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CORONA VIRUS
ASIF NAWAZ
Mpill (Microbiology)
AUST
CONTENTS:
 WHAT IS CORONA VIRUS:
 HISTORY
 HUMAN CORONA VIRUS TYPES
 CLASSIFICATION
 EMERGENCE OF THE SEVERE ACUTE
RESPIRATORY
SYNDROME (SARS) CORONAVIRUS
 CORONAVIRUS GENOME AND STRUCTURE
 VIRION STRUCTURE
 PATHOGENESIS
 SYMTOMS
 DIAGNOSIS
 TREATMENT
 REFRENCES
WHAT IS CORONA VIRUS
 Coronaviruses are a family of viruses that cause disease in animals.
Seven, including the new virus, have made the jump to humans, but
most just cause cold-like symptoms.
 Two other coronaviruses – Middle East respiratory syndrome
(Mers) and severe acute respiratory syndrome (Sars) – are much
more severe,
 The new virus, officially called Covid-19, is also dangerous - so far,
around 20 per cent of confirmed cases have been classed as severe
or critical. So far, around 15 to 20 per cent of hospital cases have
been classed as "severe" and the current death rate varies between
0.7 per cent and 3.4 per cent depending on the location and,
crucially, access to good hospital care.
 This is much lower than fatality rates for Mers (30 per cent) and
Sars (10 per cent), but still a significant threat.
HISTORY:
 Coronaviruses were first identified in the 1960s, but
no one knows where they come from.
 In 1965 Tyrrell and Bynoe found a virus named B814.
 It was found in human tracheal organ cultures
obtained from the respiratory tract of an adult with a
common cold.
 Tyrrell and Bynoe were unable to grow the agent in
tissue culture at that time.
 At about the same time, Hamre and Procknow were
able to grow a virus with unusual properties in tissue
culture from samples obtained from medical students
with colds. Both B814 and Hamre's virus, which she
called 229E
HISTORY
 While working in the laboratory of Robert Chanock at the National
Institutes of Health, (McIntosh et al) reported the recovery of
multiple strains of ether-sensitive agents from the human respiratory
tract by using a technique similar to that of Tyrrell and Bynoe.
 These viruses were termed “OC” to designate that they were grown
in organ cultures.
 Within the same time frame, Almeida and Tyrrell performed electron
microscopy on fluids from organ cultures infected with B814 and
found particles that resembled the infectious bronchitis virus of
chickens.
 The particles were medium sized (80–150 nm), pleomorphic,
membrane-coated, and covered with widely spaced club-shaped
surface projections.
 The 229E agent identified by Hamre and Procknow and the
previous OC viruses identified by (McIntosh et al) had a similar
morphology .
HUMAN CORONA VIRUS TYPES
 Coronaviruses are named for the crown-like spikes on their
surface.
 There are four main sub-groups of coronaviruses, known as alpha,
beta, gamma, and delta.
 Common human coronaviruses:
229E (alpha coronavirus)
NL63 (alpha coronavirus)
OC43 (beta coronavirus)
HKU1 (beta coronavirus)
 Other human coronaviruses:
MERS-CoV (the beta coronavirus that causes Middle East
Respiratory Syndrome, or MERS).
SARS-CoV (the beta coronavirus that causes severe acute
respiratory syndrome, or SARS).
 SARS-CoV-2 (the novel coronavirus that causes coronavirus
disease 2019, or COVID-19.
CLASSIFICATION
 Coronaviruses (CoVs) are the largest group of viruses
belonging to the Nidovirales order, which
includes Coronaviridae, Arteriviridae, and
Roniviridae families.
 The Coronavirinae comprise one of two subfamilies in
the Coronaviridae family, with the other being
the Torovirinae. The Coronavirinae are further subdivided
into four groups, the alpha, beta, gamma and delta
coronaviruses.
 The viruses were initially sorted into these groups based on
serology but are now divided by phylogenetic clustering.
