025 g), Tween 20 (1 g). Formulation (3): HCO (0.5 g), + NAC (0.025 g), + Tween 20 (1 g). Formulation (4): bromelain (0.5 g), N- acetylcysteine (0.025 g), Tween 20 (1 g). Formulation (5): N-acetylcysteine (0.025 g), Tween 20 (1 g). The formulations are set out in Table 1.

[0094] Table 1 : Catmint oil formulations

[0095] The hydrogenated catmint oil (HCO) used in the above formulations was obtained commercially as “Refined Oil of Nepeta catena Insect Repellent Technical and Manufacturing Concentrate”, EPA Reg. No 71654-20 from DuPont Chemical Solutions Enterprise P.O. Box 80402 Wilmington, DE 1988-0402

[0096] Example 2 - Antiviral Activity of formulations in solution and aerosolised form

[0097] Respiratory viruses spread through airborne droplets and aerosols, causing highly contagious acute respiratory syndromes in humans. This example shows the antiviral activity of solutions and vapours of various catmint-oil containing formulations against respiratory viruses.

[0098] Summary

[0099] Methods: Formulations were prepared as set out in Example 1. The antiviral activity of formulations with or without catmint oil (CO) in solution or in aerosolised form was determined against influenza virus H1N1 ATCC VR-1469 and mouse hepatitis virus (MHV-1) ATCC / VR261. In solution, both viruses were exposed to CO formulations for 2-3 h. In aerosolised form, H1N1 was exposed to formulations for 2 min in a closed cylinder and MHV-1 for 10 min in a booth. The antiviral effect of the formulations was evaluated by growing H1 N1 in a Madin-Darby canine kidney (MDCK; ATCC-CRL-2936) and MHV-1 in A9 ATCC / CCL 1.4 cells using TCID50 and a plaque assay, respectively. Transmission electron microscopy (TEM) was conducted to investigate the mode of action of the formulations.[000100] Results: In solution, the formulation containing hydrogenated CO (HCO), bromelain, N- acetylcysteine and Tween 20 (Formulation (1)) reduced the viability of H1N1 by 2.6 ± 0.07 logw (p = 0.025) and MHV-1 by 4.5 ± 0.14 logw (p = 0.014) within 2-3 h. In vapourised form, Formulation (1) produced similar antiviral effects against H1 N1, reducing it by 3.00 ± 0.07 logw(p = 0.002) within 2 min, and Formulation (1) produced a 3.00 ± 0.07 log reduction of MHV-1 (p < 0.001) within 10 min (the minimum time needed to detect infective viral particles in the experimental set-ups).Formulation (3) (without bromelain) reduced H1 N1 by 1.57 ± 0.14 logw (p = 0.008) after 2 min and MHV-1 by 1.3 ± 0.04 log (p = 0.057) after 10 min. In the absence of catmint oil (Formulation (4)) or in the absence of catmint oil and bromelain (Formulation (5)), there were only slight reductions in the viability of aerosolised H1 N1 (1.00 ± 0.14 logw, p = 0.046; <1 logw, p = 0.966, respectively) and MHV-1 (1.07 ± 0.02 logw, p = 0.013; 0.16 ± 0.03 logw.p = 0.910, respectively). The TEM analysis showed that the formulation disrupted the H1 N1 envelopes and caused a reduction in size of the viral particles.[000101] Materials - Viruses and Cell Lines[000102] Influenza virus H1 N1 ATCC VR-1469 and mouse hepatitis virus (MHV-1) ATCC / VR261 stocks were prepared prior to testing by growing them in a Madin-Darby canine kidney (MDCK; ATCC-CRL-2936) and A9 ATCC / CCL 1.4 cells, respectively, in Dulbecco’s minimum essential medium (DM EM) containing 10% foetal bovine serum (FBS) and antibiotics (streptomycin sulphate and penicillin G) at 37 °C in a humidified incubator with 5% CO2. For H1 N1 growth, the DMEM was supplemented with tosylamide phenylethyl chloromethyl ketone-treated trypsin (2 pg / mL) (Sigma Aldrich, St Louis MO, USA). Cytopathic effects were visually evident after 3-4 days, and the viruses were then harvested by centrifugation (2000* g for 20 min), aliquoted in 1.5 mL centrifuge tubes and stored at -80 °C. The aliquots were then used in subsequent experiments. The titres of H1 N1 and MHV-1 were determined by TCID50 or plaque assays, respectively, as described below.