Impact of SARS CoV-2 Variants' Mutation on Pathogenicity, Diagnosis and Vaccine

This research aims to determine the impact of SARS CoV-2 variants' mutation on pathogenicity, diagnosis and vaccine. It includes phylogenetic analysis of structural proteins, multiple sequence analysis, and analysis of vaccine efficacy. The study also explores the impact of mutation on pathogenicity, epidemiology, and diagnosis. The research is significant in understanding the implications of SARS CoV-2 variants and developing effective strategies to combat the virus.

CORONAVIRUS

ACKNOWLEDGEMENT
In this, I want to show my gratitude and also express my thanks to professor as well as to
my teacher and other lecturer who provide me this golden opportunity and also, they help me
with every angle by giving their time for assisting me in this research. I am really thankful to my
teacher and my friend who supported me with every dimension in this specific topic.

ABSTRACT
As per this, the particular research topic is about the recent ongoing issue which change
the paradigm of the worldwide. This issue is biological in nature and named is coronavirus. This
is also known as the COVID-19. In this, the corona virus uses to change the dimension of world.
Now a day, this virus is more population collecting criteria and this virus infect up to maximum
people and formulate the condition of threat. This virus is called as deadly virus. As per this, this
virus has their history and background that cause number of situations in past. Their pathogen-
city is a vital factor which is create number of issues related with health. This virus is originated
in 2019 and they called as COVID-19. There are number of factor and their pathophysiology
alter the physiology of human body and create the situations of illness. This virus is
communicable in nature and they have high rate of spread rate. In this, there variability and their
variant are discussed with their pathogen-city, diagnose and their vaccination process.

Table of Contents
ACKNOWLEDGEMENT...............................................................................................................2
ABSTRACT.....................................................................................................................................3
INTRODUCTION...........................................................................................................................1
RESEARCH AIM............................................................................................................................2
RESEARCH OBJECTIVE..............................................................................................................3
RESEARCH QUESTION................................................................................................................3
RATIONALE OF THE RESEARCH..............................................................................................3
SIGNIFICANCE OF THE RESEARCH.........................................................................................4
SUMMARY OF THE CHAPTER...................................................................................................4
LITERATURE REVIEW................................................................................................................5
Phylogenetic analysis of the four various types of structural protein (Spike, Membrane,
Envelope, and Nucleocapsid).................................................................................................5
The multiple sequence analysis of the proteins......................................................................6
The effect and impact of the variance mutation on vaccine efficacy.....................................8
Impact of the mutation on pathogen-city, epidemiology and diagnosis.................................9
Factors affecting the efficacy of vaccine..............................................................................11
Structural difference between variant protein (S, E, M & N)..............................................13
Structure of E protein...........................................................................................................14
Structure of M protein..........................................................................................................15
Structure of N protein...........................................................................................................15
RESEARCH METHODOLOGY...................................................................................................16
RESULTS......................................................................................................................................19
FINDING, DISCUSSION AND CONCLUSION.........................................................................23
REFERENCES..............................................................................................................................26