 All viruses in the Nidovirales order are enveloped, non-
segmented positive-sense RNA viruses.
 They all contain very large genomes for RNA viruses,
with Coronavirinae having the largest identified RNA
genomes, containing approximately 30 kilobase (kb)
CLASSIFICATION
 Other common features within the Nidovirales order
include: i) a highly conserved genomic organization,
with a large replicase gene preceding structural and
accessory genes; ii) expression of many nonstructural
genes by ribosomal frameshifting; iii) several unique or
unusual enzymatic activities encoded within the large
replicase-transcriptase polyprotein; and iv) expression
of downstream genes by synthesis of 3′ nested sub-
genomic mRNAs.
 In fact, the Nidovirales order name is derived from
these nested 3′ mRNAs as nido is Latin for “nest”. The
major differences within the Nidovirus families are in
the number, type, and sizes of the structural proteins.
These differences cause significant alterations in the
structure and morphology of the nucleocapsids and
virions.
EMERGENCE OF THE SEVERE ACUTE
RESPIRATORY SYNDROME (SARS) CORONAVIRUS
 Given the enormous variety of animal coronaviruses, it was not
surprising when the cause of a very new, severe acute respiratory
syndrome, called SARS, emerged in 2002–2003 as
a coronavirus from southern China and spread throughout the world
with quantifiable speed.
 This virus grew fairly easily in tissue culture, enabling quick
sequencing of the genome. Sequencing differed sufficiently from any
of the known human or animal coronaviruses to place this virus into a
new group.
 During the 2002–2003 outbreak, SARS infection was reported in 29
countries in North America, South America, Europe and Asia.
 Overall 8098 infected individuals were identified, with 774 SARS-
related fatalities. It is still unclear how the virus entered the human
population
CORONAVIRUS GENOME AND STRUCTURE
 Coronaviruses are medium-sized RNA viruses with a
very characteristic appearance in electron micrographs of
negatively stained preparations .
 The nucleic acid is about 30 kb long, positive in sense,
single stranded and polyadenylated.
 The RNA is the largest known viral RNA and codes for a
large polyprotein. This polyprotein is cleaved by viral-
encoded proteases to form the following: an RNA-
dependent RNA polymerase and an ATPase helicase; a
surface hemagglutinin-esterase protein present on OC43
and several other group II coronaviruses; the large
surface glycoprotein (S protein) that forms the petal-
shaped surface projections; a small envelope protein (E
protein); a membrane glycoprotein (M protein); and a
nucleocapsid protein (N protein) that forms a complex
with the RNA.
CORONAVIRUS GENOME AND STRUCTURE
 The coding functions of several other ORFs are not
clear.
 The strategy of replication of coronaviruses involves a
nested set of messenger RNAs with common
polyadenylated 3-ends.
 Only the unique portion of the 5-end is translated.
 Mutations are common in nature. In addition,
coronaviruses are capable of genetic recombination if
2 viruses infect the same cell at the same time.
 All coronaviruses develop in the cytoplasm of infected
cells , budding into cytoplasmic vesicles from the
endoplasmic reticulum.
 These vesicles are either extruded or released from the
cell within the same time frame, and then the cell is
destroyed.
VIRION STRUCTURE
 Coronavirus virions are spherical with diameters of
approximately 125 nm as depicted in recent studies by
cryo-electron tomography and cryo-electron microscopy .
 The most prominent feature of coronaviruses is the club-
shape spike projections emanating from the surface of the
virion.
 These spikes are a defining feature of the virion and give
them the appearance of a solar corona, prompting the
name, coronaviruses. Within the envelope of the virion is
the nucleocapsid.
 Coronaviruses have helically symmetrical nucleocapsids,
which is uncommon among positive-sense RNA viruses,
but far more common for negative-sense RNA viruses.
PATHOGENESIS
 Studies in both organ cultures and human
volunteers show that coronaviruses are
extremely fastidious and grow only in
differentiated respiratory epithelial cells.
