EP1996023A1 - Method for disabling viruses - Google Patents
Method for disabling virusesInfo
- Publication number
- EP1996023A1 EP1996023A1 EP07705278A EP07705278A EP1996023A1 EP 1996023 A1 EP1996023 A1 EP 1996023A1 EP 07705278 A EP07705278 A EP 07705278A EP 07705278 A EP07705278 A EP 07705278A EP 1996023 A1 EP1996023 A1 EP 1996023A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- virus
- environment
- haemagglutinin
- exposing
- air
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 241000700605 Viruses Species 0.000 title claims abstract description 69
- 238000000034 method Methods 0.000 title claims abstract description 28
- 241000712461 unidentified influenza virus Species 0.000 claims abstract description 27
- 230000008859 change Effects 0.000 claims abstract description 16
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 9
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 8
- 230000010076 replication Effects 0.000 claims abstract description 8
- 230000014599 transmission of virus Effects 0.000 claims abstract description 6
- 230000002378 acidificating effect Effects 0.000 claims abstract 4
- 239000002245 particle Substances 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 230000003612 virological effect Effects 0.000 claims 4
- 230000005540 biological transmission Effects 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 24
- 208000015181 infectious disease Diseases 0.000 description 13
- 230000008569 process Effects 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 230000000415 inactivating effect Effects 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 210000001163 endosome Anatomy 0.000 description 6
- 206010022000 influenza Diseases 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000002458 infectious effect Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 102000005348 Neuraminidase Human genes 0.000 description 4
- 108010006232 Neuraminidase Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical class C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 238000004378 air conditioning Methods 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 230000035931 haemagglutination Effects 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- 230000029812 viral genome replication Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 235000005979 Citrus limon Nutrition 0.000 description 2
- 244000131522 Citrus pyriformis Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 229960003260 chlorhexidine Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000052 vinegar Substances 0.000 description 2
- 235000021419 vinegar Nutrition 0.000 description 2
- 210000000605 viral structure Anatomy 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 244000186140 Asperula odorata Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 235000008526 Galium odoratum Nutrition 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 229940124873 Influenza virus vaccine Drugs 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 1
- 229910001573 adamantine Inorganic materials 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000010796 biological waste Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 210000003837 chick embryo Anatomy 0.000 description 1
- -1 chlorhexidine citrate salt Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003398 denaturant Substances 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 229940124590 live attenuated vaccine Drugs 0.000 description 1
- 229940023012 live-attenuated vaccine Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002906 medical waste Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920005749 polyurethane resin Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229940061374 relenza Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000012876 topography Methods 0.000 description 1
- 230000000725 urealytic effect Effects 0.000 description 1
- 230000007501 viral attachment Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- ARAIBEBZBOPLMB-UFGQHTETSA-N zanamivir Chemical compound CC(=O)N[C@@H]1[C@@H](N=C(N)N)C=C(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO ARAIBEBZBOPLMB-UFGQHTETSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/02—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L9/00—Disinfection, sterilisation or deodorisation of air
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N65/00—Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
- A01N65/08—Magnoliopsida [dicotyledons]
- A01N65/36—Rutaceae [Rue family], e.g. lime, orange, lemon, corktree or pricklyash
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F24—HEATING; RANGES; VENTILATING
- F24F—AIR-CONDITIONING; AIR-HUMIDIFICATION; VENTILATION; USE OF AIR CURRENTS FOR SCREENING
- F24F3/00—Air-conditioning systems in which conditioned primary air is supplied from one or more central stations to distributing units in the rooms or spaces where it may receive secondary treatment; Apparatus specially designed for such systems
- F24F3/12—Air-conditioning systems in which conditioned primary air is supplied from one or more central stations to distributing units in the rooms or spaces where it may receive secondary treatment; Apparatus specially designed for such systems characterised by the treatment of the air otherwise than by heating and cooling
- F24F3/16—Air-conditioning systems in which conditioned primary air is supplied from one or more central stations to distributing units in the rooms or spaces where it may receive secondary treatment; Apparatus specially designed for such systems characterised by the treatment of the air otherwise than by heating and cooling by purification, e.g. by filtering; by sterilisation; by ozonisation
Definitions
- the present invention relates to a method for disabling viruses and is particularly although not exclusively applicable to the disabling of the influenza virus.
