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https://www.heighpubs.org/hjcv 022
https://doi.org/10.29328/journal.ijcv.1001031
Research Article
COVID-19 New variant and air
pollution relationship: how airborne
mutagens agent can act on genoma
viruses expression: Hypothesis of
work
Luisetto M1
, Naseer Almukthar2
, Gamal Abdul Hamid3
, Tarro G4
,
Khaled Edbey5
, Nili BA6
, Ghulam Rasool Mashori7
, Ahmed
Yesvi Rafa8
and Latyshev O Yu9
1
IMA Marijnskaya Academy, Environmental Toxicology, Italy
2
Professor, Department of Physiology/College of Medicine University of Babylon, Iraq
3
Professor, Hematology Oncology, University of Aden, Aden, Yemen
4
President of the T & L de Beaumont Bonelli Foundation for Cancer Research, Naples Italy
5
Professor, Department of Chemistry, University of Benghazi, Libya
6
Innovative Pharmaceutical Product Development Specialist, USA
7
Full Professor of Pharmacology, Peoples University of Medical and Health Sciences for Women,
Nawabshah, Pakistan
8
Founder and President, Yugen Research Organization, Western Michigan University, MI, USA
9
IMA Academy, President, Russian Federation
More Information
*Address for Correspondence: Luisetto M, IMA
Marijnskaya Academy, Environmental Toxicology,
29121 Italy, Te: +393402479620;
Email: maurolu65@gmail.com
Submitted: February 06, 2021
Approved: February 15, 2021
Published: February 16, 2021
How to cite this article: Luisetto M, Almukthar N,
Hamid GA, Tarro G, Edbey K, et al. COVID-19
New variant and air pollution relationship: how
airborne mutagens agent can act on genoma
viruses expression: Hypothesis of work.
Int J Clin Virol. 2021; 5: 022-031.
DOI: 10.29328/journal.ijcv.1001031
Copyright: Ā© 2021 Luisetto M, et al. This is
an open access article distributed under the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the
original work is properly cited.
Keywords: Air pollution; Environmental
toxicology; COVID-19 new variant; Mutagen;
Particulate matter; No2; Benzo-a-pyrene; Cause-
eļ¬€ect relationship; Direct or indirect actions
OPEN ACCESS
Introduction
Coronaviruses are a group of related RNA- viruses that
cause diseases in mammals and birds. They cause respiratory-
tract infections that can range from mild to lethal.
Mild illnesses in humans include some cases of the common
cold (which is also caused by other viruses, predominantly
like the rhinoviruses), while more lethal -varieties can cause
SARS, MERS, and COVID-19 disease.
The irst reports of a coronavirus- infection in animals
occurred in the late 1920-1930 s, when an acute respiratory
infection of domesticated chickens emerged in the North
America.
Abstract
Before actual COVID-19 pandemia coronavirus was not so dangerous like now.
In December 2019 - January 2020 in Wuhan ļ¬rst and then in other places this coronavirus was responsible of a ļ¬rst wave of severe
pulmonitis responsible of many deaths.
Wuhan and other region involved ļ¬rst was high level air polluted and industrial area.
New COVID -19 variant in last part of 2020 and in ļ¬rst month of 2021 was responsible of great diļ¬€usion of this pandemic disease.
UK, South Africa and brasilian new variant show higher diļ¬€usion then the ļ¬rst wave of COVID-19.
Aim of this work is to analyze relationship with air pollution and the possibility that mutagen substantia inside of this microenvironment can
produce new variant trough an genetic pressure process.
RNA viruses are normally subjected by natural mutation but some phenomena can contribute to accelerate this process and their airborne ā€“
aeresols microenvironment is relevant.
Some air pollutants are recognized as mutagen factors by literature.
COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work
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https://doi.org/10.29328/journal.ijcv.1001031
The virus was later known as an infectious bronchitis-
virus (IBV).
The most recent common ancestor of all coronaviruses is
estimated to have existed as recently as about 8000 before
common era, and some models back about 50 million years,
this imply a long term coevolution with bat and avian species.
Bats and birds, as warm-blooded lying vertebrates, are
considered natural reservoir for the coronavirus gene pool.
In last 2020 and in irst month of 2021 new COVID 19
VARIANT was responsible of great spread of the disease more
higher then in the irst wave.
Because relevant implication in public health politics it is
really crucial to investigate some factor that can be considered
to explain this phenomena.
If RNA virus are involved in various kind of natural
mutation process the relationship with some Polluted area
and new variant explosion is interesting fact to be observed.
South UK, Manaus ā€“ Brazil amazon zone and south Africa
show a characteristic air pollution condition and the same
it is interesting to observe that new variant emerged. (see
researche article Deforestation, air pollution and Brasiliant
COVID-19 variants Luisetto, et al. Jan 2021. Preprint
Researchgate).
Form CDC website New Variants of the Virus that Causes
COVID-190
Updated Jan. 28, 2021
ā€œMultiple variants of the virus that causes COVID-19 are
circulating globally:
The United Kingdom (UK) identi ied a variant named
B.1.1.7withalargenumberofmutationsinthefallof2020.This
variant spreads more easily and quickly than other variants.
In Jan. 2021, experts and researcher in the UK reported that
this variant may be associated with an increased risk level of
death compared to other variant viruses, but more research
studies are needed to con irm this inding. It has since been
detected in many countries around the world. This variant
was irst detected in the US at the end of Dec. 2020.
In South Africa S.A., another variant called B.1.351 emerged
(Independently of the B.1.1.7). Originally detected in early
October 2020, B.1.351 shares some mutations with B.1.1.7.
Cases caused by this variant have been reported in the US at
the end of Jan- 2021.
In Brazil, a variant called P.1 emerged that was irst
identi ied in travelers from Brazil country, who were tested
during routine screening at an airport in Japan, in early Jan.
This variant contains a set of additional mutations that may
affect its ability to be recognized by antibodies. This variant
was irst detected in the US at the end of January 2021ā€
And from WHO Coronavirus disease (COVID-19): Virus
Evolution Dec. 2020.
ā€œWhen a virus replicates or makes copies of itself, it
sometimes changes a little bit. These changes are named
ā€œmutations.ā€ A virus with one or several new mutations is
referred to as a ā€œvariantā€ of the original virus.
So the more viruses circulate, the more they may change.
These changes can occasionally result in a virus variant that is
better adapted to its environment compared to the original-
virus. This process of changing and selection of successful
variants is named ā€œvirus evolution.ā€
Some mutations can lead to changes in a virusā€™s
characteristics, such as altered transmission (it may spread
more easily) or severity (causing more severe- disease).
Related velocity: Some viruses change quickly and others
more slowly.
SARS-CoV-2 tends to change more slowly than others such
as HIV or in luenza viruses. This could in part be explained
by the virusā€™s internal ā€œproofreading- mechanismā€ which can
correct the ā€œmistakesā€ when it makes copies of itself. Scientists
-and researcher continue to study this mechanism to better
understand how it works.ā€
Genetic Variants of SARS-CoV-2ā€”What Do They Mean?
Adam S. Lauring, et al: JAMA. Published online January 6,
2021. doi:10.1001/jama.2020.27124.
ā€œOver the course of the severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) pandemic, the scienti ic, and
public health institutions have had to respond to new viral
genetic- variants. Each one has triggered a lurry of the
media attention, a range of reactions from the scienti ic
community, and calls from governments to either ā€œstay
calmā€ or pursue immediate- countermeasures. While many
scientists were initially skeptical about the signi icance of the
D614G alteration, the emergence of the new ā€œUK variantā€ā€”
named lineage B.1.1.7ā€”has raised widespread concern.
Understanding which variants are concerning, and why,
requires an appreciation of virus- evolution and the genomic
epidemiology of SARS-CoV-2. Mutations arise as a natural by-
product of viral -replication. RNA- viruses typically have an
higher mutation rates than the DNA viruses. Coronaviruses,
make fewer mutations than most RNA- viruses because
they encode an enzyme that corrects some of the errors
made during replication. In most cases, the fate of a newly
arising mutation is determined by natural -selection. Those
that confer a competitive- advantage with respect to viral
replication, transmission, or escape from immunity will
increase in frequency, and those that reduce viral itness tend
to be culled from the population of circulating- viruses. But
mutations can also increase and decrease in frequency due to
chance events.
COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work
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https://doi.org/10.29328/journal.ijcv.1001031
In example, a ā€œfounder effectā€ occurs when a limited
number of individual viruses establish a new population
during the transmission. The mutations present in the
genomesoftheseviral-ancestorswilldominatethepopulation
regardless of their effects on viral itness. This same interplay
of natural- selection and chance events shapes virus evolution
within hosts, in communities, and across countries. Although
the terms mutation, variant, and strain are often used inter-
changeably in describing the epidemiology of SARS-CoV-2,
the distinctions are important. Mutation refers to the actual
change in sequence: D614G is an aspartic acid-to-glycine
substitution at position 614 of the spike- glycoprotein SPG.
Genomes that differ in sequence are often named variants.
This term is somewhat less precise because 2 variants can
differ by 1 mutation or many. Strictly speaking, a variant is
a strain when it has a demonstrably different phenotype (a
difference in antigenicity, transmissibility, or virulence)ā€
(Fiures 1,2 ).
The new -variant is correlated with a rapid increase in the
COVID-19 incidence. This increase was reported in South- East
England.Analysisusingviralgenome-sequencedataidenti ied
a large proportion (> 49% - 50%) of cases that belonged to a
new single lineage. Overall, around 5% to 10% of all COVID-19
cases are regularly sequenced in the UK. As of 26 Dec. 2020,
about more than 3000 individuals had been identi ied with
this virus variant in England, with the earliest case identi ied
from 20 Sep. 2020. Several countries had reported sporadic-
cases caused by the new variant from other EU/EEA countries
(Belgium, Denmark, France, Germany, Iceland, Ireland, Italy,
Netherlands, Norway, Portugal, Spain and Sweden) and
globally (Australia, Canada, Hong -Kong, Israel, Japan, Jordan,
Lebanon, South Korea, Switzerland, Singapore).
South Africa S.A reported another SARS-CoV-2 variant of
potential concern, designated 501.V2 that was irst observed
in samples from Oct. and since then evolved to be the dominant
circulating variant in South Africa (From LNS).
FIG. N 3. FROM By Dr. Liji Thomas, MD 2020 SARS-CoV-2
genome variants in India.
ā€œMapping of higher frequency amino acid mutations on
Nucleo-capsid and Spike proteins. The mutations are marked
in red color on the surface representation of each protein. In
the Spike protein, all the domains are highlighted in different
colors, including NTD, RBD, HR1, Fusion peptide region, HR2,
TM, and CT domains. The cleavage sites are also marked onto
the structure
Mutations and Protein Effects:
The investigators also looked at the mutant- proteins
Figure 1: A - Phylogenetic tree: showing the relationship of lineage B.1.1.7 (20B/501Y.V1, orange branch and tips) to other circulating-
lineages. The long branch length for this lineage reļ¬‚ects the fact that it accumulated a signiļ¬cant number of mutations prior to being discovered.
B, Frequencies of circulating lineages over the time. Lineages are colored as in the tree, with lineage B.1.1.7 (20B/501Y.V1) shown in orange
(From JAMA).
COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work
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expressed as a result of amino- acid AA substitutions across
the 104 genomes. There were 53 point of mutations, of which
29 resulted in missense- mutationsā€ (Liji Thomas).
When studied in relation to the proteins affected, the
scientists found that most variations were in non-structural
protein (nsp) 6, in 68 genomes, with nsp 12 in 65, nsp 3 in 62,
and P13L, a nucleocapsid protein, in 53. One of the commonly
found worldwide- mutations, D614G, in spike- protein, was
found in only 26 genomes.
The researchers and scientist then followed the frequency
of mutation with respect to the type of change in the amino-
acid AA. They found that in about 44%, the amino acid was not
changed, which indicates that perhaps the mutation caused a
slight- change in the shape or function of the protein. The same
thing was observed with very frequently found mutations, like
as P13L.
In some other kid of mutations, the type of amino acid AA
was quite different, with a hydrophobic-to-polar or charged
type of alteration. One example is that of the addition of a
charged residue to the frequently mutated position T1198K
in nsp3, or the loss of a charged- group with the important
spike- protein SPM- mutation D614G. Such a changeover to a
residue with a positive- charge may possibly result in more
signi icant effects on the structure and function of the protein
involved. (From By Dr. Liji Thomas, MD 2020 SARS-CoV-2
genome variants in India).
Material and methods
With an observational and visual method a literature
search was performed in biomedical database.
Some relevant igure are presented to better explain the
meaning of this work.
An experimental hypothesis is submitted in order to verify
what fended in literature research.
After this phases a global conclusion is submitted to the
researcher to be more veri ied in larger scale.
Figure 2: A new SARS-CoV-2 variant referred to as SARS-CoV-2 VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant
01), has been declared by the British -authorities. The variant was detected via genomic- sequencing in the UK. It is deļ¬ned by multiple spike
protein mutations (deletion 69-70, deletion 144, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H) present.
COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work
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https://doi.org/10.29328/journal.ijcv.1001031
Results
From literature
According A Ducatti, et al: ā€œMutagenic activity of organic-
extracts of airborne particulate matter- PM at four different
sites within the urban area of the city of Porto- Alegre, Brazil,
was investigated using the Salmonella/microsome assay,
with the Kado micro-suspension method. The extracts were
obtained by sonication, sequentially extracted according to
polarity, with cyclohexane (CX) and dichloromethane (DCM)
solvents. The different fractions were tested for mutagenicity
with the Salmonella typhimurium strains TA98, TA98NR
and TA98/1,8-DNP6, without S9 mix metabolic activation. A
positive (+) frameshift mutagenic response was observed for
non-polar (CX) and/or moderately polar (DCM) compounds
at the different sites. The responses varied at different year
seasons, and the highest revertants per m3 (rev/m3) values
were observed at the site subject to the strongest in luence
of automotive- vehicles (site 3) in spring (17.13 rev/m3) in
DCM fractions, and in summer (13.01 rev/m3) in CX fractions.
The responses observed for the TA98NR and TA98/1,8-DNP6
strains suggest the contribution of nitro-compounds to the
mutagenic activity observed. Although there appears to be
an indicative association between the increased mass per
unit volume of air (TSP) and the mutagenicity of organic-
extracts of airborne particulate matter in the present study,
the Salmonella/microsome assay was a sensitive method
to de ine areas contaminated by genotoxic- compounds,
even in samples that present TPS values acceptable by the
environmental- quality standards established by lawā€[1].
Erdinger L, et al: ā€œAmong other substances, sulphur
dioxide (SO2
), nitric oxide (NO) and nitrogen dioxide (NO2)
are parameters which are routinely measured to describe
the basic air -quality. Organic extracts of airborne particulate
matter PM contain mutagenic chemical compounds of
different origins. The aim of the study was to ind correlations
between routine- monitoring data and mutagenic activity of
organic extracts of simultaneously drawn samples.
Specimens were collected over a period of 2 years at
8 sampling sites in south-west Germany. Simultaneously,
concentrations of NO, NO2
, and SO2
were measured on-line
within the framework of the of icial air monitoring network of
Baden-WĆ¼rttemberg, Germany. Dust samples were collected
for biotesting using high volume air -samplers equipped
with glass ibre ilters. After sampling was completed, ilters
were extracted and samples were prepared for biological
testing. Mutagenic activity was tested by means of the plate
incorporation assay (Ames test) using S. typhimurium TA98
and TA100 tester strains. During the irst year of the study,
all tests have been performed with and without metabolic-
activation. A series of tests has been performed in parallel
with TA98 and TA98NR.
Comparison of Ames- test data obtained with and without
metabolic- activation indicates no statistically signi icant
difference between the both methods. During the second year
of the study, all tests have been performed without metabolic
activation. Average- yearly activities at the sampling sites
were between 1 and 27 Revertants per m3 (Rev/m3).
