CAN CHLORINE DIOXIDE PREVENT THE SPREADING OF

CORONAVIRUS OR OTHER VIRAL INFECTIONS?

MEDICAL HYPOTHESES

1. Department of physics, group of chemical physics, Budapest university of technology and

economics, Budapest Hungary.

2. Institute of Translational medicine and international nephology research and training center.

Semmelweis university, Budapest Hungary.

INTRODUCTION
MOTIVATION
Viruses have caused many epidemics throughout human history. The novel coronavirus is
just the latest example. A new viral outbreak can be unpredictable, and development of
specific defense tools and countermeasures against the new virus remains time-
consuming even in today's era of modern medical science and technology. In the lack of
effective and specific medication or vaccination, it would he desirable to have a
nonspecific protocol or substance to render the virus inactive, a substance/protocol,
which could be applied whenever a new viral outbreak occurs. This is especially important
in cases when the emerging new virus is as infectious as SARS-CoV-2.

AIM AND STRUCTURE OF THE PRESENT COMMUNICATION.

In this editorial. we propose to consider the possibility of developing and implementing
antiviral protocols by applying high purity aqueous chlorine dioxide (Clo2) solutions. The
aim of this proposal is to initiate research that could lead to the introduction of practical
and effective antiviral protocols to this end, we first discuss some important properties of
the CIO, molecule. which make it an advantageous antiviral agent, then some earlier
results of ClO2, gas application. against viruses will be reviewed. Finally, we hypothesize
on methods to control the spread of viral infections using aqueous ClO₂, solutions.

Corresponding author Prof.emer. Laszlo Rosivall, MD, PHD, DS. FERA. FAPS, Institute of Translational
Medicine, International Nephrology Research and Training Center. Symmetries University. Budapest
Nagyvárad tér 4. H-1089, Hungary. Tel/Fax -1-2100-DO0.
PREVIOUS EXPERIENCE AND BACKGROUND OF USING CLO₂, AS AN
ANTIVIRAL AGENT
Inactivating virus with, ClO₂ in aqueous phase to our present knowledge, an aqueous
solution of ClO₂, is able to inactivate all types of viruses. Disinfectants (in water phase) are
compared by their CT values, which is the concentration (measured in mg/L) multiplied by
the contact time (measured in minute). In CT tables., is indicated for viruses in general,
without mentioning any exemptions. For example, ac ClO₂ cording to [6l a CT value of 8.4
mg X min/L. is needed to achieve a four-orders-of-magnitude ("4 log or "99.99%")
inactivation of viruses in an aqueous medium at 25 C .

Chemical mechanism of virus inactivation: reaction of CIO,

with amino acid residues
In 1986, Noss et al. proved that the inactivation of bacterial virus (2 by ClO₂, was due to its
reactions with the viral capsid proteins, and almost no inactivation of the infectious viral
RNA occurred (8) when that was treated with ClO₂, separately. They found [19). however,
that three discrete chemical moieties in the viral protein, namely the cysteine, tyrosine,
and tryptophan amino acid residues were able to react with ClO₂, rapidly. In 1987, Tan et
al tested the reactivity of ClO₂, 21 free amino acids, ClO₂ reacted only with six amino acids
dissolved in 0.1 M sodium phosphate buffer, pH 6.0. The reaction with cysteine,
tryptophan, and tyrosine was too rapid to be followed by their technique. Three further
amino acids (histidine, hydroxy- proline, and proline) reacted with ClO₂, much more slowly,
at a measurable rate. The reactivity of the three fast-reacting amino acids (cysteine (12),
tyrosine (171, and tryptophan (271) was studied in Margerun's laboratory between 2005
and 2008. They found that cysteine had the highest reactivity among these amino acidic.
From their experimental data they calculated second order-rate constants (at pl 70, 25 C
and I M ionic strength) and obtained the following sequence: cysteine 69 x 10" M '>
tyrosine 13 x 10' Ms.> tryptophan 3.4 X to M > guanosine 5'-monophosphate 45 x 10 M.
(They studied guanosine 5'-menophosphate [18] as a model compound for guanine in
nucleic acids. Data presented here are taken from Table 3 of ref. [18). In 2007, Ogata (22
found that the antimicrobial activity of ClO₂, is based on denaturation of certain proteins,
which is primarily due to the oxidative modification of the tryptophan and tyrosine
residues of the two model proteins (bovine serum albumin and glucose 6 phosphate
dehydrogenase) used in his experiments. In 2012, it was again Ogata who showed (23]
that the inactivation of influenzas virus by CIO, was caused by oxidation of a tryptophan
residue (WI53) in hemagglutinin (a spike protein of the virus), thereby abolishing its
receptor-binding ability In this context it is interesting to remark that the spike protein of
the new coronavirus SARS CoV-2 contains 54 tyrosine, 12 tryptophan, and 40 cysteine
residues (29). If we assume that in an aqueous solution all of these residues are able to
react with ClO₂, just like the free amino acids, then the inactivation of the viruses can be
extremely rapid even in a very dilute (e, in a 0.1 mg/1) ClO₂, solution.