- influenza virus vaccine is the scientifically accepted method for the prevention of an influenza virus infection.
- vaccines both live attenuated vaccines and killed vaccines, obtained by the use of formalin and beta-propriolactone with or without subsequent virus component fractionation and purification, is equally known and has been exploited over the last forty years.
- Pharmaceuticals such as, in the case of influenza, Adamantine, Tamifiu® and Relenza® have weaknesses too, either because of side-effects, or because it has already been shown that influenza virus (H5N1) is becoming resistant. Other pharmaceuticals are now being urgently sought.
- influenza viruses When a cell is infected with influenza, whatever the strain, the infected cell, goes through the same biological processes. These processes include the steps of virus adsorption, virus penetration, virus nucleic acid release and virus nucleic acid and protein replication, using the replication mechanisms of the infected cell.
- the particles replicated include, of course, the virus's haemagglutinin and the enzyme for virus particle release named the neuraminidase.
- influenza viruses are now classified according to their haemagglutinin (H) and their neuraminidase (N), for example H5N1, or H2N2.
- JP-2002-058730 discloses an influenza virus prehension filter which can be used with air filters to prevent infection with an influenza virus.
- examples include mask filters, filters for air cleaners and filters for air-conditioners. These filters are specifically synthesized to chemically mimic the receptor to which the haemagglutinin of influenza virus attaches, such that virus particles adhere to the filter rather than pass though.
- a filter such as this is complex to manufacture, and therefore is expensive.
- EP 1 510 130 Al is concerned with a virus inactivating agent and virus inactivating method, and a filter set having the inactivating agent, and an air conditioner equipped with the filter set.
- the product requires heavy engineering and will not function easily as a personal filter and virus inactivation system.
- the claims cover using a protein denaturant, preferably urea, and proteolytic enzyme acting together to destroy the captured virus particles and other micro organisms. It would be astonishing if individuals agreed to spray urea on themselves together with or without the protease enzyme.
- the virus destroying system is activated after virus capture.
- the air conditioner is impractical because it needs to maintain the inside space "hot and humid".
- the air suitable for the activation of the virus inactivating agent is agitated by an air blower in the hermetically sealed space.
- the air conditioner used must therefore be both an air blower and an air conditioner (equipped with virus filter and means of activating the same by heating and cooling).
- the filter traps the virus prior to the activation of the virus inactivating system. Heat and / or pressure have been used for many years to destroy micro organisms.
- JP 10 145505 discloses a process of virus inactivation using chlorhexidine salts, or an inorganic acid, in a filter.
- the virus inactivating process disclosed is slow and cumbersome providing 90% inactivation in 24 hours.
- the virus destroying solution discloses use of citric acid but only in the context of forming the chlorhexidine citrate salt. Equally the other chlorhexidine salts formed are the acetate, the chloride, and the phosphate.
- the preferential composition for the inactivating agent for influenza virus is chlorhexidine glyconate (40% solution in water) 40% polyurethane resin, 5% water and 15% non-ionic system surfactant.
- the present invention utilises a step in the virus multiplication process, namely the change in shape of the virus haemagglutinin with pH less than 6 to change haemagglutinin shape and prevent the virus from binding to cells.
- the present invention provides a method of inhibiting viral transmission characterised by exposing virus to an environment causing virus particle replication steps to occur out of sequence.
- the invention provides a method for inhibiting viral transmission characterised by exposing the virus to an environment which causes a topographical change, thus preventing adhesion of the virus to the host cell.
- the environment may be an environment having a pH ⁇ 6, and in particular may have a pH in the range 4-6.
- Influenza virus replication may be explained as a series of steps, such as, for example :-
- Virus assembly including haemagglutinin and neuraminidase migration to the surface of the infected cell at pH greater than or equal to pH 6 — 7.