High -activities were preferably found at congested sites
(Karlsruhe, up to 95 Rev/m3). Peak values of over 100 Rev/
m3 were found in other places where pollution by traf ic is
signi icantlylower.Thereasonforthesehighlevelvaluesisnot
evident. Tests performed using TA98NR tester strain indicate
a signi icant share (average 31%) of compounds requiring
activation by nitro-reductase for mutagenic activity. Average
mutagenic- activity can be correlated to routine monitoring
parameters. Comparison of averaged data for particular
sampling sites indicates signi icant correlation between
nitric- oxide and mutagenic activity in TA98 (r2
= 0.90),
while correlation between nitrogen dioxide (0.84) or sulphur
dioxide (0.52) and mutagenic -activity is weaker. For TA100,
correlations are generally weaker than for TA98. Comparison
of data for mutagenic activity and routine monitoring data of
distant sites being sampled simultaneously shows parallel-
behaviour.Results from this study show that mutagenic-
activity can be compared to seasonal and local variations of
gaseous indicator air pollutants. Tester strain TA98 generally
shows the best correlations. Although pollution by particle-
bound mutagenic substances is signi icantly higher during
the cold -season than during summer on average, mutagenic-
activity of airborne dust is not a continuous effect. During
winter, peak levels as well as low pollution periods can
occur. Even during winter time mutagenic activity can reach
very low- levels typical for summer-time. Comparison of
results for distant sampling sites where samples have been
collected simultaneously indicate that ā€˜classicalā€™ indicators of
air- pollution and bacterial mutagenicity of organic- extracts
from airborne particulate matter are in luenced by connected
effects. Seasonal trend of mutagenic activity, in particular,
is similar to the concentrations of nitrogen- oxide. NO is a
strong indicator for vehicle exhaust gases. It is concluded
that the average mutagenic- activity at particular sites can be
estimated using NO- concentrations as an indicatorā€ [2].
ā€œThe standard sex-linked recessive lethal test was used
to test whether NO2
induces lethal- mutations in male germ-
cells of Drosophila in the presence or absence of alkylureas.
Methylurea, ethylurea and NO2
alone did not enhance
the mutation frequency signi icantly. Highly signi icant
enhancement in mutation frequency was observed when
adult lies were exposed to NO2
(150 - 280 ppm) for 3 h after
ingestion of methylurea (0.1 M) or ethylurea (0.1 M) for 2
days. Oral- administration of ethylnitrosourea and also of
methylurea or ethylurea that had been exposed to NO2
in vitro
were more effective in increasing the mutation frequency than
methylurea or ethylurea combined in vivo with NO2
. These
results suggest that ingested alkylurea is converted in vivo
COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work
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by inhaled- NO2
to highly mutagenic nitrosoalkylurea and/or
other mutagens. No signi icant enhancement of the mutation-
frequency was observed when lies were fed on methylurea
solution after they had been exposed to NO2
ā€ [3].
Mutat Res Oct-Nov 1982
Mutagenicity of airborne particles
H Fukino, S Mimura, K Inoue, Y Yamane
ā€œThe mutagenicity of airborne- particles was studied in the
Ames Salmonella -system. The mutagenic activity of benzene
extracts from airborne- particles was more active in strain
TA98 in the presence and absence of S9 mix than in strain
TA100. The presence of mutagens, other than benzo[a]pyrene
(B[a]P), which did not require S9 mix, was indicated. The
monthlyvariationofdirect-actingmutagenicactivityshoweda
pattern similar to that of B[a]P at atmospheric- concentration.
The monthly variations of atmospheric NO, NO2
, NO-2 and
NO-3 concentrations were also similar to that of the direct-
acting mutagenic- activity. Atmospheric concentrations of
heavy metals such as Pb, Zn, Cd, V and Cu were also found to
be related to direct-acting mutagenic activity. These results
suggest that emissions from automobiles, home heaters
and power plants and so on. May be a primary source of
atmospheric, direct-acting mutagens. It is suggested that
secondary direct-acting mutagens might be partly formed by
the nitration of polycyclic- aromatic hydrocarbons (PAH) with
NO2 in the atmosphere because concentrations of B[a]P, NO2
and NO-3 increased simultaneously when the highest direct-
acting mutagenic activity was observedā€ [4].
Yet, pollution is the largest environmental cause of
disease and death in the world today, responsible for an
estimated about 9 million premature deathsā€ stated The
Lancet Commission in 2017. This phenomenon represents
an alarming- threat for human health, as a major cause of
respiratory and cardiovascular CV pathologies as well as
infertility. Those atmospheric pollutants have severe impacts
on the environment and participate in climatic change,
acidi ication, eutrophication, and ecosystem disturbances.
Several international and national organizations (WHO, EEA,
and INERIS) aim at reducing the global emission of pollutants,
thanks to environmental policies as Kyoto and Gothenburg
protocols signed in 1997 and 1999, respectively. After that, an
encouraging decrease in air pollutantsā€™ levels was measured
between 2000 and 2015. Atmospheric- pollutants can be
classi ied into four families: classical, indoor, and organic or
inorganic air pollutants. Among the classical ones, which are
the principle in amount, sulfur dioxide (SO2
), particle matter,
ozone (O3), and nitrogen oxide (NOx) species are found.
The term NOx refers to a wide range of nitrogen-derived
compounds, where nitric oxide (NO) and nitrogen dioxide
(NO2
) are predominant. Those compounds can be naturally
produced at low level by lightnings [4] and volcanic eruptions.
NOx is mainly generated by anthropogenic activity (road
transport, energy production, industry, and agriculture.
NO and NO2
, thanks to their chemistry properties
mentioned earlier, are highly diffusible through living
membranes and exhibit a strong reactivity [5].
Related eļ¬€ect of air pollution by benzo -a- pirene
ā€œThe purpose of this research study was to reveal the
pollution characteristics of ambient PM2.5ā€“bound benzo[a]
pyrene (B[a]P) in Beijing and to assess the lifetime cancer-
risk from respiratory pathway exposure. The average daily
dose was evaluated by the annual concentrations of ambient
PM2.5ā€“bound B[a]P, combined with Chinese human exposure
factors and the age sensitivity factors. The 70-year lifetime
cancer risks of different groups were assessed by the exposure
assessment and stochastic analysis -method recommended
by California Environmental Protection Agency CEPA. The
groups were divided by age and gender. The results showed
that the ambient PM2.5ā€“bound B[a]P concentration during
the cold season was 15.7 times greater than that during the
warm season in Beijing. The annual -average concentrations
of PM2.5ā€“bound B[a]P in outdoors and indoors were 1.67ā€Æng/
m3 and 1.04ā€Æng/m3, respectively, which exceeded the limit
of Chinese National Ambient Air- Quality Standard. The
cancer- risks of PM2.5ā€“bound B[a]P in males, females, and
the general -population were 9.085ā€ÆƗā€Æ10āˆ’6, 8.050ā€ÆƗā€Æ10āˆ’6,
and 8.740ā€ÆƗā€Æ10āˆ’6, respectively. The cancer- risk constituent
ratios of ambient PM2.5ā€“bound B[a]P in early life (ā‰¤16ā€Æyears
of age) for males, females, and the general population were
70.9%, 71.4%, and 71.3%, respectively. The malesā€™ cancer risk
of PM2.5ā€“bound B[a]P in Beijing was higher than that of the
females. The early- life cancer risk exposure to PM2.5ā€“bound
B[a]P should be paid more attentionā€ [6].
Remington KM, et al: in article ā€œHighly mutagenic bypass
synthesis by T7 RNA polymerase of site-speci ic benzo[a]
pyrene diol epoxide-adducted template DNAā€.
ā€œWe have previously developed an in vitro- system IVS that
allows quantitative evaluation of the idelity of transcription
during synthesis on a natural template in the presence of
all four nucleotides. We have employed this system using a
TAA ochre codon reversion- assay to examine the idelity of
transcription by T7 RNA polymerase past an adenine residue
adducted at the N6-position with (-)-anti-trans- or (+)-anti-
trans-benzo[a]pyrene diol epoxide (BPDE). T7 RNAP was
capable of transcribing past either BPDE isomer to generate
full-length run-off transcripts. The extent of bypass was
found to be 32% for the (-)-anti-trans-isomer and 18% for
the (+)-anti-trans-isomer. Transcription past both adducts
was highly- mutagenic. The reversion frequency of bypass
synthesis of the (-)-anti-trans-isomer was elevated 11,000-
fold and that of the (+)-anti-trans-isomer 6000-fold, relative
to the reversion frequency of transcription on uneducated-
template. Adenine was misinserted preferentially, followed
by guanine, opposite the adenine adducted with either BPDE
isomer. Although base substitution errors were by far the
COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work
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Figure 3: From By Dr. Liji Thomas, MD 2020 SARS-CoV-2 genome variants in India.