INTRODUCTION
In this, the SARS is defined as the severe acute respiratory syndrome which is caused by
the factor which is associated with the coronavirus. This is being well identified that this disease
is usually caused by number of factors. In this, the SARS is an airborne disease which is
communicable in nature and they are transferred from one individual to other by the water
droplet or small droplet of saliva in the similar way to the cold and influenza. This all are the first
severe and this can readily transmissible in the aspect of new disease to emerge in the current
time (Balasubramanian and et. al., 2020). They have clear capacity to spread to the number of
people along with the international air travel and this can gather maximum number of infections
by their virus. As per this, the number of patients is identified as the SARS which is previously
for the health adults age 25 year to 70 years. The case of fatality among person with the proper
illness which is define the case definition for the condition and suspected case of SARS is in
around 3 percent. The SARS is usually having number of variants which is identified in
numerous years. This all started with a specific country and after that they came at the point of
pandemic. This is also stated that the SARS is a viral respiratory disease which is originated
from the zoonotic origin caused by the severe acute respiratory syndrome coronavirus. This is
also mentioned like SARS-CoV or SARS-CoV-1. The first identified strain which is provide the
SARS for the coronavirus species such as severe acute respiratory syndrome which is related
with the coronavirus. This syndrome is usually caused the 2002-2004 which is based on the
severe acute respiratory syndrome. As per previous identified research this is well analyse that
there is various Chinese scientist traced the virus which help me to go through the intermediary
of the Asian palm civets which is usually determined the horseshoe bat in the town of Yunnan
(Clancy and et. al., 2020).
There are number of variants which is used to follow the various number of sequences.
As per this, they are used to create various enormous function in body. Such as the whole virus
which is used to replicate including the factor of SARS-CoV-2. In context with this, they take
time of evolve. When a virus replicates or make copies of itself. Then it will create number of
factors such as they use to choose the copies of itself. It sometime changes the factor of covid in
the ratio of normal bit. These kinds of factor are used to cause the mutation. There are number of
new and more mutant. The mutation is referred as the variant of the original virus. As per this
they follow sequence of the variant in the different countries. This kind of the changes are
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undergoing and create a rapid mutation and formulate various form of covid. In this, most of the
viral mutation have a little to no impact on the virus ability to cause various number of infections
which is used to formulate disease. This all aspect is depending on the various changes. This all
study is held under taking the aspect of UK, Brazil and South Africa (Fioranelli and et. al.,
2020).
In another aspect, in December 2019 there is another kind of strain which is well
identified as the severe acute respiratory syndrome which is coronavirus 2 called as SARS-CoV-
2. As per this, the new strain causes to the coronavirus disease which is established with the
2019. There is various disease which is brought about the pandemic of the COVID-19. As per
this, there are various number of factors which is associated with this. The primary route of
transmission for the SARS-CoV is the contact of the membrane of mucus membrane with the
factor with respiratory droplets or fomites (Han and et. al., 2020). In this context, the diarrhoea is
common with the people with the SARS with mode of faecal route. They do not be common
mode of appear in order to create the transmission. There are various basic chapter of the
reproduction number of SARS-CoV, Ro which is lies in the range of from 2 to 4 which is used to
depend on the various number of analysis (He and et. al., 2020). This all-control measure which
is introduced in order to reduce the in the April 2003 and this lies in the range of R to 0.4. The
virus that caused the COVID-19 is the variant of the SARS family. As doing comparison from
other this is identified as the recent virus us more transmissible than the wild type of SARS-
CoV-2and this was detected and came in the origin at November 2020. This is started to the
begin with quickly by spreading by mid-December and this all are corrected with the significant
enhancement in the SARS. This is all increase is the process of through which has to be partly
because of one and more. This all are mutational in nature. As per this, the virus used to grow
through the spike protein. This type of variant is not notable for having the more alteration in the
gene and the DNA of the virus and they change their DNA and turn themselves into the deadlier
virus (Khan and et. al., 2020). As per this, they are used to take various protein in this to form
various course of action. In this, the surface protein, membrane protein, and envelope protein and
nucleocapsid protein are used to understand the topic of coronavirus. This all variants which
show the upcoming nature that may be from the various such as UK and Brazil and so on.
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RESEARCH AIM
To determine the impact of SARS CoV-2 variants’ mutation on pathogenicity, diagnosis
and vaccine.
RESEARCH OBJECTIVE
 To perform the phylogenetic analysis of the four various types of structural protein
(Spike, Membrane, Envelope, and Nucleocapsid).
 To perform the multiple sequence analysis of the proteins.
 To determine the effect and impact of variance mutation on vaccine efficacy.
 To compare the impact of mutation on pathogenicity, epidemiology, and diagnosis.
 Analyse how some mutations affect the efficacy of the vaccine.
 Analyse the structural difference between the variants’ proteins (S, E, M & N).
RESEARCH QUESTION
 What are the phylogenetic analysis of the four various types of structural protein (Spike,
Membrane, Envelope, and Nucleocapsid)?
 What are the multiple sequence analysis of the proteins?
 What are the effect and impact of variance mutation on vaccine efficacy?
 What are the impact of mutation on pathogenicity, epidemiology, and diagnosis?
 How some mutations affect the efficacy of the vaccine?
 What are the structural difference between the variants’ proteins (S, E, M & N)?
RATIONALE OF THE RESEARCH
In this, the main theme is to choosing this topic is to examine and evaluate the various
cause and outcome. There are number of factors which is associated with the topic. As per this,
the topic state about the various scenario of coronavirus and this help to know their implications.
This topic is help to study about the phylogenetic analysis of the four various types of structural
protein (Spike, Membrane, Envelope, and Nucleocapsid) and in this it helps analyse the multiple
protein. As per this, the overall study helps to evaluate the measurement which is related with the
personal and professional growth and development. There are number of view point which is
helpful in this. Some of the expert share their view due the recent factor which create various
hindrance in the system of living and the pattern of life. They have number of variants which
show progress growth in their unit. Moreover, some the analysis which is relatable in this are
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their various mutant which is growing now day and may affect a huge population. Usually, their
other species is also show the crown like structure and inhibit the other approach which is
tremendous and have ability to control. However, the study of the various mutant of coronavirus
uplift the knowledge and skill. This help in the development of sound professional career and in
the aspect of future long perspective along with this code of effectiveness which help in other
ways to cope in find productive loop. This can create the sense of process and their limitation
and help to create the matter of various issue. In this, the proper aspect which is help to
determine the issue and eradicate this by using the proper analysis of problem.
SIGNIFICANCE OF THE RESEARCH
In this, there are number of factors which is associated with this and cause various issue
which associated with this topic. This research indicates various of outline and outlook for the
causes and their majority of theme. The effect and impact of the variance mutation on the
vaccine and their efficacy are well discussing. This is some of the objective in which the research
is conducted. Usually, this research helps to identify various impact and effect which is studied
and analyse the way by measuring the mutation on their pathogenicity, epidemiology and
diagnosis. This all study used to provide effective knowledge and skill about the topic and this
approach is helpful for the researching about the theme and aim. The main importance of this
research is to provide the knowledge which is related with the topic. As per this, there are
various of determinants of the relevant point in order the possible ways to reduce the proper rate
of impact and their phylogenetic structure which is help to know the structure protein which is
called as spike protein membrane, envelop and nucleocapsid. Some the factor which is essential
in this are study about the variant of protein which show the numeric data their impact in other
population.
SUMMARY OF THE CHAPTER
This topic state about the various aspect of coronavirus such as it states about the number
of phylogenetic structures of the different type of structural protein which is spike membrane,
envelop and also a sensitive protein which is defined as the nucleocapsid. In this, the summarised
way which is show the condition such as it is used to create the sequence which is useful in the
analysis of protein. In this, they are used to know the other segment of factor which is stated and
overviews. In this, the evaluation is based on the effect and impact of the variance which help to
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build to the mutation on the effectively. There are number of mutational techniques which help
to follow the pathogenicity which is help in the epidemiology, and help in the diagnosis. While
communicating with this, they used to create proper vaccine which is important for their various
variant. As per this, the affectivity of the vaccine which may be decreased due to this. In this
section of work, the structural and combinational differences are allowed in ways which help to
put the diversification in number of variant proteins. So, the overall coronavirus is studied as per
base of their protein and other aspect of vaccination while formulating and what are the other
factor which is associated with this. This research is conducted over a year or many numbers of
time zone. This also provide proper control behaviour to manage the flow of protein.
LITERATURE REVIEW
Phylogenetic analysis of the four various types of structural protein (Spike, Membrane,
Envelope, and Nucleocapsid)
The phylogeneticity is defined as the development and diversification of a species which
has proper group of organisms and they are used to provide the feature of an organism. In this
scenario this all aspect is based on the protein which have significant structure and they have
proper trait and method. The nomenclature of the protein is based on their species and their
nature. As per this, the causative agent which is well determined as a novel RNA virus of the
family which is stated as the coronviridae and this is subsequently designated as the SARS-CoV-
2. This all are high level of protein. This is helpful in the factor of outbreak which is severe acute
respiratory syndrome which is extend between the human which is associated with the 2002 and
2004. In this, the previous studies are used to analyse the SARS-CoV-2 genome which is helpful
in the human between 2002 and 2004. This all aspect is used to made the epidemic and estimated
at the time of early month. This is in order to make a hypothesis which is used to show the
SARS-CoV-2 which may undergone on a period of cryptic transmission is asymptomatic or
mildly symptomatic which is caused as the unit and identified the cluster report. SARS-CoV-2
has spread which is throughout the world in this there are ongoing pandemic. As per this, the
SARS-CoV-2 which is associated with the Beta coronavirus belonging from the coronaviridae
family. In this, the coronavirus is enveloped in the positive sense which is associated with RNA
virus with the large factor and create the non-segmented genome. This all include the five major
open reading frame such as ORF1a, ORF1ab and these all four structural proteins which is
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associated with the plus a number of accessory gene. The first two overlapping ORFs which is
located at the end of 5' prime. In this, there are various viral RNA are involved which is used to
occupy about the third of the genome and encode the protein which are autoproteolytically
processed which is comes under the section of 16 non-structural proteins. There are number of
interactions among the several SARS-CoV-2 which is used to define the non-RNA replication
and transcription. In this, the number of interactions is used and show the approach which is
related with the RNA replication and transcription. The human interaction which is accessible
among the SARS-CoV-2 which show the non-structural and combination of human protein. The
third end point which is fragile in nature and show 3 prime factors from the genome which is
viral in nature that encode the major component show the structural protein such as spike,
envelope, membrane and nucleocapsid. That all are required for the structure base scenario in the
viral particle. The coronavirus which is associated with S protein which is trimeric glycoprotein
which that is belong to the class one fusion of test. This allow to viral entry by attaching the S1
subunit which is associated with the host cell receptor that is angiotensin converting enzyme two.
By this segment the S1 receptor binding domain. This all process requires the factor of S protein
which show the function of priming by host proteases such bas TMPRSS2 in the form of rupture
site such as S1/S2 which show the data of poly basic such as motif at the S1 and S2 boundary.
The E protein which is less abundant protein which show the essential assembly and as per this
there are various interaction with the M protein. This all protein is associated with the critical
aspect of the viral life cycle and this lacking the e protein. Some of the make promising vaccine
for the candidate. As per this, they are used to show the effect which is ordinary in nature and
this all variant are used show the numerous of factor that is associated with the spike protein and
this is originated from the UK.
The multiple sequence analysis of the proteins
There are number of multiple sequence alignment called as MSA which is defined as the
method which is refer for the solution of alignment which is related to the sequences. As per this,
they are used to taking the account which is evolutionary events such as mutation, insertion,
deletion and rearrangement which is comes under the certain condition. These methods are used
in such a way which is usually applied to show the faith of DNA, RNA or a protein sequence.
The multiple theory is used in such a way which is analyse the model or a method which show
the biological method. There are number of most scientific paper and survey show the time and
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indeed. Despite of a large number of in silico analyse depend on the MSA method. These
include domain analysis which show the factor of domain analysis, phylogenetic reconstruction
which is depend on the motif finding and a whole range of other applications, extensively used to
provide the range of applications and this is well described.
Multiple sequence analysis which is used to show the important modelling tool which is
associated with the development that is required for the addressing a complex situation which
help to provide the collaboration of computational and biological issue. In this, the computation
of an accurate multiple sequence analysis shows the long-term factor which is known by NP
complete problem, situation that explain why this alteration method have been developed these
past three decades. The multiple sequence analysis shows the method and their application which
is show the several review.
In addition to this, the MSA show the various number of results on the basis of 10 amino
acids as per the acid sequence which is associated with the 10 amino acid. The M protein which
is comes under the form the various coronavirus (4 SARS-associated and 6 other known). The
