WO2022248858A1

WO2022248858A1 - Formulation

Info

Publication number: WO2022248858A1
Application number: PCT/GB2022/051328
Authority: WO
Inventors: Patrick Stephenson; Calum JACKSON; Stephen Dimmer
Original assignee: Oxoid Limited
Priority date: 2021-05-25
Filing date: 2022-05-25
Publication date: 2022-12-01
Also published as: GB2607285A; GB202107439D0

Abstract

Provided herein is an aqueous formulation for inactivating a pathogen. The aqueous formulation comprises an anionic surfactant in a concentration of from about 15 mM to about 70 mM, a buffer providing a pH of from about 2 to about 4.2, and a polynucleotide stabiliser in a concentration of from about 1 mM to about 200 mM. Also provided is a solid mixture comprising an anionic surfactant in an amount of from about 50% to about 70% by weight; a buffer in an amount of from about 20% to about 30% by weight; and a polynucleotide stabiliser in an amount of from about 2% to about 20% by weight. The aqueous formulation and solid mixture may be used for the inactivation of pathogens, for example viruses, and for preserving DNA or RNA. Methods of identifying pathogen may also utilise the aqueous formulation and solid mixture. The aqueous formulation or solid mixture may be provided in a container, e.g. for a kit.

Description

FORMULATION [0001] This invention relates to a formulation for inactivating a pathogen, and more particularly to a formulation comprising an anionic surfactant, a buffer and a polynucleotide stabiliser. The invention also relates to a method of inactivating a pathogen. Also provided are uses of the formulations for the inactivation of pathogens, for example viruses, and for preserving DNA or RNA. BACKGROUND [0002] Infectious disease testing is an important tool in modern medicine. Interest in this field has grown substantially following the emergence of coronavirus disease 2019 (COVID-19) as a global pandemic. Caused by the SARS-CoV-2 virus, COVID-19 has caused death or severe illness in millions of people worldwide and significantly impacted global economies. Accordingly, health authorities worldwide have employed molecular testing in an attempt to bring the pandemic under control. [0003] Molecular detection of infectious diseases using amplification methods such as PCR requires the collection of a sample which contains infectious viruses, bacteria or fungi. These pathogens can remain viable in the sample, posing an infection risk to those handling it during transport to, or within, the laboratory. For that reason, it is desirable to inactivate the sample as soon as possible to remove the risk of infection whilst maintaining the structure of target genetic material. Without inactivation, samples in the laboratory, especially those containing respiratory or high-containment pathogens, need to be handled inside a safety cabinet, limiting workspace and throughput. It is also important that the sample collection and inactivation method avoid (or at least minimise) degradation of the nucleic acid material, to ensure efficient molecular detection. [0004] There are several known methods for inactivation of biological materials. The most commonly used are heat-inactivation and chemical inactivation (see, e.g., “Guidelines on viral inactivation and removal procedures intended to assure the viral safety of human blood plasma products”, WHO Technical Report, Series No.924, 2004, Annex 4; E. Patterson et al., The Journal of Infectious Diseases, Volume 222, Issue 9, 1 November 2020, Pages 1462–1467; G. Kampf et al., Journal of Hospital Infection, 2020, 105, 348- 349). Whilst effective, both heat and chemical inactivation add an extra time-consuming step to the laboratory workflow. [0005] Collection and transport media are now available that chemically inactivate the pathogen within the sample tube before arrival at the laboratory. Most of these media utilise chemicals that have historically been used in protein study or nucleic acid extraction processes, such as sodium dodecyl sulphate and guanidine isothiocyanate (see, e.g., R. Boom et al., Journal of Clinical Microbiology, 1990, 28, 3, 495-503). However, these known media formulations contain these compounds at concentrations that are considered toxic, corrosive, irritant or harmful to the environment and therefore must be handled cautiously. For example, a commonly used chemical inactivator, guanidine isothiocyanate (see, e.g., US8293467 B2, US9683256 B2), releases toxic cyanide gas if mixed with bleach or oxidisers (“Transport Media Safety Risk - Use Compatible Transport Media with SARS-CoV-2 Tests that Use Bleach - Letter to Clinical Laboratory Staff and Health Care Providers”, U.S Food and Drug Administration, 6 April 2020, accessed 21 May 2021 at https://www.fda.gov/medical-devices/letters-health-care-providers/transport-media-safety- risk-use-compatible-transport-media-sars-cov-2-tests-use-bleach-letter). [0006] There is accordingly a need to develop further formulations for inactivating pathogens. It is an object of the invention to develop an effective means and methods for inactivating pathogens (e.g. SARS-CoV-2) which is non-hazardous and/or capable of preserving the structure of the pathogenic genetic material during transport to enable molecular detection of infectious diseases. BRIEF SUMMARY OF THE DISCLOSURE [0007] In accordance with a first aspect of the present invention there is provided an aqueous formulation for inactivating a pathogen, the aqueous formulation comprising: an anionic surfactant in a concentration of from about 15 mM to about 70 mM; a polynucleotide stabiliser in a concentration of from about 1 mM to about 200 mM; and a buffer providing a pH of from about 2 to about 4.2. [0008] A second aspect of the invention provides a use of an aqueous formulation of the first aspect for the inactivation of a pathogen, optionally wherein the use further comprises the preservation of pathogen polynucleotides. [0009] A third aspect of the invention provides a use of an aqueous formulation of the first aspect for the preservation of pathogen polynucleotides. The polynucleotide may be RNA or DNA. The polynucleotide may be RNA. The polynucleotide may be DNA. [0010] A fourth aspect of the invention provides a method of inactivating a pathogen, the method comprising contacting a sample containing the pathogen with a formulation of the first aspect. [0011] A fifth aspect of the invention comprises a method of preserving pathogen polynucleotides, the method comprising contacting a sample containing the pathogen with a formulation of the first aspect to provide a contacted sample, and optionally storing the contacted sample. [0012] A sixth aspect of the invention provides a solid mixture comprising: an anionic surfactant in an amount of from about 50% to about 70% by weight; a buffer in an amount of from about 20% to about 30% by weight; and a polynucleotide stabiliser in an amount of from about 2% to about 20% by weight. [0013] A seventh aspect of the invention provides a use of a solid mixture of the sixth aspect for the inactivation of a pathogen. The use comprises contacting an aqueous sample containing the pathogen with the solid mixture. The use may further comprise the preservation of pathogen polynucleotides. [0014] An eighth aspect of the invention provides a use of solid mixture of the sixth aspect for the preservation of pathogen polynucleotides. The use comprises contacting an aqueous sample containing the pathogen with the solid mixture. The polynucleotide may be RNA or DNA. The polynucleotide may be RNA. The polynucleotide may be DNA. [0015] A ninth aspect of the invention provides a method of inactivating a pathogen, the method comprising contacting an aqueous sample containing the pathogen with a solid mixture of the sixth aspect. [0016] A tenth aspect of the invention comprises a method of preserving pathogen polynucleotides, the method comprising contacting an aqueous sample containing the pathogen with a solid mixture of the sixth aspect to provide a contacted sample, and optionally storing the contacted sample. [0017] An eleventh aspect of the invention provides a method of identifying a pathogen, comprising: contacting a sample containing a suspected pathogen with an aqueous formulation of the first aspect to provide a sample solution comprising suspected pathogen polynucleotides; storing and/or transporting the sample solution; separating the suspected pathogen polynucleotides from the solution; subjecting the suspected pathogen polynucleotides to a detection process, and identifying said suspected pathogen, if present, based on the detected pathogen polynucleotides. [0018] A twelfth aspect of the invention provides a method of identifying a pathogen, comprising: contacting an aqueous sample containing a suspected pathogen with a solid mixture of the fifth aspect to provide a sample solution comprising suspected pathogen polynucleotides; storing and/or transporting the sample solution; separating the suspected pathogen polynucleotides from the solution; subjecting the suspected pathogen polynucleotides to a detection process, and identifying said suspected pathogen, if present, based on the detected pathogen polynucleotides. [0019] A thirteenth aspect of the invention provides a kit comprising: a container comprising an aqueous formulation of the first aspect or a solid mixture of the sixth aspect; and optionally a sterile swab and/or funnel. BRIEF DESCRIPTION OF THE DRAWINGS [0020] Embodiments of the invention are further described hereinafter with reference to the accompanying drawings, in which: Figure 1 is a graphical representation of the SARS-CoV-2 virus structure (see H.F. Florindo et al., Nat. Nanotechnol., 15, 630–645, 2020) Figure 2 shows the interaction of detergent sodium dodecyl sulfate (SDS) with lipid envelopes: (a) illustrates a membrane structure in the absence SDS; (b) illustrates intercalation of detergent monomers into the membrane structure; and (c) illustrates the situation when detergent monomers have solubilised the membrane proteins. (see A. Anandan and A. Vrielink, (2016), ‘Detergents in Membrane Protein Purification and Crystallisation’ in I. Moraes, The Next Generation in Membrane Protein Structure Determination, vol 922, Springer, pages 13-28) DETAILED DESCRIPTION [0021] The abbreviations used herein have their conventional meaning within the chemical and biological arts. [0022] Throughout the description and claims of this specification, the words “comprise” and “contain” and variations of them mean “including but not limited to”, and they are not intended to (and do not) exclude other moieties, additives, components, integers or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise. [0023] Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

[0024] The reader's attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

[0025] For the avoidance of doubt, it is hereby stated that the information disclosed earlier in this specification under the heading “Background” is relevant to the invention and is to be read as part of the disclosure of the invention.