- the present invention moves step 4 to precede step 1 and thus prevents the binding of the virus to the host cell so the replication cycle of the virus is not initiated.
- influenza virus causes red blood cells to aggregate.
- the antigen concerned is haemagglutinin.
- Haemagglutinin has been shown to occur on the surface of viruses and to be responsible for the adsorption of the virus particle onto a red blood cell and onto cells that can be infected.
- Haemagglutinin activity is quantitative and enables the numbers of virus particles to be estimated. In a given suspension of infectious virus particles the haemagglutinin activity is proportional to its infectivity. Genetic changes in this haemagglutinin antigen are largely responsible for the virus maintaining its infectivity in face of the host's antibody response.
- the inventor's experiments show that the ability to detect haemagglutinin disappears as the pH of the allantoic fluid containing influenza virus is reduced. This in turn indicates that a reduced pH will leave virus particles with a reduced or no capacity to bind to host cells and hence disable infectivity.
- the present invention advances the normal infectious process that occurs within the virus-containing endosomes of infected cells by making the step mediated by lower than normal pH in the endosomes of the infectious cycle occur prior to cell attachment.
- the step change makes influenza virus haemagglutinin unable to attach the potentially infecting virus particle to cells.
- the change in shape of influenza virus haemagglutinin by lowered pH is a general phenomenon with all types of influenza virus and this topographical change in the haemagglutinin stops adsorption (infection) occurring.
- the haemagglutinin is not destroyed or denatured; the haemagglutinin's topography is merely changed.
- the process of bringing forward the process of topographical haemagglutinin change differentiates this process from the other methods used to control infections with products that denature, disintegrate, pasteurize, disinfect, and otherwise demolish and destroy virus proteins, virus lipoproteins (membranes) and virus nucleoproteins.
- the present invention transposes a natural change by bringing it forward to occur earlier and before cell infection.
- influenza virus particles can be effectively disabled.
- An apparatus used for this can be a personal device (or a group device or air conditioner). It may or may not include returning the pH to neutral (pH 7) before the air is inhaled.
- the process might be used with and / or without masks and other air-conditioning equipment. The process could be used in crowded places on land, sea or air.
- the applications are air handling systems, including but not limited to air-conditioning units in buildings, air-circulation systems in aircraft and air filtration systems. Alternatively in suitable environments it may be possible merely to spray the diluted mild acid (for example, at pH 4 — pH 6) into the air of closed rooms or poultry houses or pig-sties to assist the more normal (ruthless) disinfection regimes.
- the mild acids include but are not limited to vinegar (acetic acid) and its salts (e.g. sodium acetate) or other acidic compounds such as lemon juice (citric acid and its salts).
- the agents of change are easily accessible, low in cost and in common usage.
- the apparatus used can be simple or refined, personal or air-conditioners.
- inventions include suitably treated nose and mouth masks and / or use devices such as eastern water-cooled smoking devices and / or nasal sprays.
- a further embodiment of the invention could be used in air-conditioners, air-cleaners, humidifiers and driers.
- This embodiment could be applied to medical wastes, biological wastes, seats and cushions, walls and curtains, floors and floor coverings, including but not limited to carpets and mats.
- Masks and clothes for medical workers could be sprayed.
- Ambulances and stretchers could also be treated either routinely or when they have carried infected patients.
- Haemagglutinin is the influenza antigen responsible for virus attachment to cells. It allows influenza virus to adhere to cells which is the first part of the infection process.
- the following experimental results show the instability of influenza virus haemagglutinin to pH changes.
- the strains used were A/Eng/12/64, A/Eng/76/66, B/Eng/939/59 and B/Eng/5/66.
- the haemagglutinin (HA) detectable in virus containing fluids was significantly or totally reduced below pH 6.0 to 6.5.
- A/Eng/12/64 all the haemagglutinin activity had disappeared at pH 4.0 and below and more than 50% disappeared at pH 5.0.
- A/Eng/76/66 all the haemagglutinin activity had disappeared at pH 5.0 and below and more than 50% at pH 6.25.