model is basically used in the profile of HMM (hidden Markov model). This model shows the
various training was implemented through the SAHMM which is called as the self-adapting
hidden Markov model. This software is developing by number of authors for their safety and to
analyse the sequentially pattern of protein.
Some of the researching unit evaluate the protein sequence analysis of coronavirus such
as they used to provide the following sequence for coronavirus which is included such as:
Amino acid composition analysis: In this, the use of single sequence, multi-sequence analysis
and other techniques which help to provide to analyse the component of amino acid composition
analysis.
Protein motif prediction: In this, the motif amino acid which comes the sequence pattern that
help to stabilise the signature of the protein family and this show the vital important biological
significance. This can be predicted which show the presence of motif protein that analyse the
protein function.
Signal peptide prediction: This all well analyse the signal peptide which is used to follow the
section of the N terminus of most of the formulation of synthesize protein and this help to
contribute the protein which show the presence of transport and hidden Markov model which
help to provide the channel of variety for the cell sequence.
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Transmembrane prediction: For the protein which is show the factor of transmembrane which
must be analyse and include the factor and prediction level of extracellular and intracellular
region which used to show the number of chain function that create the protein and crosses the
membrane.
Binding sites prediction of the ligands: This help to provide the template based, geometry based
which is energy based and combination-based method which help to predict the protein ligand
binding as according to site distinguishing factor as a term of properties.
Some of the application which is used to follow in the protein sequence analysis in the
coronavirus research. Some of them are:
 Compare the protein and their sequence which is used to show the similar and infer
whether they have multiple protein are homologous in nature.
 In this context, they are used to show the difference and various mutations between the
multiple and show the level of protein in this aspect which is used to define the higher
protein sequence.
 As per this, they play role in the development of various molecular structure from the
sequence.
 They help to determine the various number of intrinsic characteristics of the sequence as
per by using the PTM site and various active receptor site as per regulatory body.
 They used to show the relevancy of protein evaluation and diversity.
The effect and impact of the variance mutation on vaccine efficacy.
In addition to this, the most viral mutation which show no impact on the virus ability to
cause the infection and the overall disease. This all are depending on the changes which show the
located in the virus genetic material which have ability to may affect the properties of the virus.
In this, there are number of transmission state which is used to show the example which help to
spread more and less easily. This may also assist them in the severity and provide additional and
less severe disease. Moreover, the coronavirus vaccine which is usually produced and develop in
such a way which develop the expected time for some protection against new variants. As per
this, there are number of factors which show the effectiveness of vaccine in order to broad
spectrum and this show the huge immune response that associated with the antibodies and cells.
Therefore, changes or any kind of mutation can cause various problem which is related with the
virus. In this, events if any kind of medicine or vaccine are used to show the impact which help
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to prove the vaccine against the effective one or more number of variants which is visible and
show the impact of composition of the vaccine in order to provide the information against the
variability and variants. In order to this, the world health organisation show the tracking mutation
and variants which show the feasibility and since as per this they start to show the factor which
show visibility.
In order to this, the data which is stable and show the continuation which has been
collected and analysed on the faith of new variants which is related with the covid. In aspect to
this, the World health organisation have number of researcher and they collected the data. These
variants show the effect of virus and behaviour which help to include the impact of effectiveness
of vaccine. In this, all factor is more stable and show the information which is used to provide
the impact of covid-19 variants. This region is so particulate and this help to provide the
evidence that is preliminary in nature and provide a core of development in quickly. In order to
this, the world health organisation show the tracking mutation and variants which is occur as per
during the initial state of the covid outbreak. The SARS-CoV-2 have huge network and they
must include the dedicated virus evolution working and they have their particular group and
region of changes which is possibly impacted the new developing stage of vaccine. In this order,
the World health organisation is also used to established the condition of SARS-CoV-2 which is
helping in order to show the factor and other factor which may create the monitoring and
evaluation which have ability to show the framework to know and identify monitoring and assess
variants in the option of concern. This also help to improve the component that used to show the
surveillance research on the factor of variants. This all framework is used to serve as a guide and
this show the capitalisation of the manufacturing and countries on the behalf of particular change
which may needed for the covid vaccine.
With relation to this, the future variant may also create number of factors which is
associated with the covid. This all factor are well stated and used to provide the current measure
which used to minimise the transmission that include the frequent hand washing, wearing a mask
, also the norms and guidelines are circulated in this and show the additional factor such as
maintain of the social distancing, physical distancing, good ventilation and avoiding the crowd
factor which show the necessary places or closed setting which have ability to make the setting
to continue to work against new variants by minimising the amount of the viral transmission
which reduce the opportunities for the making of new virus and to form new mutate.
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Impact of the mutation on pathogen-city, epidemiology and diagnosis.
Mutation is defined as the natural product which is defined by the product and viral
replication. Whereas, the RNA virus is used to show the higher mutational rate in term of DNA
virus. In addition to this, the coronavirus shows the fewer changes in their DNA and form the
consideration of the mutation. As per this, the mutation in show the RNA virus because they
code an enzyme that corrects some of the error made during provide the replication. In most of
the cases, they are trying to newly arising mutation is determined by natural selection. They are
show the competitive advantage with respect to viral replication, transmission which is help to
provide from the immunity will enhance in frequency. Moreover, mutation can also help to
enhance and decrease in frequency due to the chance of events. As per the example, there are
founder effect which is when a limited number of individual virus establish a new population
during transmission. The mutation present in the genomes of these viral ancestor which is
dominate the population regardless of their effect on viral fitness. This same interplay of the
natural selection and chances events shape virus evolution within host. There are number of
community and across countries such as UK, Brazil and South Africa.
Evaluation of the new SARS which show the variant probability. This may create the
factor and in term of mutation, there are number of variants which show the strain and describe
the other epidemiology of the SARS which show the measurement of the distinction. As per this,
mutation is defined as the change in the DNA of D614G is an aspartic acid to glycine and this
also help to hold the condition of 614 of the spike glycoproteins. In this, the genome which show
the sequence are often called as the variant. In addition to this, they are used to define as the
factor which show the precise because this make affects the mutation any way. As per this, the
strictly speaking that the three are number of strains which is usually help in the factor of
phenotype which show the difference in antigenicity which show the faced and this can be
transmissibility or by the virulence.
The D614 which is a mutation in the spike glycoprotein of the virus SARS was noticed in
the march of the 2020. They create dominance in the world after a few times. This mutation is
initially started and show the factor of independently which was suggested and show the multiple
sweeps along the geographic region. Moreover, the proper use of the D614G mutation which is
help to identify dispersal of the spike protein and their affectivity in the individual.
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Factors affecting the efficacy of vaccine
According to Petra Zimmermann, (2021), there are many of the factors which are there in
the medical science that can have different effect on the efficacy of vaccine that can be there due
to effect and the response of getting change in response of vaccine on human being. For better
performance of COVID vaccine it is needed to have focus on factors which have the high chance
to affect the efficacy of vaccine. There are different factors which should be focus on to provide
better effect of vaccine to all over population in same and efficient manner. In terms to regulate
vaccine to different corner of world there are different factors that can have different effect on
efficacy of vaccine. Some of the factors are discussed further (Chan and et, al., 2020).
Long term safety profile of vaccine- This one is highly effective factor which can have
high impact on efficacy of vaccine. World have immediate need of vaccine and to provide and to
save human being from high loss of people, formulation and vaccine formation is quite fast
rather than standard time. This could impact the efficacy which is due to there are late response
on medical term. Sometimes, to show some side effect or adverse effect there is chances of
getting different health related issues in future. This can lead to different problem in future with
can have the threat of life and living hood. There is short term safety approved vaccine where
there is chance of induction of anaphylactic reactions which can be in some of the vaccine
recipients hasn't helped optics with vaccine hesitancy. There are rare chances of this situation
which are generally can be associated with severe allergies. There in report there about 23 frail
elderly individuals who are there in Norway died after receiving vaccine that was from Pfizer.
There is no any proof and reason for these deaths but after knowing some specific result there is
no change in the regulation of vaccine. In response to find the cause there is pressure on
physician that to find out the ages which should need early vaccination and which age group
should have high risk of negative response after vaccination. In future there is high chance of
severe side-effects which should be there in relation to withdrawal of approval of vaccine. So,
time is the factor which should be there can have the impact on the efficacy of vaccine.
Duration of immunity- This is another factor which have the effect on the efficacy of
vaccine. In this, duration represents here about the how long time after vaccination any person is
protected. In previous vaccine there was the duration which was associated with few years. In
this, there were effect on person about one year and in this duration their person body get
adopted and achieve the herd immunity but in case of this vaccine there is only month as the
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duration of vaccine and due to this when human body get declined the immunity before herd
immunity then there could be chance of getting susceptible to infection again and could be the
chance of roll-out failure. This could be the factor which is able to affect the efficacy of vaccine.
Variants risk that can evade induced immunity of vaccine- This is the one in which
there is high chance of getting induced of different variants of SARS which are identified in
recent time. In this, corona virus is able to copy genetic material of SARS and able to induces
random mutation which cause the high chance of survival of coronavirus in vaccinated people
who have induced of vaccine. There could be chance of disaster of immunization strategy. There
is very less chance to quantified accurately about eh risk of mutations which evade vaccine
immunity. Current vaccine which confers narrowly focused immunity which is able to target
single viral spike protein. When variant emerges and can alter spike protein is able to bypass
vaccine-induced immunity there is chance of failure of vaccine roll-out. This can be factor which
can affect the efficacy of vaccine (Mycroft-West and et, al., 2020).
Untested vaccine regimens- This is the one in which there is need to vaccinate two
doses of vaccine in some specific interval of one dose and any alter in the dose interval, can lead
to not getting effective action. There is no any evidence regarding performance of vaccine which
is due to alter in the interval differences which is there is due to logistical challenges which are
there due to effect of maximizing and quick vaccination within population. Single dose regimens
and combining vaccines that is from different manufacturers are able to alter the dose interval.
This can be the factor for affecting efficacy of vaccine which is there can be due to alter in
vaccination of second dose.
Herd immunity- This is the one which is known to get adopted with virus and don't have
any negative effect of virus on human health. This is the one which is there able to get change in
the efficacy which could have the chance that when there is no better and effective impact of
vaccine on human being which is due to continue mutation of virus. There is high chance of
getting difficulty in adaptability which are there provide strong immune system regarding
coronavirus where body got adopted against it and there is no any physiological or pathological
change in human body. Due to herd immunity, there is chance that vaccination could have
different impact on body which should be evaluated. Like this, herd immunity has the chances to
affect the efficacy of vaccine.
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Insertion of any different drug- This is the one which could have the chances of create
the impact on efficacy of vaccine which is there due to using of different drug which could have
the chances to alter the mechanism or there are chances of getting different impact on the
pharmacological impact on body or due to change in physiological change or any chemical
change in body due to vaccination. This can create different health related issues which can have
chances to get impacted by different medicine which can lead to change in the efficacy of
vaccine in human body or in some person (Jaimes and et, al., 2019).
These are some of the factors which are there able to alter or affect the efficacy of
vaccine in human body either in long term or just after vaccination.
Structural difference between variant protein (S, E, M & N)
There are some of the differences in the structure of various protein where S represents
Spike, E represents Envelop, M represents Membrane and N represents Nucleocapsid.
Structure of spike- S protein consist of transmembrane domain anchored that is in viral
membrane, extracellular N-terminus along with short intracellular segment of C-terminal. In this,
when virus interacts with host cell, there is occurrence of S-protein extensive structural in which
allows virus to fuse with host cell membrane. In this, there is coating of polysaccharides which
are on spikes for camouflage them, that is for surveillance of host immune system at entry time.
Length of SARS-CoV-2 S is 1273 aa which is consist of single peptide at N-terminal. S1 and S2
are the subunit which are responsible for membrane fusion along with receptor binding. Trimers
of S protein visually forms characteristic bulbous, which is a crown like halo covering the viral
particles. Just like S protein monomers there is S1 and S2 subunits which form stalk region and
bulbous head. Structure is determined by cryo-electron microscopy which is at atomic level.
13