CLO₂, IS A WATER-SOLUBLE GAS

Although chlorine dioxide in itself is a gas, it is highly soluble in water. When both air and
water are present, ClO₂ in distributed between the two phases in an equilibrium ratio
determined by the temperature. This distribution coefficient of ClO₂, was determined by
Ishi (1] in 1958 The distribution coefficient, y = ( ClO₂; l/Cohn gives the ratio of the
concentrations expressed in the same units in the gas and the aqueous phases (e.g. g/L)
and changes as a function of the temperature. For example, at 20 "Cy= 0.0316, indicating
that in equilibrium 1 cm" aqueous phase contains (0.0316) = 31.6 times more ClO₂,
molecules than I cm' gas phase. In practice, the concentrations in the two phases are
usually given in ppm. However, these dimensionless numbers are defined in a different
way in the gas and liquid phases as ppm (V/V) and ppm (m/m), respectively. Therefore, tor
practical purposes, we need a distribution coefficient, which gives the ratio between these
concentrations. Straightforward calculation yields that the distribution coefficient in terms
of ppm is 357 times the distribution coefficient in terms of (g/L), so at 20 "C T= 11.3. Thus,
the following formula can be sed to calculate the CIO, concentration of the gas phase
being in equilibrium with a ClO₂, solution at 20 "C:
(ClO₂ )gas in ppm(V/V) = 11.3X (ClO₂, l), in ppmim/m)

INACTIVATING VIRUSES WITH CLO₂, IN GAS PHASE

The virus-inactivating reactions (the reactions of ClO₂, with the three amino acids) take
place in an aqueous medium; consequently, ClO₂ can inactivate microbes in their wet state
only. Therefore. ClO₂, gas that is moisturized can be an ideal agent against viruses both in
their wet and dry states. Viruses that are carried by water droplets could be easily
inactivated even by ClO₂, gas owing to the high solubility of ClO₂, in water. A dry ClO₂, gas
would be inappropriate as the water content of the Aquion droplet could evaporate, and
in the absence of aqueous medium the reactions of ClO₂ , slow down extremely. Indeed,
Morino reported that when applying a low concentration of ClO₂, in the gas phase against
FCV in dry state, atmospheric moisture - at least a 75-85% relative humidity - is
indispensable to inactivate viruses. The advantage of using a moisturized ClO₂, gas is that
its water content is also able to wet viruses in dry environment. Most viruses are found on
hard surfaces indoor, but a small fraction of viruses is "airborn", attached to dust particles,
which can also carry a single microbe or an aggregate of microbes. Therefore, it is a
prerequisite of an effective disinfection that all microbes in all parts of the room should be
wet and should be in contact with ClO₂, If enough aqueous ClO₂ , solution is sprayed into
the room, the droplets will saturate the atmosphere with water vapor everywhere,
moreover, the atmosphere will also contain gaseous ClO₂, everywhere. The great
advantage of this method is that H0 and ClO₂, molecules of the gas phase can reach the
microbes in every small corner of the room. Finely dispersed water droplets containing
dissolved ClO₂, can create an advantageous environment to maintain such conditions for a
longer time.
This method using bight ClO₂, concentration allows fast disinfection of rooms when
people are not present, egg intensive care units, buildings used as quarantine, or public
transport vehicles. However, the application of ClO₂, gas is limited when people are
present, as it is harmful for humans and animals above certain concentrations. The US
Occupational Safety and Health Administration (OSHA) limits the concentration of ClO₂,
gas allowed in workplace air to a1 ppm (V/V) time-weighted average (TWA) for an 8-h
exposure, and to a temporarily higher 0,3 ppm Short Term Exposure Limit (STEL) only for a
15-min period.