[000103] In solution[000104] Initial studies demonstrated that the HCO-based formulation (1) dissolved into the DMEM containing 7.5% BSA, as a neutraliser, had no cytotoxic effect on the MDCK or A9 cells. The antiviral activity of the catmint oil formulations was assessed by incubating H1 N1 virus with Formulation (1). Specifically, 1 mL of H1 N1 or MHV-1 solution (1 x 106-7pfu / mL) was mixed with 9 mL of Formulation (1) at room temperature for 2-3 h. After the incubation period, the solution was diluted (10-fold serial dilution) in DMEM containing 7.5% (w / v) bovine serum albumin (BSA), which acted as a neutraliser for the active ingredients. Then, 100 pL of the dilutions were inoculated into a 96-well plate, which had already been seeded with MDCK cells (1 x 104cells / mL) to achieve approximately 80-90% confluency. The virus-inoculated plate was then incubated for 1 h, followed by the addition of 100 pL of fresh DMEM. After further incubation for 3-4 days, the antiviral efficacy of the disinfectant was assessed by determining the TCID50 (50% Tissue Culture Infective Dose) details, as outlined below.[000105] In aerosolised form[000106] An aliquot (4-5 mL) of H1 N1 was aerosolised in a closed cylinder (Figure 1A) in a biosafety cabinet for 2 min at a rate of 2.5 mL per minute using aerosoliser A (containing 100 mL viruses), which generated average aerosol sizes of 3.0 to 5.0 pm. Similarly, 20-25 mL MHV-1 was aerosolised for 10 min in a closed booth with an area of 3 m2(Figure 1 B), for 10 min. Preliminary studies had shown that the minimum times required to detect sufficient infective aerosolised viral particles of both viruses within these experimental set-ups after collection with an Anderson impactor were 2 min and 10 min, respectively. Simultaneously, all the formulations were separately aerosolised at the same rate into the same booth or cylinder from the other aerosoliser B (Figure 1 A, B). The ultrasonically generated vapours of the formulations were allowed to interact for 2 min or 10 min with the H1 N1 and MHV-1 aerosols, respectively, followed by collection for 5 min and 10 min, respectively, using a vacuum pump attached to a 6-stage Anderson impactor containing plates containing 2% agar. The viruses were exposed to aerosolised sterile Milli-Q water as a negative control. Subsequently, the H1 N1 and MHV-1 particles were scraped from the agar plates into 1.5 mL of DMEM and further diluted for quantification by determination of the TCID50 and plaque assay, respectively.[000107] Determination of TCID50[000108] A modified TCID50 method was employed to quantify the H1 N1 particles following treatment with the different formulations. Initially, 100 pL of the virus treated with the different formulation vapours, or with sterile Milli-Q water vapours (as control), were inoculated into a 96- well plate that had been pre-seeded with MDCK cells (1 x 105cells / mL) and had reached approximately 80-90% confluency. The plates were then incubated at 37 °C in a 5% CO2 atmosphere for 1 h, with gentle shaking occurring at 15 min intervals. Subsequently, each well received 100 pL of fresh DMEM and was further incubated at 37 °C in a 5% CO2 environment for 3-4 days. After the incubation period, all the wells of the plate were washed with phosphate buffer saline (PBS, NaCI 8 g / L, KCI 0.2 g / L, Na2HPO41.4 g / L, KH2PO40.24 g / L; pH 7.2) and then stained with 1% crystal violet. Wells exhibiting the loss of MDCK cell monolayers due to the cytopathic effect (CPE) of the virus were considered positive, while wells that retained the MDCK cell monolayer without displaying any signs of CPE were deemed negative. The difference in the viral particle count resulting from the activity of the formulations, compared to the Milli-Q water control aerosols, was determined using the Reed and Muench formula in conjunction with the TCID50 protocol.