Figure 4: eļ¬€ect of No2.
COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work
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most frequent mutation on the adducted template, three- and
six-base deletions were also observed. These results suggest
that transcriptional errors, particularly with regard to damage
bypass, may contribute to the mutational- burden of the cell.ā€
[7].
Experimental hypotesys project
In order to verify the effects of someaereosol
microenvironment it is possible to think to observe effect in
various vials containing in equal way:
Particulate matter, benzo- a pyrene and other air pollutant
in an antmosphere rich in NO2
(and like very polluted
industrial city examples).
Different vial containings in separated way
Animal cells; Bacterial cells; Virus DNA particles, Virus
RNA particle. (Plus eucaritota cell or not to verify effect of
RNA virus translation).
Time of exposition: from 30 days to 6 month.
Other condition: various level of humidity and ozone,
and under different level of sun light irradiation (but also in
similar way like the sun light in a ozone layer loss region),
lightning or not.
After this sample experiment the data must be collected
and statistically analyzed to verify level of mutation of genetic
materials.
Discussion
From literature observed many mutation are observed in
COVID-19 this involved nucleocapside and spike protein) and
this are responsible in increased transmission and severity
level of the disease.
Spontaneous phenomena are responsible in many RNA
virus evolution and also by environmental pressure.
But it is interesting to observe that some air pollutants like
NO2 and particulate matter (and carried substatie like benzo-
a-pyrene) can produce a mutagen micro-environment that
can contribute in emerging of new variants.
Mutagens that can act also as indirect factor (involving a
eucariote translation of information).
In some current decontamination sterilization procedure
are used UV ray that with a physical way produced irreversible
damages to genetic materials of bacteria and virus so it is
possible to consider that mutant agent that currently produces
damages in human cells ( and cell death) they can produce
damages also in Rna -virus.
So it is possible to submit to the researcher the conclusion
that an airborne microenvironment with mutagen agent inside
can produce new variants also in some RNA -virus expression
in higher way vs. without mutagen agent presence (direct or
in indirect way).
It must to be considered the complex of RNA virus,
Particulate matter covered with mutagen susbtantie and
pulmonary cell infected involved in virus reproduction
-replication (Figures 7,8).
Pathology and Pathogenesis of SARS-CoV-2 Associated
with Fatal Coronavirus Disease, United States
Roosecelis B Martines, et al: Finally: Relevant for this
phenomena are: time of exposition, kind of mutagen molecule,
carriers, aeresols microenviroment, direct or indirect damage,
reversible or irreversible action, ef iciency of variant in virus
survivor and in transmission.
Conclusion
Observing the literature reported a conclusion can be
submitted to the researcher:
As hypothesis of work it is crucial to investigate the role
played by some air pollutant in some world region in produce
genetic modi ication and select respiratory virus new variant.
Before actual pandemia coronavirus was not so dangerous
like COVID-19.
A real fact that this virus spread form really polluted area
like WU-HAN or other world region like.
North Italy and that new variant was observed in South
UK, MANAUS, South Africa.
Ethical consideration: All ethical rules respected.
Figure 5: Khaya senegalensis Seeds.
Figure 6: benzo ā€“ a- pirene.
COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work
https://www.heighpubs.org/hjcv 030
https://doi.org/10.29328/journal.ijcv.1001031
Figure 7: PM2.5 exposure induces pulmonary- inļ¬‚ammation and ļ¬brosis. (A) Lung sections from ļ¬ltered -air (FA) and particulate matter
(PM2.5)-exposed mice were stained with hematoxylin and eosin (H&E) and Sirius red staining at 200Ɨ magniļ¬cation. (B-E) After exposure for
12 weeks, the mRNA- levels of ļ¬brotic- genes collagen I and transforming growth factor Ī² (TGF-Ī²) in lungs (B, C) and the level of inļ¬‚ammatory
factors- interleukin 6 (IL-6) and tumor necrosis- factor Ī± (TNF-Ī±) in serum (D, E) were measured by qPCR and enzyme linked immunosorbent-
assay (ELISA) kits, respectively. Data are presented as mean Ā± standard deviation (SD); *p < 0.05, **p < 0.01 vs. FA group. Form TMT-
Based Quantitative Proteomics Analysis Reveals Airborne PM2.5-Induced Pulmonary Fibrosis Dec 2018 International Journal of Environmental
Research and Public Health 16(1):98 Follow journal DOI: 10.3390/ijerph16010098. Image from Vol-26, Number 9ā€”September 2020 Synopsis.
Figure 8: Ultrastructural- features of severe acute respiratory syndrome ā€“ SARS coronavirus 2 lung- infection in fatal coronavirus disease. A)
Top: alveolar space containing extracellular virions (arrows) with prominent surface projections. Bottom: cluster of virions in the alveolar- space (
A. S.) . Scale bars indicate 200 nm. B) Extracellular virions (arrow) associated with ciliated cells of the upper airway. Scale bar indicates 200 nm.
C) Membrane-bound vacuoles (arrows) containing viral- particles within the cytoplasm of an infected type II pneumocyte; surfactant (lamellated
-material) indicted by arrowheads. Scale bar indicates 1 Ī¼m. D) Membrane-bound vacuole (double-headed arrow in panel C) containing virus
-particles (arrows) with the characteristic black dots that are cross-sections through the viral nucleocapsid. Arrowheads indicate vacuolar-
membrane. Scale bar indicates 200 nm. E) Viral particles (arrow) within a phagosome of an alveolar macrophage. Scale bar: 200 nm. F) Viral
particles within a portion of a hyaline- membrane. Scale bar indicates 800 nm. Inset: Higher magniļ¬cation of virus- particles indicated by arrow;
scale bar indicates 200 nm. Image from Vol-26, Number 9ā€”September 2020 Synopsis.
COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work
https://www.heighpubs.org/hjcv 031
https://doi.org/10.29328/journal.ijcv.1001031
References
1. Ducatti A, Vargas VMF. Mutagenic activity of airborne particulate
matter as an indicative measure of atmospheric pollution. Mutat Res.
2003; 540: 67-77.
PubMed: https://pubmed.ncbi.nlm.nih.gov/12972059/
2. Erdinger L, DĆ¼rr M, Hƶpker KA. Correlations between mutagenic
activity of organic extracts of airborne particulate matter, NOx and
sulphur dioxide in southern Germany: results of a two-year study.
Environ Sci Pollut Res Int. 2005; 12: 10-20.
PubMed: https://pubmed.ncbi.nlm.nih.gov/15768736/
3. Inoue H, Fukunaga A, Okubo S. Mutagenic eļ¬€ects of nitrogen dioxide
combined with methylurea and ethylurea in Drosophila melanogaster.
Mutat Res. 1981; 88: 281-290.
PubMed: https://pubmed.ncbi.nlm.nih.gov/6789194/
4. Fukino H, Mimura S, Inoue K, Yamane Y. Mutagenicity of airborne
particles. Mutat Res. 1982; 102: 237-247.
PubMed: https://pubmed.ncbi.nlm.nih.gov/6755233/
5. Depayras S, Kondakova T, Heipieper HJ, Feuilloley MGJ, Orange N, et
al. The Hidden Face of Nitrogen Oxides Species: From Toxic Eļ¬€ects to
Potential Cure? Open access peer-reviewed chapter. 2018.
6. Chang J, Tao J, Xu C, Li Y, Li N, et al. Pollution characteristics of
ambient PM2.5ā€“bound benzo[a]pyrene and its cancer risks in Beijing.
Sci Total Environ. 209; 654: 735-741.