PREVIOUS RESEARCH ON PREVENTING VIRAL INFECTIONS

WITH GASEOUS CLO₂
Ogata realized first that ClO₂, is able to inactivate viruses even under the 0.1 ppm (OSHA
TWA) limit that is in concentrations which are not harmful to humans. In 2008, Ogata and
Shibata demonstrated that infection of mice with influenza A virus applied in an aerosol
can be prevented by ClO₂, gas present at 0.03 ppm concentration in the air, which is only
30% of the permissible TWA exposure level for humans at a workplace. They concluded
that " ClO₂, gas coiid, therefore, be unfurl a preventive tool against influenza in places of
human activity without necessitating evacuation." They have even made attempts to
decrease the incidence of flue infections among schoolchildren by applying low
concentrations of ClO₂, gas in a darkroom in spite of these promising curly results we are
not aware of any wider-scale application of this method in the last decade. There are two
problems which could hinder the widespread adoption of this method
1. With the technique applied by the above-cited authors it is not an easy tank to achieve
and maintain a very low ClO₂, concentration in a large space and for a Lang time, which is a
prerequisite of achieving a satisfactory level of virus inactivation.
2. It is not understood why low ClO₂, levels are not harmful to humans or animals and still
effective against viruses.
SIZE SELECTIVE EFFECT OF CLO₂
Although cysteine, tyrosine, and tryptophan residues can also be found in human tissues,
ClO₂, is much less toxics for humans or animals than for microbes (bacteria, fungi, and
viruses. Noszticzies et al. (20) found that the main reason for this selectivity between
humans and microbes is based not on their different biochemistries but on their different
sizes. Based on experiments and calculations using a reaction-diffusion model Noszticzius
et al. [20| found that g time of a living organism is proportional to the square of its
characteristic size (eg. its diameter), thus small ones will be killed extremely fast. Their
calculations indicated that a bacterium I um in diameter would be killed in a 300 mg/L.
CIO, solation within 3 ms and even in a much more dilute. 0.25 mg/L ClO₂, solution it
would be eliminated in only 3.6 s. During this time, ClO₂, reaches all parts of the cell and
kills I by destroying its cysteine, tyrosine, and tryptophan-containing proteins, which are
essential for life processes.