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Environmental Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Dentistry (AREA)
- Plant Pathology (AREA)
- Agronomy & Crop Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Engineering & Computer Science (AREA)
- Combustion & Propulsion (AREA)
- Animal Behavior & Ethology (AREA)
- Mechanical Engineering (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Botany (AREA)
- Pest Control & Pesticides (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Viral transmission is inhibited by exposing the virus to an environment causing replication steps to occur out of their normal sequence. The virus may be exposed to an environment which causes a topological change to its exposed proteins (such as haemagglutinin), thus preventing adhesion of the virus to its host cell. The environment may be acidic, for example comprising a pH below 6, preferably between 4 and 6. The method may be used to inhibit transmission of the influenza virus.
Description
METHOD FOR DISABLING VIRUSES
The present invention relates to a method for disabling viruses and is particularly although not exclusively applicable to the disabling of the influenza virus.
Background to the invention
It is well known that a specific influenza virus vaccine is the scientifically accepted method for the prevention of an influenza virus infection.
The use of vaccines, both live attenuated vaccines and killed vaccines, obtained by the use of formalin and beta-propriolactone with or without subsequent virus component fractionation and purification, is equally known and has been exploited over the last forty years. Pharmaceuticals such as, in the case of influenza, Adamantine, Tamifiu® and Relenza® have weaknesses too, either because of side-effects, or because it has already been shown that influenza virus (H5N1) is becoming resistant. Other pharmaceuticals are now being urgently sought.
When a cell is infected with influenza, whatever the strain, the infected cell, goes through the same biological processes. These processes include the steps of virus adsorption, virus penetration, virus nucleic acid release and virus nucleic acid and protein replication, using the replication mechanisms of the infected cell. The particles replicated include, of course, the virus's haemagglutinin and the enzyme for virus particle release named the neuraminidase. Indeed influenza viruses are now classified according to their haemagglutinin (H) and their neuraminidase (N), for example H5N1, or H2N2.
The growth of viruses in the chick embryo was introduced by Woodruff and Goodpasture (1931) Am J Path 7, 209 - 222. Haemagglutination with influenza virus was first observed by George Hirst [Hirst, GK (1941) Science 94, 22-23]. He continued over many years to establish most of the basic concepts still used today with influenza virus. The eminent scientist SE Luria of the University of Illinois reviewed the concepts in his
book "General Virology" Published by Wiley (1953) in his "Summary on Virus Replication - Haemagglutination Phenomena and Virus Growth". This includes a description of the doubling dilution Haemagglutination Test pattern test used herein. - SaIk, J.E. (1944) J Immunol 49 87 - 98.
Methods for removing virus particles from the air we breathe have been extensively investigated, and include filtering, immobilisation and destruction of virus particles.
The use of filters on air-conditioning equipment and personal masks is well known and exploited commercially. Amongst other protective equipment these precautionary steps are well known and universally scientifically accepted. Also accepted is the use of detergents, disinfectants, surfactants and extreme acidity and alkalinity to destroy infectious agents whatever they may be, including but not limited to, moulds, bacteria, and viruses.
JP-2002-058730 discloses an influenza virus prehension filter which can be used with air filters to prevent infection with an influenza virus. Examples include mask filters, filters for air cleaners and filters for air-conditioners. These filters are specifically synthesized to chemically mimic the receptor to which the haemagglutinin of influenza virus attaches, such that virus particles adhere to the filter rather than pass though. A filter such as this is complex to manufacture, and therefore is expensive.
EP 1 510 130 Al is concerned with a virus inactivating agent and virus inactivating method, and a filter set having the inactivating agent, and an air conditioner equipped with the filter set. The product requires heavy engineering and will not function easily as a personal filter and virus inactivation system. The claims cover using a protein denaturant, preferably urea, and proteolytic enzyme acting together to destroy the captured virus particles and other micro organisms. It would be astonishing if individuals agreed to spray urea on themselves together with or without the protease enzyme. The virus destroying system is activated after virus capture. The air conditioner is impractical because it needs to maintain the inside space "hot and humid". "Preferably" those
authors state that the air suitable for the activation of the virus inactivating agent is agitated by an air blower in the hermetically sealed space. The air conditioner used must therefore be both an air blower and an air conditioner (equipped with virus filter and means of activating the same by heating and cooling). The filter traps the virus prior to the activation of the virus inactivating system. Heat and / or pressure have been used for many years to destroy micro organisms.
