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COVID-19 VIRUS UNCOATING AND

TREATMENT

Shivani Pande Amit Bhoyar

shivanipande1999@gmail.com ahbhoyar@gmail.com

L.A.D college, Nagpur NSA India, Nagpur

ABSTRACT treatment. Though the vaccines are not yet


available,but can be made using genetic material of
Coronavirus disease (COVID-19) is an infectious virus as like vaccine-derived poliovirus (VDPV), in
disease caused by a newly discovered coronavirus. oral polio vaccine(OPV) contains an attenuated
Most people infected with the COVID-19 virus will (weakened) vaccine-virus,activating an immune
experience mild to moderate respiratory illness and response in body,so by using the concept we can
recover without requiring special treatment. Older make an antidote of COVID-19 .An another way to
people, and those with underlying medical problems stop COVID-19 in humans is increase the humoral
like cardiovascular disease, diabetes, chronic immunity of humans by Supplements or any
respiratory disease, and cancer are more likely to medicine,which resists against the virus. In short,
develop serious illness. Coronavirus are the second reducing the activity of virus increasing the
leading cause of the common cold (after strength of immunity. Or by reverse transcripting
rhinoviruses) and until recent decades, rarely the genetic material of the virus as it contains single
caused any disease more serious than a common stranded RNA as genetic material,by reverse
cold in humans.The first coronavirus was isolated transcripting RNA and modifying it into double
in 1937. Some cause illness in people and others stranded DNA,which will disable the activity of the
circulate among other animals, including camels, virus .When this artificially modified DNA will
cats and bats. Since its discovery, related comes in contact with the cells ,the golgi bodies of
coronaviruses have been found to infect cattle, pigs, cell starts to replicate this DNA,so this can reduce
horses, turkeys, cats, dogs, rats, and mice. The first or stop the activity of SARS-CoV-2.
human coronavirus was cultured in the 1960s from
nasal cavities of people with the common cold. The Keywords: CoronaVirus, Covid_19,SARS-CoV-2.
new SARS-CoV-2 virus which is responsible for
recent outbreak in Wuhan,China is also from
Coronavirus family.As per most of reports uptil
1. INTRODUCTION
now,this virus is transmitted to humans through
Bats from Wuhan's raw meat market.World health SARS-CoV-2 is a new virus which belongs to the
organization [WHO] has declared this,as pandemic coronavirus family. coronaviruses were only thought
disease on 11 March 2020.Today many countries all to cause mild, self-limiting respiratory infections in
over the world are facing this pandemic crisis and humans. Two of these human coronaviruses are α-
researchers all across the world are trying to coronaviruses (HCoV-229E and HCoV-NL63)
vaccine or antidote of it.Here we have given the while the other two are β-coronaviruses (HCoV-
details of SARS-CoV-2 and idea of vaccination and OC43 and HCoV-HKU1). HCoV-229E and HCoV-
OC43 were isolated nearly 50 years ago while of age. The outbreak began in a hotel in Hong Kong
HCoV-NL63 and HCoV-HKU1 were only recently and ultimately spread to more than two dozen
identified following the SARS-CoV outbreak . These countries. During the epidemic, closely related
viruses are endemic in the human populations, viruses were isolated from several exotic animals
causing 15–30% of respiratory tract infections each including Himalayan palm civets and raccoon dogs .
year. They cause more severe disease in neonates, the However, it is widely accepted that SARS-CoV
elderly, and in individuals with a greater incidence of originated in bats as a large number of Chinese
lower respiratory tract infection in these populations. horseshoe bats contain sequences of SARS-related
HCoV-NL63 is also associated with acute CoVs and contain serologic evidence for a prior
laryngotracheitis (croup) . One interesting aspect of infection with a related CoV . In fact, two novel bat