[000109] Plaque Assay[000110] For titration of infectious MHV-1 , A9 cells were seeded in 12-well tissue culture plates at 5-10 x 105cells per well and allowed to adhere overnight at 37 °C in 5% CO2. After incubation, the culture medium was removed, and the cells were washed with phosphate-buffered saline (PBS,NaCI 8 g / L, KCI 0.2 g / L, Na2HPO41.4 g / L, KH2PO40.24 g / L; pH 7.2) Subsequently, 100 pL of serially diluted virus was inoculated into a well containing A9 cells that had reached approximately 80-90% confluency. The plates were then incubated at 37 °C in a 5% CO2atmosphere for 1 h, with gentle shaking occurring at 15 min intervals. After incubation, the cells were overlaid with 1% agarose (Sigma-Aldrich, Castle Hill, NSW, Australia) and further incubated for 72 h. Following incubation, the cells were fixed with 4% formaldehyde for 2-3 h. The number of viral plaque-forming units (PFUs) from each sample was quantified after staining the cells with 1 % crystal violet (Sigma- Aldrich). The reduction in PFUs for each disinfectant compared to the negative control (water) was calculated.[000111 ] Transmission Electron Microscopy[000112] Transmission electron microscopy was conducted to investigate the mechanism of action of these disinfectant formulations on H1 N1. Briefly, H1 N1 was exposed to Formulations (1) and (2) for 2 h at 37 °C. Following treatment, 10 pL of the treated mixture was applied to a glow- discharged carbon-coated 200 mesh copper grid and allowed to evaporate for 5 min. The samples were subsequently stained with 1 % phosphotungstic acid (pH 6.5) for 30 s to enhance the contrast. After air-drying, the grids were examined using an FEI Tecnai G2 20 transmission electron microscope.[000113] Statistical Analysis[000114] The quantitative data of the virus titres were expressed as the mean and SD values of the logi o reduction value for two separate experiments performed in triplicate. Statistical analysis was performed using Welch’s correction and the unpaired t-test for H1 N1 and one-way ANOVA with Tukey’s test for MHV-1 with GraphPad Prism 8.0.2 (GraphPad Software, La Jolla, CA, USA). Significant differences were accepted at p < 0.05.[000115] Results[000116] Effect of Formulation (1) in Solution[000117] The HCO-based Formulation (1) demonstrated excellent antiviral activity against H1 N1 and MHV-1 in solution. After 2-3 h of incubation, Formulation (1) achieved a 2.6 ± 0.07 logw reduction in H1 N1 virus particles compared to the PBS negative control (p = 0.025; Figure 2). Similarly, for MHV-1 , Formulation (1) resulted in a 4.5 ± 0.14 log reduction in infective particles after the same incubation period (p = 0.014; Figure 2). In the control (PBS-treated) samples, there were viable virus particles that induced infection and produced cytopathic effects in MDCK cells for H1 N1 and A9 cells for MHV-1.[000118] Effect of Formulations in Aerosol Form[000119] The Formulation (1) vapours significantly affected the viability of aerosolised H1 N1 during the 2 min of interaction, resulting in a 3.00 ± 0.14 logw reduction in infective virus particles (p = 0.002; Table 2). Additionally, after vaporising Formulation (2) and allowing it to interact with aerosolised H1 N1 for 2 min, a reduction of 2.34 ± 0.24 log in infective virus particles was observed (p = 0.025). Both Formulation (1) (HCO-based) and Formulation (2) (NHCO-based) exhibited comparable antiviral effects against aerosolised viruses in vaporised form (p > 0.05). Formulation (3), which omitted the bromelain, produced a 1.57 ± 0.14 logw reduction in the viability of infective particles (p = 0.008). The vapours of Formulation (4), which contained bromelain and N- acetylcysteine only, and Formulation (5), which contained only N-acetylcysteine with Tween 20, did not significantly impact the viability of aerosolised H1 N1 (p = 0.046 and p = 0.966, respectively).[000120] Table 2. Reduction in the number of aerosolised H1 N1 particles after treatment with vapourised disinfectant containing vapours of different formulations. Data represent two independent experiments performed in triplicate (±SD).