JP 10 145505 discloses a process of virus inactivation using chlorhexidine salts, or an inorganic acid, in a filter. The virus inactivating process disclosed is slow and cumbersome providing 90% inactivation in 24 hours. The virus destroying solution discloses use of citric acid but only in the context of forming the chlorhexidine citrate salt. Equally the other chlorhexidine salts formed are the acetate, the chloride, and the phosphate. However the preferential composition for the inactivating agent for influenza virus is chlorhexidine glyconate (40% solution in water) 40% polyurethane resin, 5% water and 15% non-ionic system surfactant.
What has not been exploited is the general "weakness" in virus replication. For example, it is known that there are many strains of common cold virus. However the infected cell, and the whole body, does not have a corresponding multiplicity of ways to react to infection. This results in similar if not identical symptoms being shown upon infection by a number of virus strains. In the case of influenza virus there are several points of weakness in common. The current invention exploits a common step and may make it possible, in times of an actual epidemic when vaccine supplies are inadequate or their distribution is poor, to radically reduce influenza and other virus transmission.
The present invention utilises a step in the virus multiplication process, namely the change in shape of the virus haemagglutinin with pH less than 6 to change haemagglutinin shape and prevent the virus from binding to cells.
Description of the Invention
The present invention provides a method of inhibiting viral transmission characterised by exposing virus to an environment causing virus particle replication steps to occur out of sequence. In a further embodiment the invention provides a method for inhibiting viral transmission characterised by exposing the virus to an environment which causes a topographical change, thus preventing adhesion of the virus to the host cell.
The environment may be an environment having a pH <6, and in particular may have a pH in the range 4-6.
Influenza virus replication may be explained as a series of steps, such as, for example :-
1. Adsorption.
2. Penetration.
3. Endosome Formation.
4 Endosome functions (pH 5 - 6), including a topographical change of haemagglutinin structure.
5. Disassembly of infecting virus particles and release of viral components into the cell.
6. Replication of virus ribonucleic acid and viral proteins using the infected cell enzymes and structures.
7. Virus assembly, including haemagglutinin and neuraminidase migration to the surface of the infected cell at pH greater than or equal to pH 6 — 7.
8. Release of next generation of infectious particles.
The present invention moves step 4 to precede step 1 and thus prevents the binding of the virus to the host cell so the replication cycle of the virus is not initiated.
It has been shown that influenza virus causes red blood cells to aggregate. The antigen concerned is haemagglutinin. Haemagglutinin has been shown to occur on the surface of
viruses and to be responsible for the adsorption of the virus particle onto a red blood cell and onto cells that can be infected. Haemagglutinin activity is quantitative and enables the numbers of virus particles to be estimated. In a given suspension of infectious virus particles the haemagglutinin activity is proportional to its infectivity. Genetic changes in this haemagglutinin antigen are largely responsible for the virus maintaining its infectivity in face of the host's antibody response.
The inventor's experiments show that the ability to detect haemagglutinin disappears as the pH of the allantoic fluid containing influenza virus is reduced. This in turn indicates that a reduced pH will leave virus particles with a reduced or no capacity to bind to host cells and hence disable infectivity.
It has been shown that inside an infected cell, specifically within the endosomes formed on absorption into the cell containing the infecting influenza virus, the pH changes to between pH 5 and pH 6. This lowered pH changes the shape of the haemagglutinin within the endosomes. The virus nucleic acid is released and the infection proceeds. The virus nucleic acid and its proteins are reproduced and new particles assembled within infected cells (under normal pH conditions) and with the help of the virus-releasing enzyme (neuraminidase) are released in quantity from the infected cell.