these viruses is their differences in tolerance to SARS-related CoVs were recently identified that are
genetic variability. HCoV-229E isolates from around more similar to SARS-CoV than any other virus
the world have only minimal sequence divergence identified to date . They were also found to use the
while HCoV-OC43 isolates from the same location same receptor as the human virus, angiotensin
but isolated in different years show significant converting enzyme 2 (ACE2), providing further
genetic variability . This likely explains the inability evidence that SARS-CoV originated in bats.
of HCoV-229E to cross the species barrier to infect Although some human individuals within wet animal
mice while HCoV-OC43 and the closely related markets had serologic evidence of SARS-CoV
bovine coronavirus, BCoV, are capable of infecting infection prior to the outbreak, these individuals had
mice and several ruminant species. Based on the no apparent symptoms . Thus, it is likely that a
ability of MHV to cause demyelinating disease, it has closely related virus circulated in the wet animal
been suggested that human CoVs may be involved in markets for several years before a series of factors
the development of multiple sclerosis (MS). facilitated its spread into the larger population.
However, no evidence to date suggests that human
CoVs play a significant role in MS. SARS-CoV primarily infects epithelial cells within
the lung. The virus is capable of entering
macrophages and dendritic cells but only leads to an
abortive infection . Despite this, infection of these
cell types may be important in inducing pro-
inflammatory cytokines that may contribute to
disease . In fact, many cytokines and chemokines are
produced by these cell types and are elevated in the
serum of SARS-CoV infected patients . The exact
mechanism of lung injury and cause of severe disease
in humans remains undetermined. Furthermore,
Fig 1: 3D modelling of Coronavirus animals infected with rodent-adapted SARS-CoV
strains show similar clinical features to the human
1.1. SARS-CoV disease, including an age-dependent increase in
disease severity . These animals also show increased
SARS-CoV, a group 2b β-coronavirus, was identified levels of proinflammatory cytokines and reduced T-
as the causative agent of the Severe Acute cell responses, suggesting a possible
Respiratory Syndrome (SARS) outbreak that immunopathological mechanism of disease .
occurred in 2002–2003 in the Guangdong Province of
China. It is the most severe disease caused by any 1.2. SARS-CoV-2
coronavirus. During the 2002–2003 outbreak
approximately 8098 cases occurred with 774 deaths, Severe acute respiratory syndrome coronavirus 2
resulting in a mortality rate of 9%. This rate was (SARS-CoV-2),previously known by the provisional
much higher in elderly individuals, with mortality name 2019 novel coronavirus (2019-nCoV), is a
rates approaching 50% in individuals over 60 years positive-sense single-stranded RNA virus. It is
contagious in humans and is the cause of the ongoing
pandemic of coronavirus disease 2019 (COVID-19)
that has been designated a Public Health Emergency
of International Concern by the World Health
Organization [WHO]. SARS-CoV-2 has close
genetic similarity to bat coronaviruses, from which it
likely originated. An intermediate animal reservoir
such as a pangolin is also thought to be involved in
its introduction to humans. From a taxonomic
perspective, SARS-CoV-2 is classified as a strain of
the species severe acute respiratory syndrome-related
coronavirus (SARSr-CoV).
disease, lung disease and diabetes, for example —
The strain was first discovered in Wuhan, China, so it seem to be at higher risk of developing serious
has sometimes been referred to as the "Wuhan virus" COVID-19 illness.From a study ,it seems that people
or "Wuhan coronavirus". Because the World Health with 45+ age group are at high risk .
Organization discourages the use of names based
upon locations and to avoid confusion with the
disease SARS, it sometimes refers to the virus as "the
virus responsible for COVID-19" or "the COVID-19
virus" in public health communications.