Structure of E protein
There is need to uncover the structure of various novel virus proteins. As currently there
is no structure of SARS-CoV-2 E protein and should be there by comparing with SARS-CoV
envelop protein (Chowdhury and et, al., 2020). There are differ topology which are there based
on three domains that is short hydrophilic N-terminal, long hydrophilic C-terminal and long
hydrophobic transmembrane domains. There are two different forms of E protein, there is
monomeric structure, oligomerizes in order to form pentameric viroporin that is there in host
cell's Golgi membrane.
14

Structure of M protein
M proteins is composed of three putative TM domains which is one third of entire
protein. It located between Codons 19-98 in ORF. There is first TM domain which is composed
of 19 a.a. Residues. This is non-polar and neutral amino acids which accounts for substantial
fraction of domain. Second domain is between 50-72 codons which is 81% neutral residues and
non-polar in nature. There is amino-terminal exterior which are composed of 18 codons. There is
glycosylation site that is found at Codon 4 and carboxylic terminal region composed of 123
residues.
Structure of N protein
Nucleoside protein package viral RNA that is there to form helical capsid which is
essential for viability. N protein contain two different structural domains which are flanked by
disordered segments. They act as putative RNA binding domain which is at N terminal domain.
At C-terminal domain, there is fragment containing residue which was interactions of multiple
hydroponic (Drew and et, al., 2020).
15