 Infected cells become vacuolated, show
damaged cilia, and may form syncytia.
 Cell damage triggers the production of
inflammatory mediators, which increase nasal
secretion and cause local inflammation and
swelling.
 These responses in turn stimulate sneezing,
obstruct the airway, and raise the temperature
of the mucosa.
SYMTOMS
Diagnosis
 Diagnosis of corona virus includes:
 Rapid Diagnostic Devices
 RT- Pcr
 Sputum analysis
 Deep throat Swabs
 Colds caused by coronaviruses cannot be distinguished
clinically from other colds in any one individual. Laboratory
diagnosis may be made on the basis of antibody titers in paired
sera.
 The virus is difficult to isolate. Nucleic acid hybridization tests
(including PCR) are now being introduced.
TREATMENT
 To date, there are no anti-viral therapeutics that specifically target human coronaviruses, so treatments are only
supportive.
 In vitro, interferons (IFNs) are only partially effective against coronaviruses .
 IFNs in combination with ribavirin may have increased activity in vitro when compared to IFNs alone against
some coronaviruses; however, the effectiveness of this combination in vivo requires further evaluation .
 The SARS and MERS outbreaks have stimulated research on these viruses and this research has identified a large
number of suitable anti-viral targets, such as viral proteases, polymerases, and entry proteins. Significant work
remains, however, to develop drugs that target these processes and are able to inhibit viral replication.
 Only limited options are available to prevent coronavirus infections. Vaccines have only been approved for IBV,
TGEV, and Canine CoV, but these vaccines are not always used because they are either not very effective, or in
some cases have been reported to be involved in the selection of novel pathogenic CoVs via recombination of
circulating strains. Vaccines for veterinary pathogens, such as PEDV, may be useful in such cases where spread of
the virus to a new location could lead to severe losses of veterinary animals. In the case of SARS-CoV, several
potential vaccines have been developed but none are yet approved for use. These vaccines include recombinant
attenuated viruses, live virus vectors, or individual viral proteins expressed from DNA plasmids.
REFRENCES
 Zhao L, Jha BK, Wu A, Elliott R, Ziebuhr J, Gorbalenya AE, Silverman RH, Weiss
SR. Antagonism of the interferon-induced OAS-RNase L pathway by murine
coronavirus ns2 protein is required for virus replication and liver
pathology. Cell host & microbe. 2012;11(6):607–616. [PMC free
article] [PubMed] [Google Scholar]
 2. Barcena M, Oostergetel GT, Bartelink W, Faas FG, Verkleij A, Rottier PJ,
Koster AJ, Bosch BJ. Cryo-electron tomography of mouse hepatitis virus:
Insights into the structure of the coronavirion. Proceedings of the National
Academy of Sciences of the United States of America. 2009;106(2):582–
587. [PMC free article] [PubMed] [Google Scholar]
 3. Neuman BW, Adair BD, Yoshioka C, Quispe JD, Orca G, Kuhn P, Milligan RA,
Yeager M, Buchmeier MJ. Supramolecular architecture of severe acute
respiratory syndrome coronavirus revealed by electron
cryomicroscopy. Journal of virology. 2006;80(16):7918–7928. [PMC free
article] [PubMed] [Google Scholar]
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369385/
WWW.SLIDESHARE.NET/ASIFNAWAZALIZAI

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Corona virus brief introduction

  • 1.