The SARS-CoV-2 virus is a betacoronavirus, like


MERS-CoV and SARS-CoV. All three of these
viruses have their origins in bats.Early on, many of
the patients at the epicenter of the outbreak in
Wuhan, Hubei Province, China had some link to a
large seafood and live animal market, suggesting Graphical representation of risk factor in age groups.
animal-to-person spread. Later, a growing number of
patients reportedly did not have exposure to animal SARS-CoV-2 is an airborne disease and spreading
markets, indicating person-to-person spread. Person- rapidly among all the countries of the world like
to-person spread was subsequently reported outside forest fire,daily new cases are reported.Apart from
Hubei and in countries outside China, including in this a relief news is that,although cure or treatment is
the United States. Some international destinations not yet discovered,some patients are recovering
now have ongoing community spread with the virus succesfully.
that causes COVID-19, as do some parts of the
United States. Community spread means some people
have been infected and it is not known how or where
they became exposed.

The complete clinical picture with regard to COVID-


19 is not fully known. Reported illnesses have ranged
from very mild (including some with no reported
symptoms) to severe, including illness resulting in
death. While information so far suggests that most
COVID-19 illness is mild, a report external icon out
of China suggests serious illness occurs in 16% of
No.of increasing cases and recovery and death cases
cases. Older people and people of all ages with
severe chronic medical conditions — like heart
electron microscopy, is the protein responsible
for allowing the virus to attach to the membrane
of a host cell.

Fig 2 CoronaVirus Structure with RNA and protein


Spikes

Protein modeling experiments on the spike protein of


the virus soon suggested that SARS-CoV-2 has
A report and graph by the World Health Organization [WHO],upto sufficient affinity to the angiotensin converting
25th March.
enzyme 2 (ACE2) receptors of human cells to use
1.3. INFECTION THROUGH SARS- them as a mechanism of cell entry. By 22 January
CoV-2. 2020, a group in China working with the full virus
genome and a group in the United States using
The exact origin of infection is not known but reverse genetics methods independently and
according to previous reports,the infection was first experimentally demonstrated that ACE2 could act as
transmitted from Bats to human and then human to the receptor for SARS-CoV-2. Studies have shown
human. And Human-to-human transmission of that SARS-CoV-2 has a higher affinity to human
SARS-CoV-2 has been confirmed during the 2019– ACE2 than the original SARS virus strain. SARS-
20 coronavirus pandemic. Transmission occurs CoV-2 may also use basigin to gain cell entry.
primarily via respiratory droplets from coughs and
Initial spike protein priming by transmembrane
sneezes within a range of about 2 metres (6 ft 7
protease, serine 2 (TMPRSS2) is essential for entry
in).Indirect contact via contaminated surfaces is
of SARS-CoV-2. After a SARS-CoV-2 virion
another possible cause of infection. Preliminary
attaches to a target cell, the cell's protease TMPRSS2
research indicates that the virus may remain viable on
cuts open the spike protein of the virus, exposing a
plastic and steel for up to three days, but does not
fusion peptide. The virion then releases RNA into the
survive on cardboard for more than one day or on
cell, forcing the cell to produce copies of the virus
copper for more than four hours, and is inactivated by
that are disseminated to infect more cells.[better
soap.Viral RNA has also been found in stool samples
source needed] SARS-CoV-2 produces at least three
from infected people.
virulence factors that promote shedding of new
1.4. UNCOATING THE VIRUS virions from host cells and inhibit immune response.

Each SARS-CoV-2 virion is approximately 50–


200 nanometres in diameter.Like other
coronaviruses, SARS-CoV-2 has four structural
proteins, known as the S (spike), E (envelope),
M (membrane), and N (nucleocapsid) proteins;
the N protein holds the RNA genome, and the S,
E, and M proteins together create the viral
envelope. The spike protein, which has been
imaged at the atomic level using cryogenic
Fig.3 Corona Population under lungs cells genome.