PubMed: https://pubmed.ncbi.nlm.nih.gov/30448664/
7. Remington KM, Bennett SE, Harris CM, Harris TM, Bebenek K. Highly
mutagenic bypass synthesis by T7 RNA polymerase of site-speciļ¬c
benzo[a]pyrene diol epoxide-adducted template DNA. J Biol Chem.
1998; 273: 13170-1316.
PubMed: https://pubmed.ncbi.nlm.nih.gov/9582358/
8. Luisetto M. Deforestation, air pollution and Brasisliant covid-19 variant.
Preprint Researchgate. 2021.

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Air pollution's role in COVID variants

  • 1. https://www.heighpubs.org/hjcv 022 https://doi.org/10.29328/journal.ijcv.1001031 Research Article COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work Luisetto M1 , Naseer Almukthar2 , Gamal Abdul Hamid3 , Tarro G4 , Khaled Edbey5 , Nili BA6 , Ghulam Rasool Mashori7 , Ahmed Yesvi Rafa8 and Latyshev O Yu9 1 IMA Marijnskaya Academy, Environmental Toxicology, Italy 2 Professor, Department of Physiology/College of Medicine University of Babylon, Iraq 3 Professor, Hematology Oncology, University of Aden, Aden, Yemen 4 President of the T & L de Beaumont Bonelli Foundation for Cancer Research, Naples Italy 5 Professor, Department of Chemistry, University of Benghazi, Libya 6 Innovative Pharmaceutical Product Development Specialist, USA 7 Full Professor of Pharmacology, Peoples University of Medical and Health Sciences for Women, Nawabshah, Pakistan 8 Founder and President, Yugen Research Organization, Western Michigan University, MI, USA 9 IMA Academy, President, Russian Federation More Information *Address for Correspondence: Luisetto M, IMA Marijnskaya Academy, Environmental Toxicology, 29121 Italy, Te: +393402479620; Email: maurolu65@gmail.com Submitted: February 06, 2021 Approved: February 15, 2021 Published: February 16, 2021 How to cite this article: Luisetto M, Almukthar N, Hamid GA, Tarro G, Edbey K, et al. COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work. Int J Clin Virol. 2021; 5: 022-031. DOI: 10.29328/journal.ijcv.1001031 Copyright: Ā© 2021 Luisetto M, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Keywords: Air pollution; Environmental toxicology; COVID-19 new variant; Mutagen; Particulate matter; No2; Benzo-a-pyrene; Cause- eļ¬€ect relationship; Direct or indirect actions OPEN ACCESS Introduction Coronaviruses are a group of related RNA- viruses that cause diseases in mammals and birds. They cause respiratory- tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the common cold (which is also caused by other viruses, predominantly like the rhinoviruses), while more lethal -varieties can cause SARS, MERS, and COVID-19 disease. The irst reports of a coronavirus- infection in animals occurred in the late 1920-1930 s, when an acute respiratory infection of domesticated chickens emerged in the North America. Abstract Before actual COVID-19 pandemia coronavirus was not so dangerous like now. In December 2019 - January 2020 in Wuhan ļ¬rst and then in other places this coronavirus was responsible of a ļ¬rst wave of severe pulmonitis responsible of many deaths. Wuhan and other region involved ļ¬rst was high level air polluted and industrial area. New COVID -19 variant in last part of 2020 and in ļ¬rst month of 2021 was responsible of great diļ¬€usion of this pandemic disease. UK, South Africa and brasilian new variant show higher diļ¬€usion then the ļ¬rst wave of COVID-19. Aim of this work is to analyze relationship with air pollution and the possibility that mutagen substantia inside of this microenvironment can produce new variant trough an genetic pressure process. RNA viruses are normally subjected by natural mutation but some phenomena can contribute to accelerate this process and their airborne ā€“ aeresols microenvironment is relevant. Some air pollutants are recognized as mutagen factors by literature.
  • 2. COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work https://www.heighpubs.org/hjcv 023 https://doi.org/10.29328/journal.ijcv.1001031 The virus was later known as an infectious bronchitis- virus (IBV). The most recent common ancestor of all coronaviruses is estimated to have existed as recently as about 8000 before common era, and some models back about 50 million years, this imply a long term coevolution with bat and avian species. Bats and birds, as warm-blooded lying vertebrates, are considered natural reservoir for the coronavirus gene pool. In last 2020 and in irst month of 2021 new COVID 19 VARIANT was responsible of great spread of the disease more higher then in the irst wave. Because relevant implication in public health politics it is really crucial to investigate some factor that can be considered to explain this phenomena. If RNA virus are involved in various kind of natural mutation process the relationship with some Polluted area and new variant explosion is interesting fact to be observed. South UK, Manaus ā€“ Brazil amazon zone and south Africa show a characteristic air pollution condition and the same it is interesting to observe that new variant emerged. (see researche article Deforestation, air pollution and Brasiliant COVID-19 variants Luisetto, et al. Jan 2021. Preprint Researchgate). Form CDC website New Variants of the Virus that Causes COVID-190 Updated Jan. 28, 2021 ā€œMultiple variants of the virus that causes COVID-19 are circulating globally: The United Kingdom (UK) identi ied a variant named B.1.1.7withalargenumberofmutationsinthefallof2020.This variant spreads more easily and quickly than other variants. In Jan. 2021, experts and researcher in the UK reported that this variant may be associated with an increased risk level of death compared to other variant viruses, but more research studies are needed to con irm this inding. It has since been detected in many countries around the world. This variant was irst detected in the US at the end of Dec. 2020. In South Africa S.A., another variant called B.1.351 emerged (Independently of the B.1.1.7). Originally detected in early October 2020, B.1.351 shares some mutations with B.1.1.7. Cases caused by this variant have been reported in the US at the end of Jan- 2021. In Brazil, a variant called P.1 emerged that was irst identi ied in travelers from Brazil country, who were tested during routine screening at an airport in Japan, in early Jan. This variant contains a set of additional mutations that may affect its ability to be recognized by antibodies. This variant was irst detected in the US at the end of January 2021ā€ And from WHO Coronavirus disease (COVID-19): Virus Evolution Dec. 2020. ā€œWhen a virus replicates or makes copies of itself, it sometimes changes a little bit. These changes are named ā€œmutations.ā€ A virus with one or several new mutations is referred to as a ā€œvariantā€ of the original virus. So the more viruses circulate, the more they may change. These changes can occasionally result in a virus variant that is better adapted to its environment compared to the original- virus. This process of changing and selection of successful variants is named ā€œvirus evolution.ā€ Some mutations can lead to changes in a virusā€™s characteristics, such as altered transmission (it may spread more easily) or severity (causing more severe- disease). Related velocity: Some viruses change quickly and others more slowly. SARS-CoV-2 tends to change more slowly than others such as HIV or in luenza viruses. This could in part be explained by the virusā€™s internal ā€œproofreading- mechanismā€ which can correct the ā€œmistakesā€ when it makes copies of itself. Scientists -and researcher continue to study this mechanism to better understand how it works.ā€ Genetic Variants of SARS-CoV-2ā€”What Do They Mean? Adam S. Lauring, et al: JAMA. Published online January 6, 2021. doi:10.1001/jama.2020.27124. ā€œOver the course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the scienti ic, and public health institutions have had to respond to new viral genetic- variants. Each one has triggered a lurry of the media attention, a range of reactions from the scienti ic community, and calls from governments to either ā€œstay calmā€ or pursue immediate- countermeasures. While many scientists were initially skeptical about the signi icance of the D614G alteration, the emergence of the new ā€œUK variantā€ā€” named lineage B.1.1.7ā€”has raised widespread concern. Understanding which variants are concerning, and why, requires an appreciation of virus- evolution and the genomic epidemiology of SARS-CoV-2. Mutations arise as a natural by- product of viral -replication. RNA- viruses typically have an higher mutation rates than the DNA viruses. Coronaviruses, make fewer mutations than most RNA- viruses because they encode an enzyme that corrects some of the errors made during replication. In most cases, the fate of a newly arising mutation is determined by natural -selection. Those that confer a competitive- advantage with respect to viral replication, transmission, or escape from immunity will increase in frequency, and those that reduce viral itness tend to be culled from the population of circulating- viruses. But mutations can also increase and decrease in frequency due to chance events.