RESEARCH METHODOLOGY
Research methodology is referring the process which is help researcher to collect and
analyse the data. As per this, the researcher has their significant ways to determine the data and
information which is based on the topic. In context with this, a researcher has many of view
which used to show the topic and help to identify the various factor which may be create with the
topic. Moreover, this help to identify the elaboration of the topic and this help to state which is
help to conduct the study. In this, the main objective of this section is top conduct positive
research methodology. For conducting any type of research methodology this is well analyse that
the proper source and facto are used in this, the methodology used to provide an identification of
various factor which is associated with the topic and process of research. The concept behind the
conducting of research in this topic is appropriate and help to identify the number of factor.
Moreover, the research and their question which help to show the opinion and examination are
well. They are used to show the number of people and this all provide the rationale and support.
They used to provide the proper evaluation and this all approach are helpful for the conducting of
research. Without the proper method the research drive with the biased decision. This all are
used to show the well-defined and proper structure in order to show the framework which have
accessibility in designing of the positive and effective research which is associated with the
given topic (ur Rehman and et, al., 2020).
Research philosophy: There are number which help to show the usually concern with the
two type of the philosophy which is defined with the technique of interpretivism and positivism.
According to the topic, this all are used to show need proper in the term of investigation which is
for the particular matter of research. In context with this, the interpretivism is refers as the
evaluating of data or to concern effectively and this help in the conducting. Moreover, there are
various factor which is accessible in this which help positivism philosophy which is not related
for the proper systematic manner. This all are conduct in appropriate way which provide the
relevant sources.
Research choice: In context with this, there are two type of research which is qualitative
and quantitative. In order to this, they are used to show the various approach which is associated
which help show the number of patterns which is related with the quality of approach. In this
aspect, the qualitative research provides the source of information. In this, there are some of the
qualitative and quantitative which is order which help create the valuable and more appropriate
16