[0026] All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control.

DEFINITIONS

[0027] The following explanations of terms and methods are provided to better describe the present disclosure and to guide those of ordinary skill in the art in the practice of the present disclosure.

[0028] The term “alkali metal” refers to an element from Group 1 of the periodic table, i.e. lithium, sodium, potassium, rubidium, caesium, and francium. Compounds of the disclosure that comprise an alkali metal may comprise lithium, sodium, potassium, rubidium, or caesium. For example, such a compound may comprise lithium, sodium, or potassium; e.g. the compound may comprise sodium.

[0029] The term “buffer” in the present disclosure refers to a conjugate pair comprising of a Brønsted-Lowry acid (HA) and its conjugate Brønsted-Lowry base (A^'). When in solution, the buffer resists change in pH when small amounts of an acid or base are added over a certain range or when the solution is diluted. The amount of resistance to change in pH is dependent on the amount of buffer present. Typically, the buffers of the present invention are acidic buffers comprising an acid and a salt. In these acidic buffers, molecules HA and ions A^' are present. When acid is added, the additional protons are removed by the ions A^'. When base is added, the additional hydroxide ions are removed by reaction with undissociated acid HA:

A- + H⁺ → HA

0H- + HA → A- + H₂0 As a result, the hydrogen ion concentration does not change during dilution of the buffer, and so the buffer will maintain a stable pH. The pH range that a given buffer will maintain is dependent on the pK_a of the given HA. [0030] The term “% w/v” refers to the percentage weight of a particular component per unit volume of solution:

[0031] The term “% by weight” refers to the percentage weight of a particular component per unit weight. For example, the % by weight of a solid represents the percentage of the weight that the component is of the total amount of solid. [0032] The concentration (i.e. molarity) of each component of the formulation in mol/L (M) can be calculated based on the % w/v value using the formula below:

[0033] The term “inactivation” of or “inactivating” a pathogen refers to a process of enhancing safety in which the pathogen is intentionally “killed”. The level of inactivation is typically expressed using log reduction factor (LRF), which refers to a quantity of pathogen, expressed on a log 10 scale that is inactivated. For example, an LRF of 4 comprises a 10,000 reduction factor, corresponding to inactivation of 99.99% of the pathogen. Inactivation may comprise > 4 LRF, e.g. inactivation may comprise > 5 LRF. LRF may be measured using a suitable method for the pathogen, for example, using a viral plaque assay, a bacterial plaque assay, or TCID₅₀ assay (where TCID₅₀ is defined as the amount of pathogen that causes the death of 50% of cells). Exemplary viral plaque assay protocols for determining the LRF are described in E. J. Mendoza et al. (Curr. Protoc. Microbiol., 2020, 57, 1) and N. Bracci et al. (PeerJ, 2020, 8, 10639). Exemplary TCID₅₀ assay protocols for determining the LRF are described in C. M. Coleman et al. (Curr. Protoc. Microbiol., 2015, 37, 15E.2.1 - 15E.2.9) and S. J. Smither et al. (Journal of Virological Methods, 2013, 193, 565-571). [0034] The term “hazardous” refers to a substance, mixture of substances, or a process involving substances that, under production, usage, or disposal conditions, make it capable of causing adverse effects to non-pathogenic organisms, depending on the degree of exposure. Whether a substance or mixture of substances are hazardous may be dependent on concentration. An example of the minimum concentrations at which particular substances or mixture of substances may be considered hazardous are disclosed in REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008 (the entirety of which is incorporated herein by reference). For example, Table 3.3.3 on page 138 of REGULATION (EC) No 1272/2008 (the content of which is incorporated herein by reference), specifies generic concentration limits of ingredients classified as skin corrosion (Category 1, 1A, 1B or 1C) and/or serious eye damage (Category 1) or eye irritation (Category 2), that trigger classification of the mixture as serious eye damage/eye irritation. When a substance is not hazardous, it may be referred to as “non-hazardous”. [0035] The terms “nucleic acid molecule(s)” or “polynucleotide(s)” refers to any compound(s) and/or substance(s) that comprise a polymer of nucleotides. Each nucleotide is composed of a base, specifically a purine- or pyrimidine base (i.e., cytosine (C), guanine (G), adenine (A), thymine (T) or uracil (U)), a sugar (i.e., deoxyribose or ribose), and a phosphate group. Often, the nucleic acid molecule is described by the sequence of bases, whereby said bases represent the primary structure (linear structure) of a nucleic acid molecule. The sequence of bases is typically represented from 5’ to 3’. Herein, the term nucleic acid molecule encompasses deoxyribonucleic acid (DNA) including, e.g., complementary DNA (cDNA) and genomic DNA, ribonucleic acid (RNA), e.g. messenger RNA (mRNA), synthetic forms of DNA or RNA, and mixed polymers comprising two or more of these molecules. The nucleic acid molecule can be linear or circular. In addition, the term nucleic acid molecule includes both, sense and antisense strands, as well as single stranded and double stranded forms. Moreover, the herein described nucleic acid molecule can contain naturally occurring or non-naturally occurring nucleotides. Examples of non-naturally occurring nucleotides include modified nucleotide bases with derivatized sugars or phosphate backbone linkages or chemically modified residues. [0036] The term “pathogen” refers to any organism which causes a disease. The organism may be a virus, bacterium, fungus, or a parasite. The pathogen may be a virus, for example a coronavirus, a rotavirus, a norovirus, an enterovirus, a hepatitis virus, a herpes virus, a papilloma virus, an arbovirus (e.g. West Nile virus, Zika virus, Dengue virus), an ebolavirus, an orthomyxovirus, a paramyxovirus, a rabies virus, a parecho virus, or a rubella virus. The pathogen may be a bacterium, for example a Clostridium, a Pseudomonas, an Escherichia, a Klebsiella, an Enterococcus, an Enterobacter, a Serratia, a Stenotrophomonas, an Aeromonas, a Morganella, a Yersinia, a Salmonella, a Proteus, a Pasteurella, a Haemophilus, a Citrobacter, a Burkholderia, a Brucella, a Moraxella, a Mycobacterium, a Streptococcus or a Staphylococcus. The pathogen may be a fungus, for example a Candida, a Blastomyces, a Coccidioides, a Paracoccidioides, a Histoplasma, a Cryptococcus, a Trichophyton, a Microsporum, a Mucor, an Aspergillus, a Sporothrix, or a Talaromyces. [0037] The term “polynucleotide stabiliser” refers to a substance that stabilises and protects cellular and/or pathogen RNA or DNA in solution, in particular substances that chelate metal ions and prevent oxidative activity of nuclease enzymes. Exemplary polynucleotide stabilisers include citrates, ethylenediaminetetraacetic acid (EDTA), ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), 1,2- cyclohexylenedinitrilo)tetraacetic acid (CDTA), 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′- tetraacetic acid (BAPTA), 8-hydroxyquinoline, citric acid, tartaric acid, lithium chloride, sodium chloride, and magnesium chloride. [0038] A number of the compounds disclosed herein (e.g. exemplary anionic surfactants, exemplary Brønsted-Lowry base (A-), e.g. exemplary polynucleotide stabilisers) comprise an alkali metal cation, such as sodium. While such compounds may be disclosed with a given alkali metal cation, as the skilled person will appreciate, in aqueous solution the identity of the alkali metal cation does not affect the behaviour of the anion. Thus in such compounds disclosed herein, sodium may be substituted with lithium, potassium, rubidium, or caesium. For example, sodium may be replaced with lithium or potassium. Accordingly, unless the context requires otherwise, disclosure of a compound with any one specific alkali metal cation (such as sodium) also includes disclosure of the corresponding compound with each other specific alkali metal cation (such as lithium, potassium, rubidium, or caesium; e.g. lithium or potassium). FORMULATIONS [0039] In any of the following paragraphs, the term “comprising” may be replaced with the terms “substantially consisting of” or “consisting of” as appropriate. [0040] Formulations of the invention are suitable for the inactivation of pathogens. The formulations described herein comprise (or substantially consist of, or consists of): an anionic surfactant in a concentration of from about 15 mM to about 70 mM; a polynucleotide stabiliser in a concentration of from about 1 mM to about 200 mM; and a buffer providing a pH of from about 2 to about 4.2. [0041] The anionic surfactant may be present in a concentration of at least about 15 mM, at least about 20 mM, at least about 22 mM, or at least about 26 mM. The anionic surfactant may be present in a concentration of no more than about 70 mM, no more than about 60 mM, no more than about 50 mM, no more than about 40 mM, no more than about 35 mM, no more than about 30 mM, no more than about 28 mM, or no more than about 26 mM. [0042] The anionic surfactant may be present in a concentration of from about 15 mM to about 70 mM. The anionic surfactant may be present in a concentration of from about 15 mM to about 50 mM. The anionic surfactant may be present in a concentration of from about 15 mM to about 35 mM. The anionic surfactant may be present in a concentration of from about 15 mM to about 30 mM. The anionic surfactant may be present in a concentration of from about 15 mM to about 28 mM. The anionic surfactant may be present in a concentration of from about 15 mM to about 26 mM. The anionic surfactant may be present in a concentration of from about 20 mM to about 70 mM. The anionic surfactant may be present in a concentration of from about 20 mM to about 50 mM. The anionic surfactant may be present in a concentration of from about 20 mM to about 35 mM. The anionic surfactant may be present in a concentration of from about 20 mM to about 30 mM. The anionic surfactant may be present in a concentration of from about 20 mM to about 28 mM. The anionic surfactant may be present in a concentration of from about 20 mM to about 26 mM. The anionic surfactant may be present in a concentration of from about 22 mM to about 35 mM. The anionic surfactant may be present in a concentration of from about 22 mM to about 30 mM. The anionic surfactant may be present in a concentration of from about 22 mM to about 28 mM. The anionic surfactant may be present in a concentration of from about 24 mM to about 28 mM. The anionic surfactant may be present in a concentration of from about 22 mM to about 26 mM. The anionic surfactant may be present in a concentration of from about 26 mM to about 35 mM. The anionic surfactant may be present in a concentration of from about 26 mM to about 30 mM. The anionic surfactant may be present in a concentration of from about 26 mM to about 28 mM. The anionic surfactant may present in a concentration of about 26 mM. [0043] The anionic surfactant may comprise a species selected from: alkyl sulfates, alkyl ether sulfates, arylalkyl sulfates, alkyl aryl ether sulfates alkyl ester sulfates, alkyl sulfonates, alkyl ether sulfonates, arylalkyl sulfonates, alkyl aryl ether sulfonates, alkyl ester sulfonates, alkyl α-olefin sulfonates, alkyl phosphates, alkyl ether phosphates, arylalkyl phosphates, alkyl aryl ether phosphates, alkyl ester phosphates, alkyl carboxylates, alkylamido carboxylates, alkyl ether carboxylates, arylalkyl carboxylates, alkyl aryl ether carboxylates and alkyl ester carboxylates. The anionic surfactant may comprise a species selected from: alkyl sulfates, alkyl ether sulfates, alkyl aryl ether sulfates alkyl ester sulfates, alkyl sulfonates, alkyl ether sulfonates, alkyl aryl ether sulfonates, alkyl ester sulfonates, alkyl α-olefin sulfonates. The anionic surfactant may comprise a species selected from: alkyl sulfates, alkyl ether sulfates, alkyl aryl ether sulfates, alkyl ester sulfates. The anionic surfactant may comprise a species selected from: alkyl sulfates, alkyl ether sulfates. The anionic surfactant may comprise an alkyl sulfate species. The anionic surfactant may comprise an alkyl ether sulfate species. The anionic surfactant may comprise an alkyl sulfonate species. [0044] The anionic surfactant may comprise a C_4-24 alkyl sulfate, a C_4-24 alkyl sulfonate or a C_4-24 alkyl ether sulfate. The anionic surfactant may comprise a C_6-24 alkyl sulfate, a C_6-24 alkyl sulfonate or a C_6-24 alkyl ether sulfate. The anionic surfactant may comprise a C_8-24 alkyl sulfate, a C_8-24 alkyl sulfonate or a C_8-24 alkyl ether sulfate. The anionic surfactant may comprise a C_8-18 alkyl sulfate, a C_8-18 alkyl sulfonate or a C_8-18 alkyl ether sulfate. The anionic surfactant may comprise a C_10-18 alkyl sulfate, a C_10-18 alkyl sulfonate or a C_10-18 alkyl ether sulfate. The anionic surfactant may comprise a C_10-14 alkyl sulfate, C_10-14 alkyl sulfonate or C_10-14 alkyl ether sulfate. The anionic surfactant may comprise a C_10-14 alkyl sulfate. The anionic surfactant may comprise a C_10-14 alkyl sulfonate. The anionic surfactant may comprise a C10-14 alkyl ether sulfate. The anionic surfactant may comprise a C12 alkyl sulfate. [0045] The anionic surfactant may comprise or may be selected from: alkali metal dodecyl sulfate, alkali metal decyl sulfate, alkali metal octyl sulfate, alkali metal hexyl sulfate, alkali metal butyl sulfate, alkali metal 2-butyloctyl sulfate, alkali metal 2-ethylhexyl sulfate, alkali metal 3,7-dimethyloctyl