The new SARS-CoV-2 sequence was compared to


existing genomes using online NCBI BLAST
1.5. Coronavirus Replicate Protein (https://blast.ncbi.nlm.nih.gov/Blast.cgi).
Expression and Processing
The final genome of sequenced SARS-CoV-2
The proteinase activities for all coronaviruses include consists of a single, positive-stranded RNA that is
both papain-like proteinase (PLP) and picornavirus 29,811 nucleotides long, broken down as follows:
3C-like proteinase activities that are encoded within 8,903 (29.86%) adenosines, 5,482 (18.39%)
the replicase polyproteins and mediate both cis and cytosines, 5,852 (19.63%) guanines, and 9,574
trans cleavage events (Ziebuhr et al., 2000). Because (32.12%) thymines.
of the parallel evolution of the proteinases, their
cleavage sites, and the hierarchical cleavage The sequence of BetaCoV/Nepal/61/2020 from
processes, the proteolytic processing of the coordinates 1 to 29811 is identical to the sequence of
coronavirus replicase proteins may serve as distinct isolate Wuhan-Hu-1 (GenBank accession number
regulatory and genetic elements (Ziebuhr et al., NC_045512) from 16 to 29826 (29810/29811),
2001). Specifically, there are both conserved and except at site 24019, with the same substitution of a
divergent regions of the replicase polyproteins by C from isolate Wuhan-Hu-1 for T.
amino acid identity and similarity, with the sequences
The C24019T mutation corresponds to C24034T if
and predicted mature proteins beginning with the 3C-
we use the sequence located under GISAID strain
like proteinases through the carboxy terminus of the
identifier EPI_ISL_405839 as a reference. This was a
replicase polyprotein retaining higher identity and
silent mutation at the spike gene (codon AAC to
similarity across the predicted proteins. In contrast,
AAT). Based on the reference sequence, the
the amino-terminal third of the replicase
following five mutations were also identified:
demonstrates the most variation in proteins, cleavage
T8782C (in ORF1a, codons AGT to AGC, silent
site locations, and the number of proteinases that
mutation), T9561C (in ORF1a, codons TTA to TCA,
mediate maturation processing. SCoV appears to
non silent mutation), C15607T (in ORF1b, codons
have the general organization of, and similar protein
CTA to TTA, silent mutation), C28144T (in ORF8b,
sizes to, the group 2 coronaviruses such as MHV in
codons TCA to TTA, non silent mutation), and
this part of the genome (Snijder et al., 2003).
T29095C (in nucleocapsid, codons TTT to TTC,
However, SCoV likely uses only one PLP to mediate
silent mutation).
the cleavages, similar to the group 3 coronavirus
infectious bronchitis virus (IBV). Thus this region of
1.7. Data availability.
the replicase may experience the most variability,
suggesting either the encoding of accessory functions This sequence has been deposited in GenBank under
that are flexible and tolerant of changes, or the accession number MT072688 and at the GISAID
conversely group or host-specific roles that are EpiCoV newly emerging coronavirus SARS-CoV-2
subject to pressure for more rapid change. platform under identifier EPI_ISL_410301. The
accession numbers for the Illumina MiSeq sequence
1.6. Genetic seqeuencing
raw reads in the NCBI Sequence Read Archive
The new virus responsible for COVID-19 has (SRA) are PRJNA608651 (BioProject),
genomic sequence of 29,811 bp with no gap and high
average coverage (>77,000×). Primer binding sites at
the 5′ and 3′ ends were removed, resulting in this
genome being 59 nucleotides (nt) shorter than a
reference genome in GenBank (accession number
NC_045512), excluding the poly(A) tail of the
Fig 4. 20,2020).
Genome SARS-CoV can be efficiently grown in cell
Code of culture and rapidly spread from person to
person . It can survive in feces and urine at
room temperature for >2 days
(http://www.who.int/csr/sars/en) and may
cause serious, even fatal, disease. SARS-
CoV, a National Institute of Allergy and
Infectious Diseases Biodefense Category C
CoronaVirus priority pathogen
(http://www2.niaid.nih.gov/Biodefense/band
Data taken from ASM journal.”Complete Genome
c_priority.htm) could be used by
Sequence of a 2019 Novel Coronavirus (SARS-
bioterrorists as a biological weapon.
CoV-2) Strain Isolated in Nepal”
Therefore, development of effective and safe
vaccines is urgently needed to prevent a new
SARS epidemic and for biodefense
2. REVIEW LITERATURE preparedness.
As COVID-19 is a new outbreak,obviously Currently, 3 major classes of SARS vaccines
we don’t have any treatment or cure uptil are under development:
now. Researchers all over the world are 1) inactivated SARS-CoV
working on getting the solution to this. we’ll 2) full-length S protein
look to the reference for the general idea for 3) those based on fragments containing
antidote or vaccine , maybe it will not be neutralizing epitopes .
enough for it but it can be the beginning of Another way is the prevention from
it.From the past research ,which have done disease.Though we don’t know the cure ,but
on vaccination for viral disease or anti-viral prevention we know. Many countries all
vaccines,it has seen that curcumin present in over the world has announced the lockdown
turmeric have antiviral properties,for like including India ,USA, Russia,and etc.and
HIV, HCV ,HBV and etc. peoples are strictly advised to follow the
(reference:HIV,Sui et al.1993, Mazumder et quarantine .Patients affected with
al.1995,Barthelemy et al.1998. COVID-19 are kept in isolation and given
HCV:Anggakusuma et al.2014. HBV:Wei et proper care.Increase rate in new cases and
al.2017,kim et al.2009,2011.) Curcumin’s death rate is the matter of concern but world
antiviral properties are yet not discovered health organizations [WHO] and
for COVID-19, but it can be effective if governments ,medical staff and
research is conducted on it.(reference: Lisa services,researchers and investigators all
kirchoff et al.2019) over the world are trying their best.
In Medical Terms,the concept of viral
infections are related and dependent on
immunogenicity."Knowing the
immunogenicity of certain viral regions,
or in other words, which parts of the
virus the immune system reacts to and
how strongly, is of immediate relevance
for the design of promising vaccine
candidates and their evaluation,"
explained principal Investigator
Alessandro Sette, Dr Biol Sci
(reference:kenneth bender et al.March
3. IDEAS OF TREATMENT coronaviruses faces many challenges . First, for
mucosal infections, natural infection does not prevent
Currently, there are no antiviral therapeutics that subsequent infection, and so vaccines must either
specifically target human coronaviruses, so induce better immunity than the original virus or
treatments are only supportive. In vitro, interferons must at least lessen the disease incurred during a
(IFNs) are only partially effective against secondary infection. Second, the propensity of the
coronaviruses . IFNs in combination with ribavirin viruses to recombine may pose a problem by
may have increased activity in vitro when compared rendering the vaccine useless and potentially
to IFNs alone against some coronaviruses; however, increasing the evolution and diversity of the virus in
the effectiveness of this combination requires further the wild . Finally, it has been shown in Fractional
evaluation . The SARS and MERS outbreaks have dose of inactivated poliovirus [ FIPV] that
stimulated research on these viruses and this research vaccination with S protein leads to enhanced disease .
has identified a large number of suitable anti-viral Despite this, several strategies are being developed
targets, such as viral proteases, polymerases, and for vaccine development to reduce the likelihood of
entry proteins. Significant work remains, however, to recombination, for instance by making large deletions
develop drugs that target these processes and are able in the nsp1 or E proteins , rearranging the 3" end of
to inhibit viral replication. the genome , modifying the TRS sequences , or using
mutant viruses with abnormally high mutation rates
We have only limited options for coronavirus.
that significantly attenuate the virus .
Vaccines have only been approved for IBV, TGEV,
and Canine CoV, but these vaccines are not always As we know,that SARS-CoV 2 affects the human
used because they are either not very effective, or in respiratory system,which is directly related to lungs
some cases have been reported to be involved in the and pulmonary body parts,due to which the patients
selection of novel pathogenic CoVs via suffering from disease faces problem in breathing and
recombination of circulating strains. Vaccines for other respiratory functions.Though the vaccines are
veterinary pathogens, such as Porcine epidemic not yet available,but can be made using genetic
diarrhea virus [PEDV], may be useful in such cases material of virus as like vaccine-derived poliovirus
where spread of the virus to a new location could (VDPV), in oral polio vaccine(OPV) contains an
lead to severe losses of veterinary animals. In the attenuated (weakened) vaccine-virus,activating an