for because which is used to show the provide the investigation that help to provide the
investigation that help to make the response more proper and confined.
Time duration: The time duration is state that the research period. In this, it helps to provide
the information which help to support and analyse the starting point and ending time which is
associated with the completion for the various aspect of research and them activates that is taking
under the conducting of research. In this, the proper model and theories are used in this which
help to provide the information which is relevant to the topic and provide major evidence in the
research. In this, they are used to show the significant role and this all are used to provide the
basic knowledge to upgraded skill while performing the research (ZangirolamiRaimundo and et,
al., 2018).
Research design: This section and is defined the way of designing the research. This all are
used to provide the kind of blueprint which is usually help to create the structure which is
accessible for the design of study which is associated with the organising and conducting pattern
of project. As per this, they are used to show the factor which is serve as the master and
appropriate plan and standard operating procedure. This all are well established and show the
fact which is help to create the issue which is related with the proper ways and this evaluate the
information that is overtaken by the process of decision making and to analyse the core concept.
Source of data: In order to this, the research is based on the various section of source factor.
As per this, for the collection and for gathering of data the secondary research is taken place and
with this the significant value and finding is observed. In context, the proper primary research
are studies to identified the factor and co factor which help to access the number of secondary
data. Moreover, they are used to take to various applied question for the analysis of topic related
information. In this, they are accumulated the data and this is collected by the proper conduction
of research process by using the method of secondary research. For this, the books and peer
journal review are overview and show the impact of published and unpublished article are
reviewed (Bisdas and et, al., 2019).
Data collection: In context with this, there are number of factors which is associated with
the data collection and this help to show the impact which is accumulated by the primary source
of factor such as by using the term of direct interview and or by using the questionnaire. The
question is help to find the evidence which is valid and related to topic that develop the proof.
Hence, this approach is reliable and useful for the gathering of relevant data.
17

Data sampling: A sample which is used to show the process and operation of data collection
and used to create the base of proof and evidence. In context with this, the procedure which is
followed by the researcher for the collection of data include the random, straight, judgemental
random and applied as per by using the right sample size which is inclusive in nature. Thus, this
all aspect which is mentioned above is provide the area for the research and provide the
information about the topic and research (Flick, U., 2020).
Data presentation: There are number of factors which is used to provide the presenting
which is have some of the selected fraction. Thus, this all fraction is used to distinguish the
number of data and information which is selected and collected are in appropriate way. This all
help to show the pie chart and various table in order to create the path and allow to create the line
graph which help to define the proper factor which is associated with this which is related to the
topic.
Research ethics: While conducting any research, the primary research is used to take and
ensure the outcome of the study which is considered as the factor which is relevant in nature.
This is used to provide the accurate information which is about to take the objective and research
which help to show the contribution that is show some the factor which is essential for the
appropriate. This all used to create some of the factor which may be relevant and provide the
ethical consideration which is used in the research for the positive attitude for the research. This
help to maintain the prolong membership with the attribute while conducting of research.
Research limitation: As per this, there are number of factors which is associated with the
limitation or face the issue that is associated with limitation. There are number of physical and
primary search that is being under the survey which is used to show some of the objective which
have used in implementation of the objective which is performed under this. The proper data and
knowledge are being used in such a way which help to ensure the limitation and allow some of
limitation is in useful way (Delavega and et, al., 2017).
Research reliability and validity: Reliability and validity of the research topic which is
mainly depend on the equipment and techniques that are used to analyse the proper
questionnaire. There are some of the essential approaches is help in the context with the
researcher which is evaluate the information and provide their research. As per this, it states
about the various factor which is important to show the research compatibility and adaptability
18