  • 3. COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work https://www.heighpubs.org/hjcv 024 https://doi.org/10.29328/journal.ijcv.1001031 In example, a ā€œfounder effectā€ occurs when a limited number of individual viruses establish a new population during the transmission. The mutations present in the genomesoftheseviral-ancestorswilldominatethepopulation regardless of their effects on viral itness. This same interplay of natural- selection and chance events shapes virus evolution within hosts, in communities, and across countries. Although the terms mutation, variant, and strain are often used inter- changeably in describing the epidemiology of SARS-CoV-2, the distinctions are important. Mutation refers to the actual change in sequence: D614G is an aspartic acid-to-glycine substitution at position 614 of the spike- glycoprotein SPG. Genomes that differ in sequence are often named variants. This term is somewhat less precise because 2 variants can differ by 1 mutation or many. Strictly speaking, a variant is a strain when it has a demonstrably different phenotype (a difference in antigenicity, transmissibility, or virulence)ā€ (Fiures 1,2 ). The new -variant is correlated with a rapid increase in the COVID-19 incidence. This increase was reported in South- East England.Analysisusingviralgenome-sequencedataidenti ied a large proportion (> 49% - 50%) of cases that belonged to a new single lineage. Overall, around 5% to 10% of all COVID-19 cases are regularly sequenced in the UK. As of 26 Dec. 2020, about more than 3000 individuals had been identi ied with this virus variant in England, with the earliest case identi ied from 20 Sep. 2020. Several countries had reported sporadic- cases caused by the new variant from other EU/EEA countries (Belgium, Denmark, France, Germany, Iceland, Ireland, Italy, Netherlands, Norway, Portugal, Spain and Sweden) and globally (Australia, Canada, Hong -Kong, Israel, Japan, Jordan, Lebanon, South Korea, Switzerland, Singapore). South Africa S.A reported another SARS-CoV-2 variant of potential concern, designated 501.V2 that was irst observed in samples from Oct. and since then evolved to be the dominant circulating variant in South Africa (From LNS). FIG. N 3. FROM By Dr. Liji Thomas, MD 2020 SARS-CoV-2 genome variants in India. ā€œMapping of higher frequency amino acid mutations on Nucleo-capsid and Spike proteins. The mutations are marked in red color on the surface representation of each protein. In the Spike protein, all the domains are highlighted in different colors, including NTD, RBD, HR1, Fusion peptide region, HR2, TM, and CT domains. The cleavage sites are also marked onto the structure Mutations and Protein Effects: The investigators also looked at the mutant- proteins Figure 1: A - Phylogenetic tree: showing the relationship of lineage B.1.1.7 (20B/501Y.V1, orange branch and tips) to other circulating- lineages. The long branch length for this lineage reļ¬‚ects the fact that it accumulated a signiļ¬cant number of mutations prior to being discovered. B, Frequencies of circulating lineages over the time. Lineages are colored as in the tree, with lineage B.1.1.7 (20B/501Y.V1) shown in orange (From JAMA).
  • 4. COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work https://www.heighpubs.org/hjcv 025 https://doi.org/10.29328/journal.ijcv.1001031 expressed as a result of amino- acid AA substitutions across the 104 genomes. There were 53 point of mutations, of which 29 resulted in missense- mutationsā€ (Liji Thomas). When studied in relation to the proteins affected, the scientists found that most variations were in non-structural protein (nsp) 6, in 68 genomes, with nsp 12 in 65, nsp 3 in 62, and P13L, a nucleocapsid protein, in 53. One of the commonly found worldwide- mutations, D614G, in spike- protein, was found in only 26 genomes. The researchers and scientist then followed the frequency of mutation with respect to the type of change in the amino- acid AA. They found that in about 44%, the amino acid was not changed, which indicates that perhaps the mutation caused a slight- change in the shape or function of the protein. The same thing was observed with very frequently found mutations, like as P13L. In some other kid of mutations, the type of amino acid AA was quite different, with a hydrophobic-to-polar or charged type of alteration. One example is that of the addition of a charged residue to the frequently mutated position T1198K in nsp3, or the loss of a charged- group with the important spike- protein SPM- mutation D614G. Such a changeover to a residue with a positive- charge may possibly result in more signi icant effects on the structure and function of the protein involved. (From By Dr. Liji Thomas, MD 2020 SARS-CoV-2 genome variants in India). Material and methods With an observational and visual method a literature search was performed in biomedical database. Some relevant igure are presented to better explain the meaning of this work. An experimental hypothesis is submitted in order to verify what fended in literature research. After this phases a global conclusion is submitted to the researcher to be more veri ied in larger scale. Figure 2: A new SARS-CoV-2 variant referred to as SARS-CoV-2 VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01), has been declared by the British -authorities. The variant was detected via genomic- sequencing in the UK. It is deļ¬ned by multiple spike protein mutations (deletion 69-70, deletion 144, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H) present.
  • 5. COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work https://www.heighpubs.org/hjcv 026 https://doi.org/10.29328/journal.ijcv.1001031 Results From literature According A Ducatti, et al: ā€œMutagenic activity of organic- extracts of airborne particulate matter- PM at four different sites within the urban area of the city of Porto- Alegre, Brazil, was investigated using the Salmonella/microsome assay, with the Kado micro-suspension method. The extracts were obtained by sonication, sequentially extracted according to polarity, with cyclohexane (CX) and dichloromethane (DCM) solvents. The different fractions were tested for mutagenicity with the Salmonella typhimurium strains TA98, TA98NR and TA98/1,8-DNP6, without S9 mix metabolic activation. A positive (+) frameshift mutagenic response was observed for non-polar (CX) and/or moderately polar (DCM) compounds at the different sites. The responses varied at different year seasons, and the highest revertants per m3 (rev/m3) values were observed at the site subject to the strongest in luence of automotive- vehicles (site 3) in spring (17.13 rev/m3) in DCM fractions, and in summer (13.01 rev/m3) in CX fractions. The responses observed for the TA98NR and TA98/1,8-DNP6 strains suggest the contribution of nitro-compounds to the mutagenic activity observed. Although there appears to be an indicative association between the increased mass per unit volume of air (TSP) and the mutagenicity of organic- extracts of airborne particulate matter in the present study, the Salmonella/microsome assay was a sensitive method to de ine areas contaminated by genotoxic- compounds, even in samples that present TPS values acceptable by the environmental- quality standards established by lawā€[1]. Erdinger L, et al: ā€œAmong other substances, sulphur dioxide (SO2 ), nitric oxide (NO) and nitrogen dioxide (NO2) are parameters which are routinely measured to describe the basic air -quality. Organic extracts of airborne particulate matter PM contain mutagenic chemical compounds of different origins. The aim of the study was to ind correlations between routine- monitoring data and mutagenic activity of organic extracts of simultaneously drawn samples. Specimens were collected over a period of 2 years at 8 sampling sites in south-west Germany. Simultaneously, concentrations of NO, NO2 , and SO2 were measured on-line within the framework of the of icial air monitoring network of Baden-WĆ¼rttemberg, Germany. Dust samples were collected for biotesting using high volume air -samplers equipped with glass ibre ilters. After sampling was completed, ilters were extracted and samples were prepared for biological testing. Mutagenic activity was tested by means of the plate incorporation assay (Ames test) using S. typhimurium TA98 and TA100 tester strains. During the irst year of the study, all tests have been performed with and without metabolic- activation. A series of tests has been performed in parallel with TA98 and TA98NR. Comparison of Ames- test data obtained with and without metabolic- activation indicates no statistically signi icant difference between the both methods. During the second year of the study, all tests have been performed without metabolic activation. Average- yearly activities at the sampling sites were between 1 and 27 Revertants per m3 (Rev/m3). High -activities were preferably found at congested sites (Karlsruhe, up to 95 Rev/m3). Peak values of over 100 Rev/ m3 were found in other places where pollution by traf ic is signi