[000121] Given that both Formulation (1) (HCO-based) and Formulation (2) (NHCO-based) produced similar antiviral effects against aerosolised H1 N1 , only Formulation (1) was tested against MHV-1. After 10 min of interaction, the vapours from the HCO-based Formulation (1) resulted in more than a 3.10 ± 0.04 logw reduction in infective virus particles (p < 0.001 ; Table 3). Formulation (3), which included HCO, NAC, and Tween 20, produced a 1.30 ± 0.04 logw reduction after 10 min of interaction with MHV-1. In contrast, Formulation (4), which did not contain HCO or NHCO, demonstrated only slight antiviral activity, reducing the viability of MHV 1.07 ± 0.02 by 1 logw after 10 min (p = 0.013). Formulation (5), containing acetylcysteine along with Tween 20, didnot significantly affect the reduction in viability of aerosolised MHV-1 , as the number of aerosolised viral particles remained unchanged when plated on A9 cells compared to the water-treated control (p = 0.910).[000122] Table 3. Reduction in the number of aerosolised MHV-1 particles after treatment with vapourised disinfectant formulations. Data represent two independent experiments performed in triplicate (±SD).[000123] Transmission Electron Microscopy[000124] The TEM images of the HCO- or NHCO-based formulations and control-treated viral particles are shown in Figure 4. Ultrastructural analysis showed that both formulations directly affected the viral envelope. Figure 4C, D show disrupted viral envelopes (a clear area outside of the virion) after treatment with the HCO- and NHCO-based formulations, respectively. In comparison, in the control samples, the virus particles were well ordered, round, with an area of darker shading outside of virions (Figure 4A,B). Moreover, both formulations also caused a reduction in the size of the viral particle, presumably due to the decomposition of the viral envelope (Figure 4C,D).[000125] Discussion[000126] The above example demonstrates the surprising antiviral effect that formulations according to the invention demonstrated on aerosolised H1 N1 virus and coronavirus particles, effectively neutralising them in the air. Without wishing to be bound by any theory, it is believed that the observed antiviral effect may be attributed to the action of essential oils (EOs) on the viral envelope, as evidenced by the reduction in the virion particle size from the loss of the viral envelope of H1 N1 during the TEM analysis. Whilst some previous studies have shown that some individual compounds, when used singly, of the formulations can have antiviral activity in solution, the current invention surprisingly demonstrates the ability of combinations in vapour form to reduce theinfectivity of a strain of influenza virus and norovirus. This is uniquely advantageous as respiratory viruses primarily spread through aerosols or direct / indirect contact, such as touching contaminated objects, with nasal and throat secretions of infected individuals; therefore, the ability of antiviral compounds to prevent the subsequent infectivity of the virus from aerosols may reduce the spread of the virus.[000127] In the present invention, vapours of both the HCO- or NHCO-based formulations (1 and 2) showed excellent antiviral activity against H1 N1 aerosols and reduced their infectivity by decreasing the viability by >2.5 logio PFU / mL in 2 min. Similarly, the HCO-based formulation (1) vapours inactivated aerosolised MHV-1 by >3 logw PFU / mL within 10 min. Earlier studies have shown that electrolysed saline containing sodium hypochlorite or mouth washes can inactivate bioaerosols of the equine arteritis virus, and feline calicivirus, respiratory syncytial virus A, parainfluenza 4, influenza B, rhinovirus / enterovirus, SARS-CoV-2 and SARS-CoV-2 generated from saliva. In a previous study, tea tree and bergamot oil vapours inactivated 