case of SARS-CoV, several potential vaccines have immune response in body,like this the vaccine for
been developed but none are yet approved for use. covid-19 can be made.
These vaccines include recombinant attenuated
viruses, live virus vectors, or individual viral proteins
expressed from DNA plasmids. Therapeutic SARS-
CoV neutralizing antibodies have been generated and
could be retrieved and used again in the event of
another SARS-CoV outbreak. Such antibodies would
be most useful for protecting healthcare workers. In
general, it is thought that live attenuated vaccines
would be the most efficacious in targeting
coronaviruses. This was illustrated in the case of
Transmissible gastroenteritis virus [ TGEV], where Fig 6:Strategy for designing vaccines for severe acute
an attenuated variant, Porcine respiratory coronavirus respiratory syndrome (SARS) using inactivated
[ PRCV], appeared in Europe in the 1980s. This SARS-associated coronavirus. This virus expresses
variant only caused mild disease and completely several structural proteins, including nucleocapsid
protected swine from TGEV. Thus, this attenuated (N), membrane (M), envelope (E), and spike (S).
virus has naturally prevented the reoccurrence of
severe TGEV in Europe and the U.S. over the past 30
years . Despite this success, vaccine development for
Another way to stop SARS-CoV in humans is tetracycline.
increase the humoral immunity of humans by
supplements or any medicine,which resists against 2.6. Another way of treatment is to maintain a
the virus. In short, reducing the activity of viruses little higher temperature than normal room
and increasing the strength of immunity. temperature,as the virus is less stable at high
temperature and high humidity.Avoid using
3.1. The curcuminoids were detected as air conditioned places .
curcumin, desmethoxy curcumin, and
bisdesmethoxy curcumin,present in turmeric Owing to the lack of effective therapeutics or
have anti inflammatory effects.Also vaccines, the best measures to control human
turmeric contains curcumin oil,which have coronaviruses remain a strong public health
antibacterial ,antiviral ,antimicrobial and surveillance system coupled with rapid diagnostic
antifungal uses. testing and quarantine when necessary. For
international outbreaks, cooperation of governmental
3.2. In ayurveda,turmeric is said to be a Golden entities, public health authorities and health care
spice which can cure various diseases providers is critical.
including common cold and pneumonia,so
curcumin abstracts can be used to increase CONCLUSION
immunal strength.
The above study concludes the information of human
2.4 In traditional way vaccines,the genetic coronavirus and SARS-CoV-2 ,the past outbreak
material from weakened virus is injected in history and ideas of treatment ,vaccination and
the body so that the immunal cells recognize antidote. We hope it will help in discovering the ideal
it and destroys it,and the other way is to cure or vaccine for COVID-19. 1)An ideal vaccine
insert the modified genetic material into the should be able to deactivate the activities of viruses
body ,so that the immunal cells produce that in the human body. 2)It should be able to provide the
kind of molecule that destroys or disable the immunity strength to the cells of the body.
virus.or by reverse transcripting the genetic 3)Currently many countries all the world have started
material of the virus as it contains single their clinical trials of inactivated COVID -19
stranded RNA as genetic material,by reverse vaccines like USA,China and Russia .4) Recent
transcripting RNA and modifying it into studies have demonstrated that recombinant RBD
double stranded DNA,which will disable the consists of multiple conformational neutralizing
activity of the virus .when this artificially epitopes that induce highly potent neutralizing
modified DNA comes in contact with the antibodies against SARS-CoV (9,26,35–38). Unlike
cells ,the golgi bodies of cell starts to full-length S protein, RBD does not contain
replicate this DNA,so this can reduce or stop immunodominant sites that induce non neutralizing
the activity of SARS-CoV-2. antibodies. RBD sequences are relatively conserved.
Thus, recombinant RBD or vectors encoding RBD
2.5 Antidote can be made from the may be used as safe and efficacious vaccines for
genetic material of animals who don't preventing infection by SARS-CoV with distinct
get affected by SARS-CoV-2,or the genotypes.
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