icantlylower.Thereasonforthesehighlevelvaluesisnot evident. Tests performed using TA98NR tester strain indicate a signi icant share (average 31%) of compounds requiring activation by nitro-reductase for mutagenic activity. Average mutagenic- activity can be correlated to routine monitoring parameters. Comparison of averaged data for particular sampling sites indicates signi icant correlation between nitric- oxide and mutagenic activity in TA98 (r2 = 0.90), while correlation between nitrogen dioxide (0.84) or sulphur dioxide (0.52) and mutagenic -activity is weaker. For TA100, correlations are generally weaker than for TA98. Comparison of data for mutagenic activity and routine monitoring data of distant sites being sampled simultaneously shows parallel- behaviour.Results from this study show that mutagenic- activity can be compared to seasonal and local variations of gaseous indicator air pollutants. Tester strain TA98 generally shows the best correlations. Although pollution by particle- bound mutagenic substances is signi icantly higher during the cold -season than during summer on average, mutagenic- activity of airborne dust is not a continuous effect. During winter, peak levels as well as low pollution periods can occur. Even during winter time mutagenic activity can reach very low- levels typical for summer-time. Comparison of results for distant sampling sites where samples have been collected simultaneously indicate that ā€˜classicalā€™ indicators of air- pollution and bacterial mutagenicity of organic- extracts from airborne particulate matter are in luenced by connected effects. Seasonal trend of mutagenic activity, in particular, is similar to the concentrations of nitrogen- oxide. NO is a strong indicator for vehicle exhaust gases. It is concluded that the average mutagenic- activity at particular sites can be estimated using NO- concentrations as an indicatorā€ [2]. ā€œThe standard sex-linked recessive lethal test was used to test whether NO2 induces lethal- mutations in male germ- cells of Drosophila in the presence or absence of alkylureas. Methylurea, ethylurea and NO2 alone did not enhance the mutation frequency signi icantly. Highly signi icant enhancement in mutation frequency was observed when adult lies were exposed to NO2 (150 - 280 ppm) for 3 h after ingestion of methylurea (0.1 M) or ethylurea (0.1 M) for 2 days. Oral- administration of ethylnitrosourea and also of methylurea or ethylurea that had been exposed to NO2 in vitro were more effective in increasing the mutation frequency than methylurea or ethylurea combined in vivo with NO2 . These results suggest that ingested alkylurea is converted in vivo
  • 6. COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work https://www.heighpubs.org/hjcv 027 https://doi.org/10.29328/journal.ijcv.1001031 by inhaled- NO2 to highly mutagenic nitrosoalkylurea and/or other mutagens. No signi icant enhancement of the mutation- frequency was observed when lies were fed on methylurea solution after they had been exposed to NO2 ā€ [3]. Mutat Res Oct-Nov 1982 Mutagenicity of airborne particles H Fukino, S Mimura, K Inoue, Y Yamane ā€œThe mutagenicity of airborne- particles was studied in the Ames Salmonella -system. The mutagenic activity of benzene extracts from airborne- particles was more active in strain TA98 in the presence and absence of S9 mix than in strain TA100. The presence of mutagens, other than benzo[a]pyrene (B[a]P), which did not require S9 mix, was indicated. The monthlyvariationofdirect-actingmutagenicactivityshoweda pattern similar to that of B[a]P at atmospheric- concentration. The monthly variations of atmospheric NO, NO2 , NO-2 and NO-3 concentrations were also similar to that of the direct- acting mutagenic- activity. Atmospheric concentrations of heavy metals such as Pb, Zn, Cd, V and Cu were also found to be related to direct-acting mutagenic activity. These results suggest that emissions from automobiles, home heaters and power plants and so on. May be a primary source of atmospheric, direct-acting mutagens. It is suggested that secondary direct-acting mutagens might be partly formed by the nitration of polycyclic- aromatic hydrocarbons (PAH) with NO2 in the atmosphere because concentrations of B[a]P, NO2 and NO-3 increased simultaneously when the highest direct- acting mutagenic activity was observedā€ [4]. Yet, pollution is the largest environmental cause of disease and death in the world today, responsible for an estimated about 9 million premature deathsā€ stated The Lancet Commission in 2017. This phenomenon represents an alarming- threat for human health, as a major cause of respiratory and cardiovascular CV pathologies as well as infertility. Those atmospheric pollutants have severe impacts on the environment and participate in climatic change, acidi ication, eutrophication, and ecosystem disturbances. Several international and national organizations (WHO, EEA, and INERIS) aim at reducing the global emission of pollutants, thanks to environmental policies as Kyoto and Gothenburg protocols signed in 1997 and 1999, respectively. After that, an encouraging decrease in air pollutantsā€™ levels was measured between 2000 and 2015. Atmospheric- pollutants can be classi ied into four families: classical, indoor, and organic or inorganic air pollutants. Among the classical ones, which are the principle in amount, sulfur dioxide (SO2 ), particle matter, ozone (O3), and nitrogen oxide (NOx) species are found. The term NOx refers to a wide range of nitrogen-derived compounds, where nitric oxide (NO) and nitrogen dioxide (NO2 ) are predominant. Those compounds can be naturally produced at low level by lightnings [4] and volcanic eruptions. NOx is mainly generated by anthropogenic activity (road transport, energy production, industry, and agriculture. NO and NO2 , thanks to their chemistry properties mentioned earlier, are highly diffusible through living membranes and exhibit a strong reactivity [5]. Related eļ¬€ect of air pollution by benzo -a- pirene ā€œThe purpose of this research study was to reveal the pollution characteristics of ambient PM2.5ā€“bound benzo[a] pyrene (B[a]P) in Beijing and to assess the lifetime cancer- risk from respiratory pathway exposure. The average daily dose was evaluated by the annual concentrations of ambient PM2.5ā€“bound B[a]P, combined with Chinese human exposure factors and the age sensitivity factors. The 70-year lifetime cancer risks of different groups were assessed by the exposure assessment and stochastic analysis -method recommended by California Environmental Protection Agency CEPA. The groups were divided by age and gender. The results showed that the ambient PM2.5ā€“bound B[a]P concentration during the cold season was 15.7 times greater than that during the warm season in Beijing. The annual -average concentrations of PM2.5ā€“bound B[a]P in outdoors and indoors were 1.67ā€Æng/ m3 and 1.04ā€Æng/m3, respectively, which exceeded the limit of Chinese National Ambient Air- Quality Standard. The cancer- risks of PM2.5ā€“bound B[a]P in males, females, and the general -population were 9.085ā€ÆƗā€Æ10āˆ’6, 8.050ā€ÆƗā€Æ10āˆ’6, and 8.740ā€ÆƗā€Æ10āˆ’6, respectively. The cancer- risk constituent ratios of ambient PM2.5ā€“bound B[a]P in early life (ā‰¤16ā€Æyears of age) for males, females, and the general population were 70.9%, 71.4%, and 71.3%, respectively. The malesā€™ cancer risk of PM2.5ā€“bound B[a]P in Beijing was higher than that of the females. The early- life cancer risk exposure to PM2.5ā€“bound B[a]P should be paid more attentionā€ [6]. Remington KM, et al: in article ā€œHighly mutagenic bypass synthesis by T7 RNA polymerase of site-speci ic benzo[a] pyrene diol epoxide-adducted template DNAā€. ā€œWe have previously developed an in vitro- system IVS that allows quantitative evaluation of the idelity of transcription during synthesis on a natural template in the presence of all four nucleotides. We have employed this system using a TAA ochre codon reversion- assay to examine the idelity of transcription by T7 RNA polymerase past an adenine residue adducted at the N6-position with (-)-anti-trans- or (+)-anti- trans-benzo[a]pyrene diol epoxide (BPDE). T7 RNAP was capable of transcribing past either BPDE isomer to generate full-length run-off transcripts. The extent of bypass was found to be 32% for the (-)-anti-trans-isomer and 18% for the (+)-anti-trans-isomer. Transcription past both adducts was highly- mutagenic. The reversion frequency of bypass synthesis of the (-)-anti-trans-isomer was elevated 11,000- fold and that of the (+)-anti-trans-isomer 6000-fold, relative to the reversion frequency of transcription on uneducated- template. Adenine was misinserted preferentially, followed by guanine, opposite the adenine adducted with either BPDE isomer. Although base substitution errors were by far the
  • 7. COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work https://www.heighpubs.org/hjcv 028 https://doi.org/10.29328/journal.ijcv.1001031 Figure 3: From By Dr. Liji Thomas, MD 2020 SARS-CoV-2 genome variants in India. Figure 4: eļ¬€ect of No2.