2.35 logw H1 N1 viruses in 30 min. The differences observed in the virus inactivation timeline may be due to the use of dried viruses in the previous study compared to aerosolised viruses in the present invention. Without wishing to be bound by any theory, it is hypothesised that viruses in aerosolised form or in solution can be inactivated more rapidly by disinfectants than those dried on surfaces. An earlier study using a gel containing various essential oils (such as eucalyptol, myrcene, limonene, terpinene, and cymene) achieved only a 0.3 log reduction in MHV-1 infectious virions in 10 min. Without wishing to be bound by any theory, this difference in the efficacy of essential oil formulations may be attributed to the gel having to release the essential oils via evaporation, rather than as in the present invention, where the formulations were aerosolised.[000128] The data set out above suggest that the catmint oil was the predominant antiviral in the formulation, as Formulation (3), which did not contain bromelain but contained catmint, NAC and Tween 20 and two other ingredients, produced better levels of viral reduction compared to Formulation (4), which contained bromelain, NAC and Tween 20. The number of H1 N1 viruses in the control samples remained consistent, except for the samples used against Formulation (1), where a higher initial number of viruses were used for the test and control. Formula (1) was therefore tested against an approximately 1 Iog10 PFU / mL greater number of viruses than the other formulas. Whilst this difference resulted in a greater statistical difference for its effect on H1 N1 , it does not diminish the effect of catmint oil on H 1 N 1.[000129] The TEM analysis indicated that Formulations (1) and (2) advantageously directly impacted the virions, disrupting the lipid bilayers of H1 N1. Without wishing to be bound by any theory, it is believed that due to their lipophilic nature, essential oils (EOs) can integrate into the lipid bilayer of viral envelopes. The mechanism of action of EOs may be similar to quaternaryammonium compounds, which kill viruses by damaging the viral envelope. Additionally, EO vapours may act through non-specific intercalation within the viral lipid bilayer, leading to the disorganisation and removal of surface glycoproteins such as hemagglutinin (HA) and neuraminidase (NA), ultimately compromising the viral envelope. Without wishing to be bound by any theory, it is understood that the antiviral efficacy of EOs against H1N1 and MHV-1 may be attributed to active components such as nepetalactone, geraniol, a-pinene, sabinene, p-pinene, 1- cyclohexen-1-yl-methyl ketone, triplal, thymol, nepetalactone caryophyllene, a-humulene, dodecenol, spathulenol, and dimethyl-2-undecane, which have been detected in catmint oil.[000130] The present examples demonstrate that the antiviral effect of Formulations (1) and (2) could be significantly enhanced by the addition of bromelain. Bromelain has a number of enzymes that serve a variety of functions, including proteases and glycosidases. It is understood that bromelain can inactivate H1 N1 virus by cleavage of the hemagglutinin (HA) protein at the C- terminus of the HA2 region, and SARS-CoV-2 by breaking the glycosidic linkages between the spike glycoprotein and envelope protein of SARS-CoV-2. Without wishing to be bound by any theory, it is believed that due to the differences in the modes of action of catmint essential oil and bromelain, they acted synergistically against both viruses.[000131] The other components of the above formulations, N-acetylcysteine and Tween 20 (i.e. polysorbate 20), had no antiviral effect when used without catmint oil, as seen Formulation (5), which contained only these components.