THE PROTECTIVE ROLE OF GLUTATHIONE AGAINST CLO₂,

OXIDATION IN A LIVING CELL
According to I son et al glutathione reacts with ClO₂, at a rate, which is even higher than
the rate of the very fast ClO₂, - cysteine reaction When ClO₂, contacts a living cell
containing glutathione, at first the ClO₂, concentration remains very low even at the point
of entry into the cell due to this rapid reaction. As a small molecule, glutathione can also
diffuse rapidly to the point of entry from other parts of the cell consuming most of the
ClO₂, there, and preventing it from reaching the cysteine, tyrosine. and tryptophan
residues of the proteins in the bulk of the cytoplasm. Consequently, the initial low ClO₂,
concentration cannot make too much harm
However, continuous ClO₂, entry can finally exhaust it he Cell’s glutathione (and other
antioxidant) capacity even if the cell produces swatch antioxidants continuously. At this
point, CIO, can enter into the previously protected zones of the cell and react with the
reactive ClO₂ amino acid residues, causing denaturation of the affected proteins and
ultimately cell death. The effect of glutathione and other small antioxidant molecules
present in living cells was net taken into account in the theoretical calculations of
Noszticzius Their experiments were done on a non-living and wished animal membrane,
where membrane-fixed reactive proteins were present, but glutathione and other small
molecules were absent. A living cell, however, continuously produces these antioxidants,
thus their role cannot be neglected. Indeed, looking at the experimentally measured
disinfection dynamics of a 0.25 mg/L ClO₂, solution against Escherichia coli bacteria (2) we
can see a disinfection rate, which is surprisingly fast but still about cane order of
magnitude slower than the theoretical estimate. It is reasonable to assume that the
delaying effect of these small reducing molecules is responsible for that deviation.

PROTECTION OF HUMAN TISSUES AGAINST THE

OXIDATIVE EFFECT OF CLO₂,
Human cells also contain glutathione in mM concentrations, as well as other antioxidants
like vitamin C and E which work together with glutathione to reduce ClO₂. As a human cell
is much larger than a bacterium, consequently its glutathione reserve and glutathione
production potential are also greater, so even an isolated human cell can survive much
longer in a ClO₂, environment than a planktonic bacterium. Considering that human cell is
not isolated but form tissues, their glutathione stock may be many orders of magnitude
greater than that of a planktonic bacterium. Additionally, in multicellular organism’s
circulation transports antioxidants continuously to the cells of the tissue affected by a ClO₂,
attack. helping them to survive This strengthens the size-selectivity effect, and explains
the surprising observation; that lo, solutions that are able to kill planktonic bacteria in a
fraction of a second may be consumed, because they are safe for humans to drink in a
small amount (e.g. drinking I L 24 mg/L. ClO₂, solution in two portions on a single day
caused no observable effects in humans 15).

THE EFFECT OF CLO₂, ON THE LUNG

While human tissues are not very sensitive to ClO₂, in general, lungs should be considered
differently. This is because the interalveolar septum separating the airspace of an alveolus
from the blood stream of a capillary lumen is very thin. That diffusion barrier in the human
Jung is a mere 2 am thick (1] in order to facilitate an efficient diffusional exchange of
oxygen and carbon dioxide between the air and blood, the alveolus is covered by a thin
layer of lining their called epithelial lung lining fluid (ELF) or hypophase. The ELF is only 0.2
um thick in rat alveoli (t, 13). It contains glutathione [3| and other antioxidants such as
ascorbic and uric acids (5L It is remarkable, that the ascorbic acid concentration is 2.5
times, and the glutathione concentration is more than 100 times higher in the ELF than in
the plasma. The normal function of these nonenzymatic antioxidants in the ELF is to
protect the epithelial cells from reactive oxygen species (ROS) like superoxide radicals or
hydrogen peroxide, which are toxic products of the metabolism. They can also defend the
lung against other toxic gases such as ozone (O3,), nitrogen dioxide (NO2,) or ClO₂,
However, high amounts of ClO₂, can consume all reducing agents in the ELF, at which point
ClO₂, starts to react with the epithelial cells causing a continuously growing damage to
these cells. It is known that higher concentrations of ClO₂, gas can be lethal, However, it is
reasonable to assume that the effect of ClO₂, on the lung depends not only on its con-
centration in the gas phase but also on the contact time. Thus, when considering the
impact of ClO₂, on the lung it would be logical to regard the CT (concentration) x (contact
time) product in a similar way as in the case of the microbes.