sulfate, alkali metal lauryl sulfate, alkali metal lauryl sarcosinate, ammonium lauryl sulfate, alkali metal laureth sulfate, ammonium laureth sulfate, alkali metal myreth sulfate, alkali metal pareth sulfate, C14-16 alkyl α-olefin sulfonate, alkali metal dodecylbenzene sulfonate, alkali metal octanesulfonate, alkali metal decanesulfonate, alkali metal nonanesulfonate, alkali metal heptanesulfonate, alkali metal hexanesulfonate, alkali metal pentanesulfonate, alkali metal butanesulfonate, alkali metal stearate, dioctyl alkali metal sulfosuccinate. The anionic surfactant may comprise or may be selected from: sodium dodecyl sulfate, sodium decyl sulfate, sodium octyl sulfate, sodium hexyl sulfate, sodium 2-butyloctyl sulfate, sodium 2-ethylhexyl sulfate, sodium 3,7- dimethyloctyl sulfate, sodium lauryl sulfate, sodium lauryl sarcosinate, ammonium lauryl sulfate, sodium laureth sulfate, ammonium laureth sulfate, sodium myreth sulfate, sodium pareth sulfate, C14-16 alkyl α-olefin sulfonate, sodium dodecylbenzene sulfonate, sodium octanesulfonate, sodium decanesulfonate, sodium nonanesulfonate, sodium heptanesulfonate, sodium hexanesulfonate, sodium pentanesulfonate, sodium butanesulfonate, sodium stearate, dioctyl sodium sulfosuccinate. Preferably, the anionic surfactant comprises or is sodium dodecyl sulfate. [0046] Alternatively, the anionic surfactant may be selected from any of the anionic surfactant species identified in WO 2006/062835A2 (in particular the anionic surfactant species identified in WO 2006/062835A2 from page 25, line 24 to page 27, line 18), the contents of which are incorporated herein by reference. [0047] Without wishing to be bound by theory, sodium dodecyl sulfate in an amount of about 35 mM (~ 1% w/v) and higher is considered to be hazardous to the user. It is noted that sodium dodecyl sulfate is considered a Category 1 hazard for serious eye damage/eye irritation, which according to Table 3.3.3 on page 138 of REGULATION (EC) No 1272/2008 (the content of which is incorporated herein by reference) may be hazardous at a concentration of greater than 1%. Accordingly, in some preferred embodiments the anionic surfactant may comprise (or substantially consist of, or consist of) sodium dodecyl sulfate in a concentration of no more than about 35 mM. The anionic surfactant may comprise sodium dodecyl sulfate in a concentration of from about 15 mM to about 35 mM. The anionic surfactant may comprise sodium dodecyl sulfate in a concentration of from about 20 mM to about 30 mM. The anionic surfactant may comprise sodium dodecyl sulfate in a concentration of from about 22 mM to about 28 mM. The anionic surfactant may comprise sodium dodecyl sulfate in a concentration of about 26 mM. [0048] The anionic surfactant may be sodium dodecyl sulfate in an amount of no more than about 1% w/v. The anionic surfactant may be sodium dodecyl sulfate in an amount of from about 0.5% to about 1% w/v, e.g. from about 0.6% to about 1% w/v, from about 0.7% to about 1% w/v, from about 0.8% to about 1% w/v, or from about 0.9% to about 1% w/v. The anionic may be sodium dodecyl sulfate in an amount of from greater than 0.5% to less than 1% w/v, e.g. from greater than 0.6% to less than 1% w/v, from greater than 0.7% to less than 1% w/v, from greater than 0.8% to less than 1% w/v, from greater than 0.9% to less than 1% w/v. [0049] The anionic surfactant may be sodium dodecyl sulfate in an amount of from about 0.5% to about 0.95% w/v, from about 0.5% to about 0.9% w/v, from about 0.5% to about 0.85% w/v, from about 0.5% to about 0.8% w/v, or from about 0.5% to about 0.75% w/v. The anionic surfactant may be sodium dodecyl sulfate in an amount of from about 0.6% to about 0.95% w/v, from about 0.6% to about 0.9% w/v, from about 0.6% to about 0.85% w/v, from about 0.6% to about 0.8% w/v, or from about 0.6% to about 0.75% w/v. The anionic surfactant may be sodium dodecyl sulfate in an amount of from about 0.7% to about 0.95% w/v, from about 0.7% to about 0.9% w/v, from about 0.7% to about 0.85% w/v, from about 0.7% to about 0.8% w/v, or from about 0.7% to about 0.75% w/v. The anionic surfactant may be sodium dodecyl sulfate in an amount of about 0.75% w/v. [0050] It has been shown that high and low pH can affect the viability of pathogens, in particular SARS coronaviruses, however this effect is temperature dependent (M.E.R. Darnell, et al., J. Virol. Methods, 2004 Oct; 121(1): 85–91). In addition, pH control alone is not a reliable method of inactivation as neutralisation is likely to occur due to natural buffering of the sample. We have identified that provision of a low pH in the formulations provided herein, in particular in combination with the specified levels of anionic surfactant, provides a significant level of pathogen inactivation. [0051] The aqueous formulation may have a pH of about from about 3 to about 4.2. The aqueous formulation may have a pH of from about 3 to about 4. The aqueous formulation may have a pH of from about 3.2 to about 3.8. The aqueous formulation may have a pH of from about 3.2 to about 3.6. The aqueous formulation may have a pH of from about 3.4 to about 3.8. The aqueous formulation may have a pH of from about 3.4 to about 3.6. The aqueous formulation may have a pH of about 3.5. [0052] The aqueous formulation may have a pH of at least about 3, about 3.1, about 3.2, about 3.3, about 3.4, or about 3.5. For example, the aqueous formulation may have a pH of at least about 3.4 or about 3.5; e.g. the aqueous formulation may have a pH of at least about 3.5. The aqueous formulation may have a pH of not more than about 4.2, about 4.1, or about 4. The aqueous formulation may have a pH of about from about 3.2 to about 4.2. The aqueous formulation may have a pH of about from about 3.5 to about 4.2. [0053] The anionic surfactant may be sodium dodecyl sulfate and the aqueous formulation may have a pH of from about 3 to about 4. The anionic surfactant may be sodium dodecyl sulfate and the aqueous formulation may have a pH of from about 3.2 to about 3.8. The anionic surfactant may be sodium dodecyl sulfate and the aqueous formulation may have a pH of from about 3.2 to about 3.6. The anionic surfactant may be sodium dodecyl sulfate and the aqueous formulation may have a pH of from about 3.4 to about 3.8. The anionic surfactant may be sodium dodecyl sulfate and the aqueous formulation may have a pH of from about 3.4 to about 3.6. The anionic surfactant may be sodium dodecyl sulfate and the aqueous formulation may have a pH of about 3.5. [0054] The anionic surfactant may be sodium dodecyl sulfate and the aqueous formulation may have a pH of from about 3.2 to about 4.2. The anionic surfactant may be sodium dodecyl sulfate and the aqueous formulation may have a pH of from about 3.5 to about 4.2. [0055] The inventors have surprisingly found that the use of sodium dodecyl sulfate at low pH, e.g. a pH of less than 4.5, has the combined effect of inactivating pathogens while preserving the pathogen polynucleotides. It is believed that a pH of less than 2 will cause degradation of the pathogen nucleotides. Accordingly, the aqueous formulations of the present invention advantageously have pH of from about 2 to about 4.2. Formulations having a pH of about 3.5 may be preferred. [0056] The buffer may comprise or may be selected from a species having a suitable pKa value to maintain a pH of from about 2 to about 4.2 (e.g. from about 3 to about 4.2, from about 3 to about 4, from about 3.2 to about 3.8, or about 3.5). The buffer may comprise or may be selected from: lactate/lactic acid, glycine – hydrochloric acid, acetate/acetic acid and citrate/citric acid. The buffer may comprise or may be selected from: lactate/lactic acid and glycine – hydrochloric acid. The buffer may comprise or may be lactate/lactic acid. The buffer may comprise or may be glycine – hydrochloric acid. [0057] The lactate, acetate and citrate species of the buffer may comprise lactic acid, acetic acid and citric acid respectively and salts thereof. For example, the lactate, acetate and citrate species may comprise alkali metal salts thereof (e.g. lithium, sodium, and/or potassium). Preferably, the buffer is sodium lactate/lactic acid. However, the sodium can be replaced with another alkali metal (e.g. lithium, potassium) as the counter ion where possible. [0058] The buffer may be in a concentration of from about 1 mM to about 500 mM. The buffer may be in a concentration of from about 5 mM to about 150 mM. The buffer may be in a concentration of from about 5 mM to about 100 mM. The buffer may be in a concentration of from about 5 mM to about 50 mM. The buffer may be in a concentration of from about 5 mM to about 25 mM. The buffer may be in a concentration of from about 5 mM to about 15 mM. The buffer may be in a concentration of from about 5 mM to about 10 mM. The buffer may be in a concentration of about 10 mM. [0059] The buffer may be lactate/lactic acid (e.g. sodium lactate/lactic acid) in a concentration sufficient to maintain a pH of from about 2 to about 4.2 (e.g. from about 3 to about 4.2, from about 3 to about 4, from about 3.2 to about 3.8, or about 3.5). The buffer may be lactate/lactic acid (e.g. sodium lactate/lactic acid) in a concentration of from about 5 mM to about 150 mM, from about 5 mM to about 100 mM, from about 5 mM to about 50 mM, from about 5 mM to about 25 mM, from about 5 mM to about 15 mM, or from about 5 mM to about 10 mM. The buffer may be lactate/lactic acid (e.g. sodium lactate/lactic acid) in a concentration of about 10 mM. [0060] Where the buffer is lactate/lactic acid (e.g. sodium lactate/lactic acid), the lactate may be present in an amount of from about 0.03% to about 0.07% w/v (e.g. about 0.05% w/v) and the lactic acid may be present in an amount of from about 0.2% to about 0.25% w/v (e.g. about 0.22% w/v). [0061] The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 200 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 150 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 100 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 50 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 25 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 20 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 15 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 10 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 9 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 8 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 7 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 6 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 5 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 4 mM. The polynucleotide stabiliser may be in a concentration of from about 1 mM to about 3 mM. The polynucleotide stabiliser may be in a concentration of from about 1.2 mM to about 2.8 mM. The polynucleotide stabiliser may be in a concentration of from about 1.5 mM to about 2.5 mM. The polynucleotide stabiliser may be in a concentration of about 2 mM. [0062] The polynucleotide stabiliser may comprise or be selected from: citrate, ethylenediaminetetraacetic acid (EDTA), ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′- tetraacetic acid (EGTA), 1,2-cyclohexylenedinitrilo)tetraacetic acid (CDTA), 1,2-bis(o- aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), 8-hydrozyquinoline, citric acid, tartaric acid, lithium chloride, sodium chloride, and magnesium chloride. Preferably, the polynucleotide stabiliser is citrate (e.g. sodium citrate). [0063] The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 150 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 100 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 50 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 