[000132] The electronic diffuser produced aerosols ranging from 2 to 5 pm in size. This specific size range is advantageous for evaluating the antiviral effects against aerosolised virus particles. Infectious virus particles and viral RNA have been detected in aerosol particles smaller than 5 pm, which can remain airborne for extended periods and reach deep into the lungs. Aerosols of this size are implicated in airborne viruses, including the influenza virus and SARS-CoV. The present example demonstrates that vapours of the catmint oil formulations could inactivate the aerosols of these viruses of a size < 5 pm. This size range, observed for virus-containing aerosols, can also be applied to other instruments; for example, those used in dental procedures, after confirming the number of viruses, because those procedures may have a low number of viruses.[000133] Conclusions[000134] Both hydrogenated and non-hydrogenated catmint-oil-based formulations reduced the number of viral particles of type A influenza virus H1N1 and mouse hepatitis virus (MHV-1; a surrogate of coronavirus) in solution and vaporised form. Without wishing to be bound by any theory, it is believed that the catmint essential oils and bromelain acted together against H1N1 andkilled it by disorganising and disrupting the viral envelope and are likely to act similarly against MHV-1. A possible mechanism of envelope disruption is set out in Figure 5.[000135] Other embodiments of the invention may be found in the following paragraphs:[000136] 1 . The invention fills a need to lower or fully destroy the viral, bacterial and fungal loads within enclosed spaces to improve human, animal and plant health. This need has been confirmed by the WHO.[000137] 2. Naturally and synthetically based anti-viral, anti-bacteria and anti-fungi substances, mixed in water and released via ultrasonic vapourisation into the air of enclosed spaces.[000138] 3. Small activated water-based particles appear to attach to the viral, bacterial and fungal particles.[000139] 3a. In the case of viruses it appears that the lipid envelope is ruptured and virus becomes unviable.[000140] 4. The active water-based solutions may be composed of: Pyrethrum / Pyrethrin, Bromelain, NAC, HCO(hydrogenated catmint oil), NCO(non-hydrogenated catmint / catnip oil) and Tween 20 - Tween 80 in varying formulations.[000141] 5. In some embodiments, active percentages range from and include 0.001 % to 2% by weight.[000142] 6. After vapourising the formulation into ambient air, fine mist particles appear to attach to the viral, bacterial and fungal particles and be active for hours, depending on the environmental conditions, after which residue will settle on furniture, floors, etc., where it will remain active as fomite for some time. In some embodiments, the halve life of the compositions of the invention is up to 6 hours.[000143] 7. Ultrasonic distribution of the formulations can be via ‘stand-alone’ equipment, integrated with existing air-conditioning or humidifying systems, in public, commercial, horticultural, agricultural and domestic buildings.[000144] 8. The ‘air-attack’ method can be achieved via suitable ultrasonic diffusers for public, commercial, home, agricultural and horticultural enclosed spaces; for these applications, drops, tablets or capsules can be added to the water reservoir to activate the systems.[000145] Although the invention has been described with reference to specific examples, it will be appreciated by those skilled in the art that the invention may be embodied in many other forms,and in particular features of any one of the various described examples may be provided in any combination in any of the other described examples. Various modifications and alterations to this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention. It should be understood that this invention is not intended to be unduly limited by the illustrative embodiments and examples set forth herein and that such examples and embodiments are presented by way of example only with the scope of the invention intended to be limited only by the claims set forth herein as follows.