which is used to show the some of the impact which is necessary and provide the reliability and
validity to the research.
Summary of the chapter: In context with this, this chapter state about the covid and their
variant which is collaborated with the number of divisional fractions which is associated with the
spike protein. There are number of proteins which show the difference in their protein and some
of the factor which decrease the efficacy of vaccine. With this, the structure of the spike protein,
membrane, envelope and nucleocapsid which is associated with covid factor. This all are sated
with the coronavirus. As per this, they are shown the sum of multiple sequence and their
analysis. Whereas, these are studies are well associated with the other in which they are being
created and analyse that they are study about the impact of the mutation which affect the vaccine
efficiency (Vasilevskaya and et, al., 2017).
RESULTS
Introduction to the chapter: In this, the covid in spreading into worldwide and create number
of issues which is related with health and create the complication which may cause fatal stage.
As per this, they used to create number of issues which is faced by number of populations. In the
recent time, the covid is possibly in their peak point and used to formulate various factor which
is may be cause life threatening issue. As per this, the anatomical development which is related
with the covid are like this topic or research state about the phylogenetic analysis of the different
type of protein which is observed under the covid. They play important role as per identified the
studies such a they have large number of clinical trials which is being conducted on the situation
of covid. Moreover, SARS-CoV-2 which is show the single stranded RNA-enveloped virus. In
this, the RNA-based metagenomics next-generation sequencing which is characterise by the
genome form that is shown entirely genome (Sah and et. al., 2020). The S, E, M and N gene
encode which help to show the structural, whereas, they show the non-structural protein which is
associated with the 3 chymotrypsin such as protease, papain like protease and RNA dependent
which is associated with the RNA dependent RNA polymerase which is encoded by the ORF
region. A large number of glycosylated S protein which help to cover the surface of the SARS-
CoV-2 which help to bind host cell receptor which show the angiotensin converting enzyme.
Mediating viral cell entry which is S protein bind with the receptor and they are show the
protease located on the host cell membrane which used to promote the virus entry into the cell
that help to activate.
19

As per this, they have proper multiple sequence analysis which have proper analysis of
protein in which they have further and used to analyse the co factor and dimensional unit which
is used to provide the fractional data that is involved in the flow of portion and they are provide
and essential look of the multiple sequence. This sequence is undertaking and analyse that the
concept and the sequence is based amino acid. This all sectioned and this all based with the
proper allocation of peptide band. In this other are associated with this which is above discussed
in the brief. The other part of this well discussed ass shows the facto which is help to show the
effective (Zhang, H. and Zhang, C., 2021).
Result of objective: As per this, they are used to take the concept of phylogenetic analysis in
order to this they help number of issues. There are number of proteins which is associated with
the analysis of various protein structure. In this context, the protein which is associated with this
is spike protein, membrane protein, envelope and nucleocapsid which is associated with the
structural protein which is shown in the capacity of covid. This all protein helps to covid to grow
faster and with proper speed they enter in the body of host and replicate their origin inside the
host and cause various of complication. They indirectly provide nutrition to the virus and this
help to enhance the flow of growth and they are easily transmitted from the one place to another.
In this, these proteins play the vital role in the development of virus and they provide extra
support while they are replicating itself. The phylogenetic analysis provides number of
additional information which is incorporated with this a provide number of additional supports to
the covid genome to grow further and help in the mode of replication by providing them proper
nutrient (Hussain, S., 2017).
A virus has a multiple number of sequences which is associated with the chain which
may be kind of polypeptide chain. As per this, the multiple sequence usually has ability to
refurbish the core of development and provide the quantum base factor which is may be
associated with sequence chain. As per this, they have number of complications which is arise
due to the non-uniform factor which may be arise in the sequence and this inhibit the overall
function and physiology. This all help to provide the core matter which help to show the other
essential core which is usually provide an additional major and factor which is admirable in term
of multiple sequence (Neupane and et. al., 2020).
The variant which is arises due the mutation which is cause under the various
consequence. As per this, the effect and the impact which is formulated under the variance
20

mutation which is cause for the vaccine efficacy. In context with this, they are used to show the
factor which is accessed by the vaccine, there are various complication which is may arises due
to the protein and other related deviation which is caused by the matter of vaccine. Vaccine is
type of dose which is used to provide the antibody which help to fight against the infectious
matter which is already present under the body or host. Moreover, mutation is defined as the
growth of abnormal cell in appropriate manner and create the deviation. As per this, mutation is
defined as the core concept which help to provide a new idea and new core of factor. In context
with the mutation, the covid virus cause number of mutations which is used to show replication
and change their pattern. This pattern creates the number of consequence and decrease the
impact of vaccine and cause various issue (Saha and et, al., 2020).
Mutation cell which diverts the function and factor which is cause inside the host cell. As
per this, they are change in their pathogenesis and epidemiology and they have differed in their
pattern. This mutation in the cell of covid virus can cause number of complication and make
them resist for the vaccination, as per they develop extra layer of cell wall and cause various
issue which is associated with this issue. Usually, the covid have number of variants from the
past, there origin is basically a mutation and after it this recent covid which is appear in year
2019 is more mutant and combine itself as a deadly virus.
As per this, every year of time, this is determined that the virus change their pattern and
cause various complication which is associated with this, the mutation can birth another type of
gene and they lead to change their origin and cause number of issues which is related with the
host body. Moreover, some the mutation can cause and transform into the deadly virus
(Chatterjee, S., 2020).
Summary of the chapter: In this, there are number of studies which is associated with this
help to analyse the core concept of covid and their related with the corona virus. This all helpful
for the phylogenetic analysis which is associated with the four type of structural protein such as
spike, membrane, envelope and Nucleocapsid. In this, the study is also conducted in the
objective of multiple sequence analysis which is related to the protein and help to give the
information about the chain and peptide which is made up of amino acid. As per this it helps to
analyse the impact and effect of the variance which is based on the mutation on vaccine efficacy.
As per this, they are stated and raise a finding about the pathogenicity, epidemiology and
diagnosis of the virus which may change their structure. This mutation can cause number of
21