25 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 20 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 15 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 10 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 9 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 8 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 7 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 6 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 5 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 4 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1 mM to about 3 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1.2 mM to about 2.8 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of from about 1.5 mM to about 2.5 mM. The polynucleotide stabiliser may comprise citrate (e.g. sodium citrate) in a concentration of about 2 mM. [0064] The polynucleotide stabiliser may be an RNA stabiliser. Alternatively, the polynucleotide stabiliser may be a DNA stabiliser. [0065] The aqueous formulation may be non-hazardous. For example, the aqueous formulation may comprise each of the anionic surfactant, the polynucleotide stabiliser and the buffer at concentrations below the minimum concentrations at which each of the anionic surfactant, the polynucleotide stabiliser and the buffer may be considered hazardous in accordance with REGULATION (EC) No 1272/2008. [0066] An exemplary aqueous formulation for inactivating a pathogen comprises: an anionic surfactant in a concentration of from about 15 mM to about 35 mM; a polynucleotide stabiliser in a concentration of from about 1 mM to about 3 mM; and a buffer providing a pH of from about 2 to about 4.2. The anionic surfactant, polynucleotide stabiliser and buffer may be as further defined herein. SOLID MIXTURES [0067] Compositions disclosed herein are intended for inactivating a pathogen. This inactivation is typically performed in aqueous solution, e.g. with aqueous formulations provided herein. The aqueous solution may also be obtained by contacting an aqueous sample that may comprise a pathogen with a solid mixture comprising anionic surfactant, buffer and polynucleotide stabiliser. The aqueous sample may be a biological fluid, such as saliva, sputum, bronchial lavage, tracheal aspirate, nasal wash, urine, semen, lacrimal fluid, synovial fluid, blood, serum, plasma, lymph, cerebrospinal fluid, peritoneal dialysis fluid, or pus. In addition, compositions of the disclosure may be provided as solid mixtures for improved handling and/or storage, then contacted with water to form an aqueous formulation, when said aqueous solution is desired. [0068] Accordingly, an aspect of the invention provides a solid mixture comprising: an anionic surfactant in an amount of from about 4% to about 95% by weight; a buffer in an amount of from about 0.4% to about 80% by weight; and a polynucleotide stabiliser in an amount of from about 0.5% to about 70% by weight. The anionic surfactant may be in an amount of from about 40% to about 80% by weight; a buffer in an amount of from about 15% to about 40% by weight; and a polynucleotide stabiliser in an amount of from about 1% to about 30% by weight. [0069] The anionic surfactant may be in an amount of from about 50% to about 70% by weight, from about 55% to about 70% by weight, from about 60% to about 70% by weight, or from about 65% to about 70% by weight. Preferably, the anionic surfactant is in amount of about 70% by weight. [0070] The buffer may be in an amount of from about 20% to about 30% by weight, or from about 22% to about 28% by weight. Preferably, the buffer is in an amount of about 25% by weight. [0071] The buffer may be formulated to provide a pH of from about 2 to about 4.2 when the solid mixture is solubilised in water to provide an aqueous solution with the buffer at a concentration of from about 1 mM to about 500 mM (e.g. at a concentration of from about 5 mM to 100 mM). [0072] The buffer may be formulated to provide a pH of from about 3 to about 4.2 when the solid mixture is solubilised in water to provide an aqueous solution with the buffer at a concentration of from about 1 mM to about 500 mM (e.g. at a concentration of from about 5 mM to 100 mM). [0073] The buffer may be formulated to provide a pH of from about 3.3 to about 4.2 when the solid mixture is solubilised in water to provide an aqueous solution with the buffer at a concentration of from about 1 mM to about 500 mM (e.g. at a concentration of from about 5 mM to 100 mM). [0074] The buffer may be formulated to provide a pH of from about 3.5 to about 4.2 when the solid mixture is solubilised in water to provide an aqueous solution with the buffer at a concentration of from about 1 mM to about 500 mM (e.g. at a concentration of from about 5 mM to 100 mM). [0075] The buffer may be formulated to provide a pH of from about 3 to about 4 when the solid mixture is solubilised in water to provide an aqueous solution with the buffer at a concentration of from about 1 mM to about 500 mM (e.g. at a concentration of from about 5 mM to 100 mM). [0076] The buffer may be formulated to provide a pH of from about 3.5 to about 4 when the solid mixture is solubilised in water to provide an aqueous solution with the buffer at a concentration of from about 1 mM to about 500 mM (e.g. at a concentration of from about 5 mM to 100 mM). [0077] The buffer may be formulated to provide a pH of from about 3.2 to about 3.8 when the solid mixture is solubilised in water to provide an aqueous solution with the buffer at a concentration of from about 1 mM to about 500 mM (e.g. at a concentration of from about 5 mM to 100 mM). [0078] The buffer may be formulated to provide a pH of from about 3.2 to about 3.6 when the solid mixture is solubilised in water to provide an aqueous solution with the buffer at a concentration of from about 1 mM to about 500 mM (e.g. at a concentration of from about 5 mM to 100 mM). [0079] The buffer may be formulated to provide a pH of from about 3.4 to about 3.8 when the solid mixture is solubilised in water to provide an aqueous solution with the buffer at a concentration of from about 1 mM to about 500 mM (e.g. at a concentration of from about 5 mM to 100 mM). [0080] The buffer may be formulated to provide a pH of from about 3.4 to about 3.6 when the solid mixture is solubilised in water to provide an aqueous solution with the buffer at a concentration of from about 1 mM to about 500 mM (e.g. at a concentration of from about 5 mM to 100 mM). [0081] The buffer may be formulated to provide a pH of about 3.5 when the solid mixture is solubilised in water to provide an aqueous solution with the buffer at a concentration of from about 1 mM to about 500 mM (e.g. at a concentration of from about 5 mM to 100 mM). [0082] The polynucleotide stabiliser may be in an amount of from about 2% to about 20% by weight, from about 2% to about 15% by weight, from about 2% to about 10% by weight, from about 2% to about 9% by weight, from about 2% to about 8% by weight, from about 2% to about 7% by weight, from about 2% to about 6% by weight, or from about 2% to about 5% by weight. Preferably, the polynucleotide stabiliser is in an amount of about 5% by weight. [0083] In an exemplary solid mixture, the anionic surfactant is in an amount of from about 50% to about 70% by weight; the buffer is in an amount of from about 20% to about 30% by weight; and the polynucleotide stabiliser is in an amount of from about 2% to about 20% by weight. [0084] Each of the anionic surfactant, buffer and polynucleotide stabiliser may be selected as disclosed elsewhere herein. USES AND METHODS FOR INACTIVATION / PRESERVATION [0085] Formulations and mixtures of the invention may be used for the inactivation of a pathogen and/or preservation of pathogen polynucleotides. Accordingly, also disclosed are relevant uses and methods of using the formulations and mixtures. [0086] An embodiment provides use of an aqueous formulation of the invention for the inactivation of a pathogen. The use may comprise contacting the aqueous formulation with a sample comprising the pathogen. The contacting may be performed at any suitable temperature. For example, the contacting may be performed at a temperature of from about 2 °C to about 40 °C, for example at a temperature of from about 10 °C to about 30 °C, such as room temperature. The pathogen may release pathogen polynucleotides into the solution after contacting. The use may further comprise the preservation of pathogen polynucleotides, e.g. during storage or transport after said contacting. The polynucleotide may be RNA or DNA. The polynucleotide may be RNA. The polynucleotide may be DNA. The use may further comprise identifying the pathogen, e.g. by sequencing the pathogen polynucleotides. [0087] An embodiment provides use of an aqueous formulation of the first aspect for the preservation of pathogen polynucleotides. The polynucleotide may be RNA or DNA. The polynucleotide may be RNA. The polynucleotide may be DNA. The use may comprise contacting the aqueous formulation with the pathogen polynucleotides. The use may comprise maintaining the aqueous formulation (e.g. the aqueous formulation after said contacting) at a temperature of from about -80 °C to about 40 °C. Typically, the use may comprise maintaining the aqueous formulation (e.g. the aqueous formulation after said contacting) at a temperature of from about 2 °C to about 40 °C, for example at a temperature of from about 10 °C to about 30 °C, such as room temperature. The use may further comprise identifying the pathogen. [0088] An embodiment provides a method of inactivating a pathogen, the method comprising contacting a sample containing the pathogen with a formulation of the invention. The contacting may be performed at any suitable temperature. For example, the contacting may be performed at a temperature of from about 2 °C to about 40 °C, for example at a temperature of from about 10 °C to about 30 °C, such as room temperature. The pathogen may release pathogen polynucleotides into the solution after contacting. The polynucleotide may be RNA or DNA. The polynucleotide may be RNA. The polynucleotide may be DNA. The method may further comprise the preservation of pathogen polynucleotides, e.g. during storage or transport after said contacting. The method may further comprise analysis of the sample and identifying the pathogen. The method of analysis may comprise sequencing the pathogen polynucleotides. [0089] An embodiment provides a method of preserving pathogen polynucleotides, the method comprising contacting a sample containing the pathogen with a formulation of the first aspect to provide a contacted sample. The polynucleotide may be RNA or DNA. The polynucleotide may be RNA. The polynucleotide may be DNA. The method may comprise storing the contacted sample. The storing may comprise maintaining the aqueous formulation after said contacting at a temperature of from about -80 °C to about 40 °C. Typically, the storing comprises maintaining the aqueous formulation after said contacting at a temperature of from about 2 °C to about 40 °C, for example at a temperature of from about 10 °C to about 30 °C, such as room temperature. The method may further comprise analysis of the sample and identifying a pathogen, e.g. by sequencing the pathogen polynucleotides. [0090] An embodiment provides use of a solid mixture of the invention for the inactivation of a pathogen. The use may comprise contacting an aqueous sample containing the pathogen with the solid mixture. The contacting may be performed at any suitable temperature. For example, the contacting may be performed at a temperature of from about 2 °C to about 40 °C, for example at a temperature of from about 10 °C to about 30 °C, such as room temperature. The pathogen may release pathogen polynucleotides into the solution after contacting. The use may further comprise the preservation of pathogen polynucleotides, e.g. during storage or transport after said contacting. The polynucleotide may be RNA or DNA. The polynucleotide may be RNA. The polynucleotide may be DNA. The use may further comprise identifying the pathogen, e.g. by sequencing the pathogen polynucleotides. [0091] An embodiment provides a use of solid mixture of the invention for the preservation of pathogen polynucleotides. The use comprises contacting an aqueous sample containing the pathogen with the solid mixture. The polynucleotide may be RNA or DNA. The polynucleotide may be RNA. The polynucleotide may be DNA. The use may comprise contacting the aqueous formulation with the pathogen polynucleotides. The use may comprise maintaining the aqueous formulation (e.g. the aqueous formulation after said contacting) at a temperature of from about -80 °C to about 40 °C. Typically, the use may comprise maintaining the aqueous formulation (e.g. the aqueous formulation after said contacting) at a temperature of from about 2 °C to about 40 °C, for example at a temperature of from about 10 °C to about 30 °C, such as room temperature. The use may further comprise identifying a pathogen, e.g. by sequencing the pathogen polynucleotides. [0092] An embodiment provides a method of inactivating a pathogen, the method comprising contacting an aqueous sample containing the pathogen with a solid mixture of the invention. The contacting may be performed at any suitable temperature. For example, the contacting may be performed at a temperature of from about 2 °C to about 40 °C, for example at a temperature of from about 10 °C to about 30 °C, such as room temperature. The pathogen may release pathogen polynucleotides into the solution after contacting. The polynucleotide may be RNA or DNA. The polynucleotide may be RNA. The polynucleotide may be DNA. The method may further comprise the preservation of pathogen polynucleotides, e.g. during storage or transport after said contacting. The method may further comprise analysis of the sample and identifying the pathogen. The method of analysis may comprise sequencing the pathogen polynucleotides. [0093] An embodiment provides a method of preserving pathogen polynucleotides, the method comprising contacting an aqueous sample containing the pathogen with a solid mixture of the invention to provide a contacted sample. The polynucleotide may be RNA or DNA. The polynucleotide may be RNA. The polynucleotide may be DNA. The method may comprise storing the contacted sample. The storing may comprise maintaining the aqueous formulation after said contacting at a temperature of from about -80 °C to about 40 °C. Typically, the storing may comprise maintaining the aqueous formulation after said contacting at a temperature of from about 2 °C to about 40 °C, for example at a temperature of from about 10 °C to about 30 °C, such as room temperature. The method may further comprise analysis of the sample and identifying a pathogen, e.g. by sequencing the pathogen polynucleotides [0094] In the uses and methods described herein, the pathogen may be a virus, a bacterium, a fungus, or a parasite. [0095] The pathogen may be selected from coronaviruses, rotaviruses, noroviruses, enteroviruses, hepatitis viruses, herpesviruses, papillomaviruses, arboviruses (e.g. West Nile virus, Zika virus, Dengue virus), ebolaviruses, orthomyxoviruses, paramyxoviruses, rabies virus, parechovirus, rubella virus., Escherichia coli, Staphylococcus aureus, Chlamydia trachomatis, Mycoplasma spp, Bordatella pertussis, Bordatella parapertussis, Streptococcus pyogenes, Streptococcus agalactiae, Candida spp (e.g. Candida auris), Trichomonas vaginalis, Listeria monocytogenes, Bacillus anthracis, Yersinia pestis, Francisella spp, Neisseria gonorrhoea, Neisseria meningitidis, Salmonella spp, Shigella spp, Campylobacter spp, Fusobacterium necrophorum, Mycobacterium spp, Legionella pneumophila, Giardia duodenalis, Cryptosporidium spp, Helicobacter pylori, and Treponema pallidum. [0096] In the uses and methods described herein, the pathogen may be a virus or a bacterium. [0097] The pathogen may be selected from coronaviruses, rotaviruses, noroviruses, enteroviruses, hepatitis viruses, herpesviruses, papillomaviruses, arboviruses (e.g. West Nile virus, Zika virus, Dengue virus), ebolaviruses, orthomyxoviruses, paramyxoviruses, rabies virus, parechovirus, rubella virus., Escherichia coli, Staphylococcus aureus, Chlamydia trachomatis, Mycoplasma spp, Bordatella pertussis, Bordatella parapertussis, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Bacillus anthracis, Yersinia pestis, Francisella spp, Neisseria gonorrhoea, Neisseria meningitidis, Salmonella spp, Shigella spp, Campylobacter spp, Fusobacterium necrophorum, Mycobacterium spp, Legionella pneumophila, Giardia duodenalis, Helicobacter pylori, and Treponema pallidum. [0098] The pathogen may be a virus, e.g. an enveloped or non-enveloped virus. The enveloped or non-enveloped virus may be selected from: coronaviruses, rotaviruses, noroviruses, enteroviruses, hepatitis viruses, herpesviruses, papillomaviruses, arboviruses (e.g. West Nile virus, Zika virus, Dengue virus), ebolaviruses, orthomyxoviruses, paramyxoviruses, rabies virus, parechovirus, or rubella virus. [0099] The pathogen may be an enveloped virus (e.g. an enveloped RNA virus, such as the coronavirus illustrated in Figure 1). The enveloped virus may be an influenza virus (e.g. IAV, IBV, ICV, IDV). The enveloped virus may be a coronavirus. [00100] The pathogen may be a coronavirus. The pathogen may be selected from severe acute respiratory syndrome coronavirus (SARS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus OC43 (HCoV-OC43), human coronavirus HKU1 (HCoV- HKU1), human coronavirus 229E (HCoV-229E), and human coronavirus NL63 (HCoV- NL63), or any variants thereof. The pathogen may be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or a variant thereof. [00101] The pathogen may be a bacterium. The bacterium may be a Clostridium, a Pseudomonas, an Escherichia, a Klebsiella, an Enterococcus, an Enterobacter, a Serratia, a Stenotrophomonas, an Aeromonas, a Morganella, a Yersinia, a Salmonella, a Proteus, a Pasteurella, a Haemophilus, a Citrobacter, a Burkholderia, a Brucella, a Moraxella, a Mycobacterium, a Streptococcus, a Chlamydia, a Mycoplasma, a Bordatella, a Listeria, a Bacillus, a Francisella, a Neisseria, a Shigella, a Campylobacter, a Fusobacterium, a Legionella, a Helicobacter, a Streptococcus, or a Staphylococcus. The bacterium may be an Escherichia (e.g. Escherichia coli) or a Staphylococcus (e.g. a Staphylococcus aureus). [00102] The pathogen may be a fungus. The fungus may be a Blastomyces, a Coccidioides, a Paracoccidioides, a Histoplasma, a Cryptococcus, a Trichophyton, a Microsporum, a Mucor, an Aspergillus, a Sporothrix, or a Talaromyces. METHODS OF IDENTIFYING A PATHOGEN [00103] An embodiment provides a method of identifying a pathogen, comprising contacting a sample containing a suspected pathogen with an aqueous formulation of the invention to provide a sample solution comprising suspected pathogen polynucleotides; optionally storing and/or transporting the sample solution; separating the suspected pathogen polynucleotides from the solution; and subjecting the suspected pathogen polynucleotides to a detection process; and identifying said suspected pathogen, if present, based on the detected pathogen polynucleotides. [00104] Another embodiment provides a method of identifying a pathogen, comprising contacting an aqueous sample containing a suspected pathogen with a solid mixture of the invention to provide a sample solution comprising suspected pathogen polynucleotides; optionally storing and/or transporting the sample solution; separating the suspected pathogen polynucleotides from the solution; and subjecting the suspected pathogen polynucleotides to a detection process; and identifying said suspected pathogen, if present, based on the detected pathogen polynucleotides. [00105] The detection process may comprise polymerase chain reaction (PCR) amplification. For example, the detection process may comprise quantitative polymerase chain reaction (qPCR). Where the pathogen polynucleotides are RNA, the detection process may comprise reverse-transcription polymerase chain reaction (e.g. using reverse transcriptase, to create complementary DNA (cDNA) copies of the RNA, then performing qPCR with that cDNA). KITS [00106] Formulations and mixtures of the disclosure are useful in the inactivation of pathogens and/or stabilisation of pathogen nucleic acids. Accordingly, the formulations and mixtures of the invention may be provided in containers suitable for use with individual or pooled samples comprising (suspected) pathogen. Such containers may then be used for the inactivation of pathogens and/or stabilisation of pathogen nucleic acids prior to analysis of the samples for detection of the (suspected) pathogen. [00107] An embodiment provides a kit comprising a container comprising an aqueous formulation of the invention or a solid mixture of the invention. [00108] The kit may also comprise a sampling apparatus. The sampling apparatus may comprise a swab and/or funnel. [00109] The container may be configured such that, after sampling, the container comprises the sample in addition to the aqueous formulation or solid mixture. The container may be sealable after sampling. [00110] The container may have a volume of less than about 50 mL, less than about 40 mL, less than about 30 mL, less than about 20 mL, less than about 10 mL, or less than about 5 mL. The container may have a volume of at least about 0.1 mL, at least about 0.5 mL, or at least about 1 mL. The container may have a volume of from about 0.1 mL to about 50 mL. The container may have a volume of from about 0.5 mL to about 20 mL. The container may have a volume of from about 1 mL to about 10 mL. [00111] While the aqueous solution and (when dissolved in the container) solid mixture are believed to be self-sterilising, the container and (if present) any sampling apparatus may be provided sterile. Providing components of the kit in sterile form prior to sampling reduces the risk of pre-contamination of the kit with pathogen prior to sampling. [00112] The kit may comprise instructions. [00113] The kit may further comprise may further comprise at least one label. The label may comprise an ID to assist tracking of the container after sampling. The kit may further comprise packaging, wherein the container and optionally other kit components are provided within the packaging. EXAMPLES Example 1: Formulations and Testing [00114] The following components were mixed together in the given amounts to provide a formulation of the invention: [00115] The inactivation of four bacteriophages (enveloped T2, M13, Phi-X174 and non- enveloped Phi-6) and two bacteria (Escherichia coli and Staphylococcus aureus) were tested using formulations containing sodium dodecyl sulfate and different buffers (including sodium citrate / citric acid, lactic acid / sodium lactate, glycine – hydrochloric acid and sodium acetate / acetic acid) at different pH values. The pH values tested were from about 3.5 to about 4. The sodium dodecyl sulfate concentration was reduced from 1% to 0.95% to be less hazardous. The formulations were tested at full-strength and also 75% strength. The table below shows the number of viral plaques (PFU/mL) or bacterial colonies (CFU/mL) present following treatment with each formulation. [00116] Table 1: Results for exemplary formulations