The present invention advances the normal infectious process that occurs within the virus-containing endosomes of infected cells by making the step mediated by lower than normal pH in the endosomes of the infectious cycle occur prior to cell attachment. The step change makes influenza virus haemagglutinin unable to attach the potentially infecting virus particle to cells. The change in shape of influenza virus haemagglutinin by lowered pH is a general phenomenon with all types of influenza virus and this topographical change in the haemagglutinin stops adsorption (infection) occurring.
The haemagglutinin is not destroyed or denatured; the haemagglutinin's topography is merely changed. The process of bringing forward the process of topographical haemagglutinin change differentiates this process from the other methods used to control
infections with products that denature, disintegrate, pasteurize, disinfect, and otherwise demolish and destroy virus proteins, virus lipoproteins (membranes) and virus nucleoproteins. The present invention transposes a natural change by bringing it forward to occur earlier and before cell infection.
By facilitating this change outside the infected cell by treating the air we breathe by bubbling it through a water-based solution with a lowered pH, influenza virus particles can be effectively disabled. An apparatus used for this can be a personal device (or a group device or air conditioner). It may or may not include returning the pH to neutral (pH 7) before the air is inhaled. The process might be used with and / or without masks and other air-conditioning equipment. The process could be used in crowded places on land, sea or air. The applications are air handling systems, including but not limited to air-conditioning units in buildings, air-circulation systems in aircraft and air filtration systems. Alternatively in suitable environments it may be possible merely to spray the diluted mild acid (for example, at pH 4 — pH 6) into the air of closed rooms or poultry houses or pig-sties to assist the more normal (ruthless) disinfection regimes.
Solutions containing mild acids that are readily available could be used to bubble air through to ensure disarming infectious influenza virus. The mild acids include but are not limited to vinegar (acetic acid) and its salts (e.g. sodium acetate) or other acidic compounds such as lemon juice (citric acid and its salts). The agents of change are easily accessible, low in cost and in common usage. The apparatus used can be simple or refined, personal or air-conditioners.
Other embodiments of the invention include suitably treated nose and mouth masks and / or use devices such as eastern water-cooled smoking devices and / or nasal sprays.
A further embodiment of the invention could be used in air-conditioners, air-cleaners, humidifiers and driers. This embodiment could be applied to medical wastes, biological wastes, seats and cushions, walls and curtains, floors and floor coverings, including but not limited to carpets and mats. Masks and clothes for medical workers could be
sprayed. Ambulances and stretchers could also be treated either routinely or when they have carried infected patients.
In the throat and lung passages in normal uninfected individuals the pH is around pH 7.0. The throat and its moist membranes are strongly buffered. This property neutralizes mild acid liquids introduced into the mouth and throat and it could also be expected to neutralize the effects of mild acid solutions used this invention. This is mentioned merely to show that the use of mild acid may enable clinicians to experiment with respirators containing mild acids to disarm newly formed and released influenza virus by an infected individual during throat and lung administration. [For information: in (non- influenza) throat infections, the pH can often be radically but temporarily reduced and be in extreme cases as low as pH 5.0. The pH in the throats of recovering patients invariably returns to normality, pH 7.]
Experimental Results
Haemagglutinin is the influenza antigen responsible for virus attachment to cells. It allows influenza virus to adhere to cells which is the first part of the infection process.
The following experimental results show the instability of influenza virus haemagglutinin to pH changes. The strains used were A/Eng/12/64, A/Eng/76/66, B/Eng/939/59 and B/Eng/5/66. The haemagglutinin (HA) detectable in virus containing fluids was significantly or totally reduced below pH 6.0 to 6.5. In the case of A/Eng/12/64 all the haemagglutinin activity had disappeared at pH 4.0 and below and more than 50% disappeared at pH 5.0. In the case of A/Eng/76/66 all the haemagglutinin activity had disappeared at pH 5.0 and below and more than 50% at pH 6.25. In the case of B/Eng/939/59 all the haemagglutinin activity had disappeared at pH 5.25 and below and more than 50% at pH 5.75. Finally, in the case of B/Eng/5/66 all the haemagglutinin activity had disappeared at pH 5.5 and more than 50% at pH 6.25.