diversions in the efficacy of vaccine which may arise due to the factor of resistivity (Ahmad, S.I.,
2020).
22

FINDING, DISCUSSION AND CONCLUSION
Introduction: From the above study it has been concluded that COVID-19 is the pandemic
disease which is cause by the coronavirus, from the beginning of its first case ill now health care
organisation and researchers are working for the develop its medical way of control and
treatment. But due to its uniqueness and mutation researchers are facing the huge problem in
successful vaccine development. One of the leading cases of coronavirus mutant is SARS-CoV-
2, this is the type of airborne disease known as severe acute respiratory syndrome, that is caused
by the associated factors COVID. This is the communicable disease and it can harm the numbers
of people due to the social gathering and other mode of interaction. The virus that caused the
COVID-19 is the variant of the SARS family, there is the major reason of vaccine
ineffectiveness is that virus used to grow through the spike protein (Majumdar and et, al., 2020).
Findings and discussion: This research is done in context to that information and virus
identification gap specific research is done, within the aims and objective of determining the
impact of SARS CoV-2 variants’ mutation on pathogenicity, diagnosis and vaccine. For this
research quantitative method is used. There is the major regional research is considered such as
the relevant information related to the species and their protein. One of the objective of this
report was Analysis and evaluation of the information related to the Phylogenetic of virus
protein, then in other hand analysis multiple sequence of the proteins, effect and impact of
variance mutation on vaccine efficacy, impact of mutation on pathogenicity, epidemiology, and
diagnosis, mutations affect the efficacy of the vaccine, structural difference between the variants’
proteins, these all were the objectives of research in context to the achievement of selective
research outcome which can be further helpful in the vaccine development. From the
accomplishment of all these objectives it has been fund that, phylogeneticity is defined as the
development and diversification of a species and all this aspect is based on the protein which
have significant structure and they have proper trait, which helps in the grouping of species
according to their protein content. SARS-CoV-2 which is associated with the Beta coronavirus
belonging from the coronaviridae family (Bonomi and et. al., 2020). Coronavirus is enveloped in
the positive sense which is associated with RNA virus with the large factor and create the non-
segmented genome. There are the five major open reading frame such as ORF1a, ORF1ab
analysed and these all four structural proteins which is associated with the plus a number of
accessory gene. The coronavirus which is associated with S protein which is trimeric
23

glycoprotein which that is belong to the class one fusion of test, S1 receptor binding domain
(Oniani and et, al., 2020). Bas TMPRSS2 in the form of rupture site such as S1/S2 which show
the data of poly basic such as motif at the S1 and S2 boundary. E protein is less abundant
protein show the essential assembly and as per this there are various interaction with the M
protein, this all protein is associated with the critical aspect of the viral life cycle and this lacking
the e protein. The mutation properties of the virus are the biggest issues of the COVID-19
vaccine development and some of them make promising vaccine for the candidate. Multiple
sequence analysis of the protein is done; this is the type of protein modelling tool which is
important in the process of biological solution development. HMM (hidden Markov model) is
used for the multiple sequence analysis the Protein motif prediction, Signal peptide prediction,
Transmembrane prediction, Binding sites prediction of the ligands are used in this MSA process.
Then in net step impact of the variance mutation on vaccine efficacy is analysed according to
which the SARS-CoV-2 have huge network and they must include the dedicated virus evolution
working and they have their particular group and region of changes which is possibly impacted
the new developing stage of vaccine. This information is can be effective in health care guideline
development which can prevent the case and virus mutation. Then another objective is
accomplishing in context to the mutation on pathogen-city, epidemiology and diagnosis.
According to this objective analysis The D614 which is a mutation in the spike glycoprotein of
the virus SARS was noticed in the march of the 2020 (KleinRichers and et, al., 2020).
Conclusions: From this critical research it has been fund that COVID-19 vaccine is not
working due to the highly mutant nature of the coronavirus protein which is belonging to the
SARS virus group. Mutation changes the replication and function of the virus due to which virus
get fail in the virus control, such as the five major open reading frame such as ORF1a, ORF1ab
structural protein of the virus which contribute in the mutation. From some study and research
information it has been fund that D614 is a mutation in the spike glycoprotein of the virus SARS.
Recommendations and suggestion: This mutation property is can be more effectively
analyse and controlled by the effective practical primary research, under which researchers can
use D614G mutation which is help to identify dispersal of the spike protein and their affectivity
in the individual. Effective norms and guidelines are circulated in this and show the additional
factor such as maintain of the social distancing, which can be helpful in the disease control and
give time for the effective research of the level of virus mutation (Matyášek and et. al., 2020).
24

Summary of the chapter: This report is state about the various aspect of coronavirus such as
it states about the number of virus protein structure with in the approach of phylogenetic
structure of the different type of structural protein, spike membrane and sensitive protein,
nucleocapsid. This report is about the virus protein sequencing which can help in the analysis of
virus mutation and effective successful vaccine development (Korber and et, al., 2020).
25

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