[00117] Complete inactivation of all phages and bacteria was achieved using the full- strength formulations. At 75% strength, the formulations containing glycine, acetate and lactate buffers at pH 3.5 gave complete inactivation. Thus, low pH contributes further to inactivation. Without wishing to be bound by any theory, it is believed that the improved inactivation at low pH (compared to higher pH) is due to the low pH having an activating effect on sodium dodecyl sulfate and similar anionic surfactants. Example 2: Manufacture of formulations [00118] The following components were mixed together in the given amounts to provide a formulation of the invention: Sodium dodecyl sulfate (CAS 151-21-3) = 0.75% w/v (26 mM) Sodium lactate (CAS 867-56-1) = 0.051% w/v (10 mM) Lactic acid (CAS 79-33-4) = 0.216% w/v Sodium citrate (CAS 6132-04-3) = 0.06% w/v (2 mM) [00119] The pH value was measured at 3.5. The formulation was dispensed into 2 mL volumes and was stored at room temperature (10-30°C). Example 3: Morphology of SARS-CoV-2 [00120] SARS-CoV-2 has a structure as illustrated in Figure 1, which includes a lipid envelope (E) 10 and three structural proteins: spike glycoprotein (S) 20, membrane protein (M) 30, and nucleocapsid (N) 40; as well as RNA 50 and hemagglutinin esterase-dimer (HE) 60. The overall virus is approximately 100 nm in size. Viral entry into host cells is mediated by spike glycoprotein 20. [00121] Sodium dodecyl sulfate (SDS) disrupts the lipid envelope (E) 10, and binds to both membrane and non-membrane proteins. SDS binding is also cooperative so binding of one monomer encourages the binding of more. Detergent monomers then solubilize the membrane proteins by partitioning into the membrane bilayer. See Figure 2. [00122] SDS’s sulphate region disrupts non-covalent bonds and the hydrocarbon tail dissolves hydrophobic regions in the structural proteins causing them to lose their conformational shape and function. The formulation is also at a low pH (3.5) and acid- induced protein unfolding of effected salt bridges and hydrogen bonds typically occurs at pH values < 5. S protein alteration by denaturation in an SDS / low pH environment renders the virus unable to bind to host cells. [00123] SDS at low pH (below pH 4) is shown to reduce the critical micellar concentration (CMC), which encourages micelles to form at a lower concentration than normal. Micelles are more stable the further they are away from their CMC. Hydrogen ions may decrease electrostatic repulsion of the charged SDS heads by decreasing the charge density on the surface of the micelle, changing the micelle’s stability. This means complexes formed in Figure 2 are likely to be formed and then stabilise over time. The SDS / low pH combination also denatures the three other structural proteins E, M and N. Additionally, the SDS dissolves the lipid envelope that encapsulates the genetic material, thereby resulting in inactivation of the virus. [00124] Viral RNA is preserved in the formulation by a combination of lower pH and sodium citrate. Without wishing to be bound by theory, it is thought that the sodium ions create a temporary attraction between sodium and the phosphate backbone of RNA. RNA is most stable around pH 4. The RNA is temporarily neutralized and sodium citrate in solution also acts as a strong chelating agent, thereby preventing oxidation and inactivating metal ion-dependent nucleases which would otherwise degrade the target RNA. Example 4: Inactivation of SARS-CoV-2 [00125] A high titre stock of the SARS-CoV-2 strain England/2/2020 was spiked into the formulation of Example 2. The stock of virus has a titre of 2.5 x 10⁷ pfu/mL. A viral plaque assay was then conducted on Vero E6 cells, along with a triple passaging assay on Vero V1 cells. No virus was detected in either assay. Example 5: SARS-CoV-2 RNA stability study [00126] Tubes containing the formulation of Example 2 were spiked with a high titre stock of the SARS-CoV-2 strain England/2/2020. The tubes were then stored for five days at room temperature followed by five days in the refrigerator. PCR was conducted throughout to determine stability of viral RNA in the medium. Over the 10-day storage period, there was no significant difference in cycle threshold value for N gene, S gene or ORF1a gene (all values were within 1 CT of time 0), thus indicating no significant degradation of RNA over time. Example 6: Human RNA stability study [00127] Three tubes were prepared containing the formulation of Example 2. The tubes were spiked with 8 µL of total human RNA that had been previously diluted 1:10 with purified water. The tubes were run through extraction using the MagMAX VP NAI II Kit on a KingFisher Flex system. The elution from each extraction was run once each on real- time PCR using the TaqPATH master mix and ACTB TaqMan primers and probes. The tubes of the formulation + RNA were then moved to a 30°C incubator. The tubes were sampled again at 3 days. At this time 250 µL aliquots were refrigerated at 4°C. The sample tubes were replaced in the 30°C incubator and sampled again at the 5 day timepoint before being moved into the refrigerator. The aliquots taken previously were sampled after 3 days in the refrigerator, and the sample tubes were sampled after 6 days in the refrigerator. [00128] Table 2: Results from RNA stability study (a) Time 0 RNA Stability