Results of the effect of pH changes on four strains of Influenza Virus.
10ml of allantoic fluid of the four strains were pH adjusted with 0.1N HCl. The haemagglutinin levels [SaIk, J.E. (1944) J Immunol 49 87 - 98] were determined using chicken red blood cells.
Results of the effect of pH changes on haemagglutinin levels of four strains of Influenza
Virus.
Results Table
BDL = Below Detectable Levels NT = Not Tested
It can be seen that haemagglutinin levels decrease as the pH lowers, indicating a decreased capacity for the binding of viruses to potential host cells.
Whereas the experiments disclosed were carried out in liquids other techniques can be envisioned. Impregnating face masks with vinegar (acetic acid or sodium acetate) or other acidic compounds such as lemon juice may itself prove possible with such additional effects without blocking the pores of masks et cetera. The temperature of treatment can be useful too. One would expect a more rapid response with temperatures higher then 37 0C, for example. Virus preservation can be expected to be higher the lower the temperature.
Claims
1. A method for inhibiting viral transmission characterised by exposing the virus to an environment causing replication steps to occur out of sequence.
2. A method for inhibiting viral transmission characterised by exposing the virus to an environment which causes a topographical change to its exposed proteins, thus preventing adhesion of the virus to the host cell.
3. A method for inhibiting viral transmission according to claim 2 where the haemagglutinin protein undergoes a topographical change.
4. A method according to claims 1 and 2 where the environment to which the virus is exposed to is acidic.
5. A method according to claim 4 where the acidic environment has a pH below 6, 9preferably between 4 and 6.
5. A method according to any preceding claim where the virus is an influenza virus.
6. A device for exposing a viral particle to an environment, characterised in that the exposure causes replication steps of the virus to occur out of sequence.
7. A device for exposing a viral particle to an environment, characterised in that the exposure causes a topographical change to exposed proteins of the viral particle.
8. A device as claimed in claim 6 or 7 which incorporates an acid solution.
9. A device according to claim 6 to 8 for personal use comprising an acid solution across which air is passed.
10. A device according to claim 6 or 7 comprising a filter which exposes viral particles passing through it to an acidic environment.
11. A device for exposing an influenza virus particle to an environment, characterised in that the exposure causes a topographical change to the haemagglutinin protein of the particle.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0604000A GB2435421A (en) | 2006-02-28 | 2006-02-28 | Method for disabling influenza virus |
PCT/GB2007/000647 WO2007099296A1 (en) | 2006-02-28 | 2007-02-23 | Method for disabling viruses |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1996023A1 true EP1996023A1 (en) | 2008-12-03 |
Family
ID=36178941
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP07705278A Ceased EP1996023A1 (en) | 2006-02-28 | 2007-02-23 | Method for disabling viruses |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP1996023A1 (en) |
GB (1) | GB2435421A (en) |
WO (1) | WO2007099296A1 (en) |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3927807A1 (en) * | 1989-08-23 | 1991-03-14 | Hoelter Heinz | BACTERICIDAL AND FUNGICIDAL MATERIAL FOR THE PRODUCTION OF CLIMATE CHANNELS |
JP3280151B2 (en) * | 1994-02-02 | 2002-04-30 | 株式会社前田金属製作所 | Sterilizer for air conditioner |
JPH1045505A (en) * | 1996-08-05 | 1998-02-17 | Daiwa Kagaku Kogyo Kk | Inactivating agent for influenza virus |
CN1309305C (en) * | 2003-04-29 | 2007-04-11 | 上海家化联合股份有限公司 | Chinese herbal medicine air disinfectant |
CN1454695A (en) * | 2003-05-16 | 2003-11-12 | 北京大学 | Air filtering and purifying material and its use method |