ESTIMATING THE INACTIVATION TIME OF VIRUSES IN THE

CASE OF VIRUSES,
the inactivation mechanism differs from that of bacteria or other cells. It is feasible to
assume that the inactivation time of a virus is probably much shorter than the inactivation
time of a bacterium under the same conditions (CIO; concentration, temperature, etc.),
The following arguments support this assumption:
1 Viruses are about one order of magnitude smaller than bacteria e.g., the diameter of
SAR- S CoV-2 is about 120 nm .The killing time of a virus as introduced in [20] would be 1-2
orders of magnitude shorter than that of a bacterium, the diffusion-controlled reaction
with ClO₂, would happen on a shorter time scale in the entire volume of the virus.
2. It is not necessary for do, gas to penetrate the virus in order to inactivate it. It in
enough if ClO₂ reacts with one or some of the cysteine, tyrosine, and tryptophan amino
acid residues of the spike, which are located on the surface of the virus. This means that
the theoretical Approach of ref. (20of overestimates the inactivation time of viruses. On
the one hand, because diffusion is extremely fast over a 0.1 um length scale, thus
probably it is not limiting the rate of the reactions On the other hand, ClO₂, can reach a
large part of the reactive amino acid residues of the spike without permeating through the
protein envelope of the virus.
3. Viruses do not contain protective small molecular thiols like glutathione or other small
molecular protective metabolic products, because viruses have no metabolism. In this
respect viruses should be much more vulnerable than bacteria to an attack by ClO₂.
These facts all suggest that once ClO₂, contacts the surface of a virus, it is inactivation is
quick However, a virus ready to infect a cell s typically in aqueous phase, eg. in a fluid
droplet, or in the epithelial lining fluid covering the mucous membranes. The size of these
aqueous phases is much larger than that of the virus. Therefore, in such cases, the rate-
limiting step probably is the diffusion of do, in the water and the reaction with other
substances. The time required to inactivate the virus itself would be short compared to
the time needed to transport enough ClO₂, molecules to the virus.
 SUGGESTIONS FOR PREVENTING THE SPREAD OF VIRAL
INFECTIONS USING ClO₂
Based on the previous arguments, some propositions will now be put forward on how
aqueous CIO, solutions could be applied for global and local (personal) disinfection
purposes. Many of these propositions are based on hypotheses, and therefore can only be
applied after careful research. It is a goal of the present work to initiate research to check
these hypotheses and proposals experimentally, which could lead to new applications of
high-purity CIO, solutions against viral or other infections. These ideas might be further
matured in time, but due to the threat of a global pandemic, we have chosen to move
fast.

GLOBAL PREVENTION
Disinfection of air spaces, hard surfaces and persons simultaneously with aqueous ClO₂
solutions. What we are proposing here is basically the same idea what has been already
proposed by Ogata et al. [21, 24, 25]: it is possible to create ClO₂ atmospheres which can
be safe for humans but at the same time harmful for microbes. There are differences,
however, between their proposals and ours. Ogata´s group regarded the ClO₂
concentrations (C) of the atmosphere as the sole important parameter of the treatment.
They proposed to apply a ClO₂ concentration below the 0.1 ppm (V/V) OSHA limit, for a
time that is necessary to inactivate the microbe. With such a method, however, the
necessary contact time (T) can be very long. Here we suggest regarding the CT product as
the parameter of disinfection. IN this way it is possible to apply ClO₂ concentration above
the OSHA limit but for a limited time only. The advantage of this method is that as higher
C values are applied, the necessary contact times can be much shorter. The idea will be
illustrated by a numerical example below.
Another important difference is that Ogata´s method focuses mostly on the role of the
ClO₂ gas, whereas we emphasize the importance of the simultaneous usage of ClO₂ and
H₂O gases, as confirmed by the observations of Morino et al. [16]. For this purpose, we
suggest a new way of creating a ClO₂ atmosphere: to apply aqueous ClO₂ solutions which
can establish equilibrium ClO₂ and H₂O concentrations in the atmosphere, when these are
sprayed intro the air. Aqueous solutions are also easier to handle than to maintain stable
and very low ClO₂ levels in continuous gas streams.
It is advisable to apply high-purity ClO₂ solutions for spraying to avoid any unwanted side
effects to the persons or the surfaces treated. High-purity ClO₂ solutions evaporate
without any residue or trace.