(b) 3 days at 30°C RNA Stability

(c) 5 days at 30°C RNA Stability

(d) 3 days at 30°C + 3 days at 2-8°C RNA Stability

(e) 5 days at 30°C + 5 days at 2-8°C RNA Stability

[00129] At all timepoints (a) to (e) the formulation showed <1 CT difference when compared to Time 0, indicating no significant degradation of RNA over time.

Claims

CLAIMS 1. An aqueous formulation for inactivating a pathogen, the aqueous formulation comprising: an anionic surfactant in a concentration of from about 15 mM to about 70 mM; a polynucleotide stabiliser in a concentration of from about 1 mM to about 200 mM; and a buffer providing a pH of from about 2 to about 4.2.

2. The aqueous formulation of any preceding claim, wherein the anionic surfactant is present in a concentration of from about 20 mM to about 30 mM.

3. The aqueous formulation of any preceding claim, wherein the anionic surfactant is present in a concentration of about 26 mM.

4. The aqueous formulation of any preceding claim, wherein the anionic surfactant is selected from alkyl sulfates, alkyl ether sulfates, arylalkyl sulfates, alkyl aryl ether sulfates alkyl ester sulfates, alkyl sulfonates, alkyl ether sulfonates, arylalkyl sulfonates, alkyl aryl ether sulfonates, alkyl ester sulfonates, alkyl α-olefin sulfonates, alkyl phosphates, alkyl ether phosphates, arylalkyl phosphates, alkyl aryl ether phosphates, alkyl ester phosphates, alkyl carboxylates, alkylamido carboxylates, alkyl ether carboxylates, arylalkyl carboxylates, alkyl aryl ether carboxylates, and alkyl ester carboxylates.

5. The aqueous formulation of any preceding claim, wherein the anionic surfactant is a C4-24 alkyl sulfate, optionally wherein the anionic surfactant is a C8-18 alkyl sulfate.

6. The aqueous formulation of any preceding claim, wherein the anionic surfactant is selected from: sodium dodecyl sulfate, sodium octyl sulfate, sodium 2-butyloctyl sulfate, sodium 2-ethylhexyl sulfate, sodium 3,7-dimethyloctyl sulfate, sodium lauryl sulfate, sodium lauryl sarcosinate, ammonium lauryl sulfate, sodium laureth sulfate, ammonium laureth sulfate, sodium myreth sulfate, sodium pareth sulfate, C14-16 alkyl α-olefin sulfonate, sodium dodecylbenzene sulfonate, sodium octanesulfonate, sodium decanesulfonate, sodium nonanesulfonate, sodium heptanesulfonate, sodium hexanesulfonate, sodium pentanesulfonate, sodium butanesulfonate, sodium stearate, dioctyl sodium sulfosuccinate.

7. The aqueous formulation of any preceding claim, wherein the anionic surfactant is sodium dodecyl sulfate.

8. The aqueous formulation of any preceding claim, wherein the formulation has a pH of at least about 3, optionally a pH of at least about 3.3.

9. The aqueous formulation of any preceding claim, wherein the formulation has a pH of from about 3 to about 4.

10. The aqueous formulation of any preceding claim, wherein the formulation has a pH of about 3.5.

11. The aqueous formulation of any preceding claim, wherein the buffer in a concentration of from about 1 mM to about 500 mM; optionally wherein the buffer is at a concentration of from about 5 mM to about 150 mM, optionally wherein the buffer is at a concentration of from about 5 to about 100 mM, further optionally wherein the buffer is at a concentration of about 10 mM.

12. The aqueous formulation of any preceding claim, wherein the buffer comprises or is selected from: lactate/lactic acid, glycine – hydrochloric acid and acetate/acetic acid.

13. The aqueous formulation of any preceding claim, wherein the buffer system comprises or is lactate/lactic acid, optionally wherein the lactate is sodium lactate.

14. The aqueous formulation of any preceding claim, wherein the polynucleotide stabiliser is citrate in a concentration of from about 1 mM to about 150 mM.

15. The aqueous formulation of claim 14, wherein the citrate is present in an amount of about 1 to about 3 mM; optionally wherein the citrate is present in an amount of about 1.2 mM to about 2.8 mM, further optionally wherein the citrate is present in an amount of about 1.5 mM to about 2.5 mM.

16. The aqueous formulation of any preceding claim, wherein the citrate is present in an amount of about 2 mM.

17. The aqueous formulation of any preceding claim, wherein the citrate is sodium citrate.

18. The aqueous formulation of any preceding claim, wherein the aqueous formulation is non-hazardous.

19. Use of an aqueous formulation of any preceding claim for the inactivation of a pathogen, optionally wherein the use further comprises the preservation of pathogen polynucleotides.

20. Use of the formulation of any of claims 1 to 18 for the preservation of pathogen polynucleotides, optionally wherein the polynucleotide is RNA or DNA.

21. The use of claim 19 or claim 20, wherein the pathogen is a virus or a bacterium.

22. The use of any of claims 19 to 21, wherein the pathogen is an enveloped or non- enveloped virus.

23. The use of claim 22, wherein the enveloped or non-enveloped virus is selected from: coronaviruses, rotaviruses, noroviruses, enteroviruses, hepatitis viruses, herpesviruses, papillomaviruses, arboviruses (e.g. West Nile virus, Zika virus, Dengue virus), ebolaviruses, orthomyxoviruses, paramyxoviruses, rabies virus, parechovirus, or rubella virus.

24. The use of claim 22 or claim 23, wherein the enveloped virus is a coronavirus.

25. The use of any of claims 19 to 24, wherein the pathogen is selected from: severe acute respiratory syndrome coronavirus (SARS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus OC43 (HCoV-OC43), human coronavirus HKU1 (HCoV-HKU1), human coronavirus 229E (HCoV-229E), and human coronavirus NL63 (HCoV-NL63).

26. The use of any of claims 19 to 21, wherein the pathogen is a bacterium; optionally wherein the bacterium is selected from a Clostridium, a Pseudomonas, an Escherichia, a Klebsiella, an Enterococcus, an Enterobacter, a Serratia, a Stenotrophomonas, an Aeromonas, a Morganella, a Yersinia, a Salmonella, a Proteus, a Pasteurella, a Haemophilus, a Citrobacter, a Burkholderia, a Brucella, a Moraxella, a Mycobacterium, a Streptococcus, a Chlamydia, a Mycoplasma, a Bordatella, a Listeria, a Bacillus, a Francisella, a Neisseria, a Shigella, a Campylobacter, a Fusobacterium, a Legionella, a Helicobacter, a Streptococcus, or a Staphylococcus.

27. A method of inactivating a pathogen, the method comprising contacting a sample containing the pathogen with a formulation of any of claims 1 to 18.

28. A solid mixture comprising: an anionic surfactant in an amount of from about 50% to about 70% by weight; a buffer in an amount of from about 20% to about 30% by weight; and a polynucleotide stabiliser in an amount of from about 2% to about 20% by weight.

29. The solid mixture of claim 28, wherein the anionic surfactant is in an amount of about 70% by weight.

30. The solid mixture of claim 28 or claim 29, wherein the buffer is in an amount of about 25% by weight.

31. The solid mixture of any of claims 28 to 30, wherein the buffer is formulated to provide a pH of from about 2 to about 4.2 when the solid mixture is solubilised in water to provide an aqueous solution with the buffer at a concentration of from about 25 mM to about 150 mM.

32. The solid mixture of any of claims 28 to 31, wherein the polynucleotide stabiliser is citrate in an amount of from about 2% to about 10% by weight; optionally wherein the citrate is in an amount of about 5% by weight.

33. A method of identifying a pathogen, comprising: contacting a sample containing a suspected pathogen with an aqueous formulation of any of claims 1 to 18 to provide a sample solution comprising suspected pathogen nucleic acid; storing and/or transporting the sample solution; separating the suspected pathogen polynucleotides from the solution; and subjecting the suspected pathogen polynucleotides to a detection process, and identifying said suspected pathogen, if present, based on the detected pathogen polynucleotides.

34. A kit comprising: a container comprising an aqueous formulation of any of claims 1 to 18 or a solid mixture of any of claims 28 to 32; and optionally a sterile swab and/or funnel.