Claims

CLAIMS1. A formulation comprising: catmint oil; a proteolytic enzyme; an antioxidant; a surfactant; and a solvent.

2. The formulation according to claim 1, wherein the catmint oil is derived from a plant of the Nepeta genus, preferably Nepeta nuda or Nepeta cataria, and is selected from the group consisting of: hydrogenated catmint oil (HCO) and non-hydrogenated catmint oil (NHCO) or a mixture thereof.

3. The formulation of claim 1 or claim 2, wherein the catmint oil comprises one or more of the following: a-pinene, p-pinene, p-cymene, limonene, 1,8-cineole, (E)- -ocimene, trans- pinocarveol, lavandulol, 4aa,7a,7aa-nepetalactone, 4aa,7a,7a -nepetalactone, 4aa,7p,7aa-nepetalactone, (E)-caryophyllene, (E,Z)-iridolactone, a-humelene, dehydronepetalactone and coryophyllene oxide.

4. The formulation according to any one of the preceding claims, wherein the catmint oil is present in an amount from about 0.0125 wt% to about 0.15 wt%.

5. The formulation according to any one of the preceding claims, wherein the antioxidant is present in an amount from about 0.0010 wt% to about 0.005 wt%.

6. The formulation according to any one of the preceding claims, wherein the surfactant is present in an amount from about 0.05 wt% to about 0.15 wt%.

7. The formulation according to any one of the preceding claims, wherein the proteolytic enzyme is selected from the group consisting of bromelain, papain, trypsin and chymotrypsin.

8. The formulation according to any one of the preceding claims, wherein the antioxidant is N-acetylcysteine.

9. The formulation according to any one of the preceding claims, wherein the surfactant is a nonionic surfactant.

10. The formulation according to claim 9, wherein the surfactant is selected from the group consisting of: polysorbate 20 and polysorbate 80.

11. The formulation according to any one of the preceding claims, wherein the proteolytic enzyme is present in an amount from about 0.025 wt% to about 0.075 wt%.

12. The formulation according to any one of the preceding claims, wherein the solvent is water.

13. A formulation comprising: catmint oil; an antioxidant; a surfactant; and a solvent.

14. A formulation comprising: hydrogenated catmint (HCO) or non-hydrogenated (NHCO) catmint oil; bromelain;N-acetylcysteine; and polysorbate 20.

15. A formulation comprising: hydrogenated catmint (HCO) (about 0.05 wt%); bromelain (about 0.05 wt%),N-acetylcysteine (about 0.0025 wt%), polysorbate 20 (about 0.1 wt%), and water.

16. A formulation comprising: non-hydrogenated (NHCO) catmint oil (about 0.05 wt%), bromelain (about 0.05 wt%),N-acetylcysteine (about 0.0025 wt%), polysorbate 20 (about 0.1 wt%), and water.

17. A formulation comprising:HCO (about 0.05 wt%),N-acetylcysteine (about 0.0025 wt%), polysorbate 20 (about 0.1 wt%), and water.

18. A pharmaceutical composition comprising the formulation of any one of the preceding claims.

19. An aerosol comprising the formulation according to any one of claims 1-17.

20. Use of a formulation according to any one of claims 1-17 in the manufacture of a medicament for treating or preventing respiratory infection.

21. A method of treating or preventing respiratory infection, the method comprising the step of administering to a patient in need thereof a formulation according to any one of claims 1- 17 or the pharmaceutical composition of claim 18.

22. The use according to claim 20, or the method according to claim 21, wherein the medicament is in aerosolised form.

23. The aerosol of claim 19 or the use of claim 22 or the method of claim 22, wherein the aerosol is formed as an ultrasonically generated vapour.

24. A method of reducing the infectivity of a virus, the method comprising the step of contacting the virus with a formulation according to any one of claims 1-17 or the pharmaceutical composition of claim 18, wherein the virus is an influenza virus or a coronavirus.

25. The method according to claim 24, wherein contacting the virus comprises the steps of: a) forming an aerosol comprising the formulation according to any one of claims 1-17 or the pharmaceutical composition of claim 18, and b) delivering the aerosol to a target area comprising the virus.

26. The method according to claim 25, wherein in step b) the aerosol is delivered via a ‘standalone’ ultrasonic generator, or an ultrasonic generator which is integrated with existing air- conditioning or humidifying systems.

27. The method according to claim 24, wherein the method comprises the step of adding drops, tablets or capsules comprising the formulation to a water reservoir.

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