An illustrative numerical example. Let us assume that we want to disinfect a closed space
by spraying some aqueous stock ClO₂ solution into it. The equilibrium ClO₂ concentration
𝐶𝑎𝑖𝑟 in the gas and 𝐶𝑤; 𝑒 in the liquid please can be calculated from the vapor-liquid
equilibrium distributions measured by Ishi [11]:

and from the component balance for ClO₂:

𝑉𝑤. 𝐶𝑎𝑖𝑟 = 𝑉𝑤. 𝐶𝑤. 𝑒 + 𝑉𝑎𝑖𝑟. 𝐶𝑎𝑖𝑟

where 𝑉𝑎𝑖𝑟 is the volume to be disinfected, 𝑉𝑤 is the volume of the ClO₂ stock solutions,
and 𝐶𝑤 is its ClO₂ concentration. whit the help of the above two equations 𝐶𝑤. 𝑒 can be
calculated as

Suppose we apply 𝑉𝑤 = 20 𝑚𝐿. of 𝐶𝑊0 = 40 𝑝𝑝𝑚 (m/m) aqueous stock ClO₂ solutions in a
𝑉𝑎𝑖𝑟 = 1𝑚3closed space.
At 20 ⁰C the value of the distributions coefficient is ϒ = 0.0316 (data of Ishi [11]) when all
concentrations are given in the same unit (e.g., in mg/L), and it is ϒ𝑝𝑝𝑚 = 11.3 (see section
ClO₂ is a water soluble gas) when ppm (m/m) and ppm (V/V) are used in the aqueous and
gaseous phases, respectively. Substituting our data, the results are

𝐶𝑤. 𝑒 = 0.025ppm(m/m),

𝐶𝑎𝑖𝑟 = ϒ𝑝𝑝𝑚 = 0.29ppm(V/V)

This result is just below the OSHA STEL (Shorter Term Exposition Limit) value which is 0.30
ppm (V/V) for 15 min. According to OSHA, STEL is the acceptable average exposure over a
short period of time - usually 15 min – as long as the time-weighted average (TWA) is not
exceeded. If a person is exposed to 0.30 ppm for 15 min, and right after that he or she
stays in a ClO₂-free atmosphere for 30 min, then the TWA value for this whole 45 min
period is just the acceptable 0.10 ppm. All this means that an exposure of a person to a
0.30 ppm ClO₂ atmosphere for 15 min on a single occasion, or even applying that
treatment periodically with 30 min pauses within an 8 h period, should not cause any
health problems.

QUESTIONS AND REMARKS

1. It is major questions, whether or not a 15-min stay in a o.29 ppm (V/V) ClO₂
atmosphere is enough to inactivate the viruses present? Regarding the wet
atmosphere we can assume that the viruses are also wet, or even that they can be
found in small water droplets containing 0.025ppm (m/m) ClO₂. We have no direct
data for the inactivating time of viruses in such a solution, but we have an
estimated 15 ± 5 skilling time value for an E. coli bacterium in a 0.25ppm (m/m)
ClO₂ solution [2]. It is reasonable to assume that the killing time would be 10 times
more dilute solutions, i.e., 150 s =2.5 min. As viruses are probably inactivated
faster than bacteria, and 15 min is six times longer than the estimated 2.5 min for
E. coli, such a method can be successful, at least in theory.
2. To the such a method, we suggest constructing special disinfecting rooms with
larger volume. Starting such experiments would be highly desirable, because this
method could be an effective nonspecific defense against all types of viruses and
could help to contain viral outbreaks.