WO2005000368A1 (en) * | 2003-06-27 | 2005-01-06 | Takahashi, Sanae | Disinfecting deodorizers, disinfecting deodorizer solutions, and method of disinfecting and deodorizing with the same |
CN1247266C (en) * | 2003-07-10 | 2006-03-29 | 吕蔺强 | Air sterilizing and freshing agent |
JP2005125141A (en) * | 2003-10-21 | 2005-05-19 | Ti Kenkyusho:Kk | Sterilization filter |
JP2005095112A (en) * | 2003-08-19 | 2005-04-14 | Mitsubishi Heavy Ind Ltd | Virus-inactivating agent and method for inactivating virus, filter having the same inactivating agent and air conditioner having the same filter |
JP4559089B2 (en) * | 2004-01-23 | 2010-10-06 | コンビ株式会社 | Virus capture spray and virus capture filter |
-
2006
- 2006-02-28 GB GB0604000A patent/GB2435421A/en not_active Withdrawn
-
2007
- 2007-02-23 EP EP07705278A patent/EP1996023A1/en not_active Ceased
- 2007-02-23 WO PCT/GB2007/000647 patent/WO2007099296A1/en active Application Filing
Non-Patent Citations (1)
Title |
---|
See references of WO2007099296A1 * |
Also Published As
Publication number | Publication date |
---|---|
GB2435421A (en) | 2007-08-29 |
WO2007099296A1 (en) | 2007-09-07 |
GB0604000D0 (en) | 2006-04-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR102251918B1 (en) | Substances, devices and methods for inactivating pathogens of aerosols, and methods for preparing the same | |
Chakhalian et al. | Opportunities for biomaterials to address the challenges of COVID‐19 | |
Sadique et al. | High-performance antiviral nano-systems as a shield to inhibit viral infections: SARS-CoV-2 as a model case study | |
Springthorpe et al. | Chemical disinfection of virus‐contaminated surfaces | |
Bray | Defense against filoviruses used as biological weapons | |
Tiliket et al. | A new material for airborne virus filtration | |
EP2340842B1 (en) | Composition for prevention of influenza viral infection comprising tannic acid, air filter comprising the same and air cleaning device comprising the filter | |
EP2314303B1 (en) | Composition for prevention of influenza viral infection comprising sumac extract, air filter comprising the same and air cleaning device comprising the filter | |
KR100695264B1 (en) | Antibiosis filter manufacture method and Antibiosis filter | |
KR20080081275A (en) | Countermeasure against infection with floating virus | |
Tharayil et al. | Contact transmission of SARS-CoV-2 on fomite surfaces: surface survival and risk reduction | |
Pagat et al. | Evaluation of SARS-coronavirus decontamination procedures | |
JP4559089B2 (en) | Virus capture spray and virus capture filter | |
CN102438601A (en) | Electrostatically charged multi-acting nasal application, product and method | |
EP1996023A1 (en) | Method for disabling viruses | |
KR101153630B1 (en) | Composition for prevention of influenza virus comprising tannic acid, air filter comprising the composition and air cleaning device comprising the filter | |
CN102088964B (en) | Electrostatically charged multi-acting nasal application product | |
US20230276798A1 (en) | Method and composition for pathogen inhibition utilizing engineered crystalline structures | |
Gupta | A Perspective of Viruses and the Outbreak of a Novel Coronavirus SARS-CoV-2 | |
WO2010082587A1 (en) | Adsorbent for suspension in air | |
JP2003210558A (en) | Air purification system and air purification filter using antibody substance | |
Janik et al. | SARS-CoV-2: Outline, Prevention, and Decontamination. Pathogens 2021, 10, 114 | |
Prince et al. | Inactivation of influenza viruses by coated respirators: in-vitro infectivity assays | |
Ghosh et al. | Clays in the Global War Against COVID-19: Why are They Preferable Over the Conventional Weaponry? | |
Castaño et al. | Fomite Transmission, Physicochemical Origin of Virus–Surface Interactions, and Disinfection Strategies for Enveloped Viruses with Applications to SARS-CoV-2 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20080929 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR |
|
17Q | First examination report despatched |
Effective date: 20090605 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED |
|
18R | Application refused |
Effective date: 20101224 |