  • 8. COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work https://www.heighpubs.org/hjcv 029 https://doi.org/10.29328/journal.ijcv.1001031 most frequent mutation on the adducted template, three- and six-base deletions were also observed. These results suggest that transcriptional errors, particularly with regard to damage bypass, may contribute to the mutational- burden of the cell.ā€ [7]. Experimental hypotesys project In order to verify the effects of someaereosol microenvironment it is possible to think to observe effect in various vials containing in equal way: Particulate matter, benzo- a pyrene and other air pollutant in an antmosphere rich in NO2 (and like very polluted industrial city examples). Different vial containings in separated way Animal cells; Bacterial cells; Virus DNA particles, Virus RNA particle. (Plus eucaritota cell or not to verify effect of RNA virus translation). Time of exposition: from 30 days to 6 month. Other condition: various level of humidity and ozone, and under different level of sun light irradiation (but also in similar way like the sun light in a ozone layer loss region), lightning or not. After this sample experiment the data must be collected and statistically analyzed to verify level of mutation of genetic materials. Discussion From literature observed many mutation are observed in COVID-19 this involved nucleocapside and spike protein) and this are responsible in increased transmission and severity level of the disease. Spontaneous phenomena are responsible in many RNA virus evolution and also by environmental pressure. But it is interesting to observe that some air pollutants like NO2 and particulate matter (and carried substatie like benzo- a-pyrene) can produce a mutagen micro-environment that can contribute in emerging of new variants. Mutagens that can act also as indirect factor (involving a eucariote translation of information). In some current decontamination sterilization procedure are used UV ray that with a physical way produced irreversible damages to genetic materials of bacteria and virus so it is possible to consider that mutant agent that currently produces damages in human cells ( and cell death) they can produce damages also in Rna -virus. So it is possible to submit to the researcher the conclusion that an airborne microenvironment with mutagen agent inside can produce new variants also in some RNA -virus expression in higher way vs. without mutagen agent presence (direct or in indirect way). It must to be considered the complex of RNA virus, Particulate matter covered with mutagen susbtantie and pulmonary cell infected involved in virus reproduction -replication (Figures 7,8). Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States Roosecelis B Martines, et al: Finally: Relevant for this phenomena are: time of exposition, kind of mutagen molecule, carriers, aeresols microenviroment, direct or indirect damage, reversible or irreversible action, ef iciency of variant in virus survivor and in transmission. Conclusion Observing the literature reported a conclusion can be submitted to the researcher: As hypothesis of work it is crucial to investigate the role played by some air pollutant in some world region in produce genetic modi ication and select respiratory virus new variant. Before actual pandemia coronavirus was not so dangerous like COVID-19. A real fact that this virus spread form really polluted area like WU-HAN or other world region like. North Italy and that new variant was observed in South UK, MANAUS, South Africa. Ethical consideration: All ethical rules respected. Figure 5: Khaya senegalensis Seeds. Figure 6: benzo ā€“ a- pirene.
  • 9. COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work https://www.heighpubs.org/hjcv 030 https://doi.org/10.29328/journal.ijcv.1001031 Figure 7: PM2.5 exposure induces pulmonary- inļ¬‚ammation and ļ¬brosis. (A) Lung sections from ļ¬ltered -air (FA) and particulate matter (PM2.5)-exposed mice were stained with hematoxylin and eosin (H&E) and Sirius red staining at 200Ɨ magniļ¬cation. (B-E) After exposure for 12 weeks, the mRNA- levels of ļ¬brotic- genes collagen I and transforming growth factor Ī² (TGF-Ī²) in lungs (B, C) and the level of inļ¬‚ammatory factors- interleukin 6 (IL-6) and tumor necrosis- factor Ī± (TNF-Ī±) in serum (D, E) were measured by qPCR and enzyme linked immunosorbent- assay (ELISA) kits, respectively. Data are presented as mean Ā± standard deviation (SD); *p < 0.05, **p < 0.01 vs. FA group. Form TMT- Based Quantitative Proteomics Analysis Reveals Airborne PM2.5-Induced Pulmonary Fibrosis Dec 2018 International Journal of Environmental Research and Public Health 16(1):98 Follow journal DOI: 10.3390/ijerph16010098. Image from Vol-26, Number 9ā€”September 2020 Synopsis. Figure 8: Ultrastructural- features of severe acute respiratory syndrome ā€“ SARS coronavirus 2 lung- infection in fatal coronavirus disease. A) Top: alveolar space containing extracellular virions (arrows) with prominent surface projections. Bottom: cluster of virions in the alveolar- space ( A. S.) . Scale bars indicate 200 nm. B) Extracellular virions (arrow) associated with ciliated cells of the upper airway. Scale bar indicates 200 nm. C) Membrane-bound vacuoles (arrows) containing viral- particles within the cytoplasm of an infected type II pneumocyte; surfactant (lamellated -material) indicted by arrowheads. Scale bar indicates 1 Ī¼m. D) Membrane-bound vacuole (double-headed arrow in panel C) containing virus -particles (arrows) with the characteristic black dots that are cross-sections through the viral nucleocapsid. Arrowheads indicate vacuolar- membrane. Scale bar indicates 200 nm. E) Viral particles (arrow) within a phagosome of an alveolar macrophage. Scale bar: 200 nm. F) Viral particles within a portion of a hyaline- membrane. Scale bar indicates 800 nm. Inset: Higher magniļ¬cation of virus- particles indicated by arrow; scale bar indicates 200 nm. Image from Vol-26, Number 9ā€”September 2020 Synopsis.
  • 10. COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work https://www.heighpubs.org/hjcv 031 https://doi.org/10.29328/journal.ijcv.1001031 References 1. Ducatti A, Vargas VMF. Mutagenic activity of airborne particulate matter as an indicative measure of atmospheric pollution. Mutat Res. 2003; 540: 67-77. PubMed: https://pubmed.ncbi.nlm.nih.gov/12972059/ 2. Erdinger L, DĆ¼rr M, Hƶpker KA. Correlations between mutagenic activity of organic extracts of airborne particulate matter, NOx and sulphur dioxide in southern Germany: results of a two-year study. Environ Sci Pollut Res Int. 2005; 12: 10-20. PubMed: https://pubmed.ncbi.nlm.nih.gov/15768736/ 3. Inoue H, Fukunaga A, Okubo S. Mutagenic eļ¬€ects of nitrogen dioxide combined with methylurea and ethylurea in Drosophila melanogaster. Mutat Res. 1981; 88: 281-290. PubMed: https://pubmed.ncbi.nlm.nih.gov/6789194/ 4. Fukino H, Mimura S, Inoue K, Yamane Y. Mutagenicity of airborne particles. Mutat Res. 1982; 102: 237-247. PubMed: https://pubmed.ncbi.nlm.nih.gov/6755233/ 5. Depayras S, Kondakova T, Heipieper HJ, Feuilloley MGJ, Orange N, et al. The Hidden Face of Nitrogen Oxides Species: From Toxic Eļ¬€ects to Potential Cure? Open access peer-reviewed chapter. 2018. 6. Chang J, Tao J, Xu C, Li Y, Li N, et al. Pollution characteristics of ambient PM2.5ā€“bound benzo[a]pyrene and its cancer risks in Beijing. Sci Total Environ. 209; 654: 735-741. PubMed: https://pubmed.ncbi.nlm.nih.gov/30448664/ 7. Remington KM, Bennett SE, Harris CM, Harris TM, Bebenek K. Highly mutagenic bypass synthesis by T7 RNA polymerase of site-speciļ¬c benzo[a]pyrene diol epoxide-adducted template DNA. J Biol Chem. 1998; 273: 13170-1316. PubMed: https://pubmed.ncbi.nlm.nih.gov/9582358/ 8. Luisetto M. Deforestation, air pollution and Brasisliant covid-19 variant. Preprint Researchgate. 2021.