Local prevention. Personal disinfection techniques against viral

infections

Disinfection of the mouth and the upper respiratory track with gargling . The
current epidemic coronavirus is known to be present in the mouth and both in the upper
and lower respiratory tract, especially in the lung. The incubation period of the disease is
several days, but the virus can often be detected in samples taken from the upper
respiratory track a few days before symptoms appear. As discussed in a previous chapter,
chlorine dioxide will certainly inactivate the virus. With gargling, the upper respiratory
track is accessible except for the nasal cavity, but that is also accessible using e.g. nose
drops or impregnated tampons. These parts can be disinfected by rising them regularly
with high-purity chlorine dioxide solutions available commercially [31], thus the number of
the viruses can be significantly reduced in the mouth and in the upper respiratory tract.
We cannot be sure that such a treatment would be enough to prevent the development
of the illness, as viruses living in other parts of the body can survive. However, inactivating
part of the viruses with such a treatment surely helps the immune system to fight against
the disease. In this respect, it is interesting to remark that.
Japanese researchers have proven, that regular gargling with drinking water has reduced
the incidence of upper respiratory trad infections to a statistically significant extent. The
effect was explained by the fact that the drinking water used in the experiments contained
05 mg/l of chlorine, which was used to disinfect the water. We remark here, that in
certain places chlorine dioxide is applied for the disinfection of drinking water instead of
chlorine.

Disinfection of the lower respiratory track.

The first problem is how ClO₂, can be safely introduced into the lower respiratory tract.
For this purpose, any inhalation technique could be applied using aerosols of water
droplets containing ClO₂.
The second and more important problem is how much ClO₂, can be inhaled without
damaging the lung? It would be helpful to know the dose of ClO₂, that is not yet harmful
for the lung. To our knowledge such direct data are not available in the literature, but can
be calculated from other data. The starting point for such a calculation is the OSHA STEL
value, according to which 0.30 ppm ClO₂, in the workplace atmosphere is tolerable for a
15 min period without any damage. The volume of air inhaled by a worker during 15 min is
15 times the so-called "minute volume ventilation" According to Table 3 of ref. during light
activities eg. when sitting in a car the minute volume is around 12 L. thus the total inhaled
air is about 180L In the case of 0.30 ppm concentration the total inhaled amount of ClO₂,
is 54 ul., which is (at 20 "C) 2.25 umol e0.15 mg ClO₂, Assuming a more vigorous activity it
can be two times more, 030 mg. This rough calculation indicates that approximately this is
the amount of ClO₂, which can be tolerated by the lung The OSHA limit probably applied
high safety factors, thus the real limit should be higher. We suggest that animal
experiments should be performed to obtain experimental values for the pulmonary
toxicity of ClO₂. Furthermore, it would be important to check in additional animal
experiments, whether ClO₂, applied in a nontoxic amount is able to treat infections of the
lung caused by bacteria or viruses.

CONCLUSION
 In this editorial, we summarized the unique properties of chlorine dioxide, which make it
an ideal and nonspecific antimicrobial agent at concentrations harmless to humans, and
we reviewed previous research on preventing viral infections with gaseous ClO₂,, Based on
this background, we suggested some novel hypothetical methods using chlorine dioxide to
disinfect rooms, prevent human infection, and slow down viral spread. These are
nonspecific methods, which could be used against any newfound virus as a first line of
protection until effective specific countermeasures are developed.
Conflict of interest Zoltan Noszticzius, Maria Wittmann and Kristof Kaly-Kullai are co-in-
vectors of the European patent 2069232 "Permeation method and apparatus for
preparing fluids containing high purity chlorine dioxide". Zoltán Noszticzius is a founder
and owner of the Solumium Ltd (a company producing chlorine-dioxide), while Kristóf
Kaly-Kullai is its payed employee.

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