  • 2. CORONA VIRUS ASIF NAWAZ Mpill (Microbiology) AUST
  • 3. CONTENTS:  WHAT IS CORONA VIRUS:  HISTORY  HUMAN CORONA VIRUS TYPES  CLASSIFICATION  EMERGENCE OF THE SEVERE ACUTE RESPIRATORY SYNDROME (SARS) CORONAVIRUS  CORONAVIRUS GENOME AND STRUCTURE  VIRION STRUCTURE  PATHOGENESIS  SYMTOMS  DIAGNOSIS  TREATMENT  REFRENCES
  • 4. WHAT IS CORONA VIRUS  Coronaviruses are a family of viruses that cause disease in animals. Seven, including the new virus, have made the jump to humans, but most just cause cold-like symptoms.  Two other coronaviruses – Middle East respiratory syndrome (Mers) and severe acute respiratory syndrome (Sars) – are much more severe,  The new virus, officially called Covid-19, is also dangerous - so far, around 20 per cent of confirmed cases have been classed as severe or critical. So far, around 15 to 20 per cent of hospital cases have been classed as "severe" and the current death rate varies between 0.7 per cent and 3.4 per cent depending on the location and, crucially, access to good hospital care.  This is much lower than fatality rates for Mers (30 per cent) and Sars (10 per cent), but still a significant threat.
  • 5. HISTORY:  Coronaviruses were first identified in the 1960s, but no one knows where they come from.  In 1965 Tyrrell and Bynoe found a virus named B814.  It was found in human tracheal organ cultures obtained from the respiratory tract of an adult with a common cold.  Tyrrell and Bynoe were unable to grow the agent in tissue culture at that time.  At about the same time, Hamre and Procknow were able to grow a virus with unusual properties in tissue culture from samples obtained from medical students with colds. Both B814 and Hamre's virus, which she called 229E
  • 6. HISTORY  While working in the laboratory of Robert Chanock at the National Institutes of Health, (McIntosh et al) reported the recovery of multiple strains of ether-sensitive agents from the human respiratory tract by using a technique similar to that of Tyrrell and Bynoe.  These viruses were termed “OC” to designate that they were grown in organ cultures.  Within the same time frame, Almeida and Tyrrell performed electron microscopy on fluids from organ cultures infected with B814 and found particles that resembled the infectious bronchitis virus of chickens.  The particles were medium sized (80–150 nm), pleomorphic, membrane-coated, and covered with widely spaced club-shaped surface projections.  The 229E agent identified by Hamre and Procknow and the previous OC viruses identified by (McIntosh et al) had a similar morphology .
  • 7. HUMAN CORONA VIRUS TYPES  Coronaviruses are named for the crown-like spikes on their surface.  There are four main sub-groups of coronaviruses, known as alpha, beta, gamma, and delta.  Common human coronaviruses: 229E (alpha coronavirus) NL63 (alpha coronavirus) OC43 (beta coronavirus) HKU1 (beta coronavirus)  Other human coronaviruses: MERS-CoV (the beta coronavirus that causes Middle East Respiratory Syndrome, or MERS). SARS-CoV (the beta coronavirus that causes severe acute respiratory syndrome, or SARS).  SARS-CoV-2 (the novel coronavirus that causes coronavirus disease 2019, or COVID-19.
  • 8. CLASSIFICATION  Coronaviruses (CoVs) are the largest group of viruses belonging to the Nidovirales order, which includes Coronaviridae, Arteriviridae, and Roniviridae families.  The Coronavirinae comprise one of two subfamilies in the Coronaviridae family, with the other being the Torovirinae. The Coronavirinae are further subdivided into four groups, the alpha, beta, gamma and delta coronaviruses.  The viruses were initially sorted into these groups based on serology but are now divided by phylogenetic clustering.  All viruses in the Nidovirales order are enveloped, non- segmented positive-sense RNA viruses.  They all contain very large genomes for RNA viruses, with Coronavirinae having the largest identified RNA genomes, containing approximately 30 kilobase (kb)
  • 9. CLASSIFICATION  Other common features within the Nidovirales order include: i) a highly conserved genomic organization, with a large replicase gene preceding structural and accessory genes; ii) expression of many nonstructural genes by ribosomal frameshifting; iii) several unique or unusual enzymatic activities encoded within the large replicase-transcriptase polyprotein; and iv) expression of downstream genes by synthesis of 3′ nested sub- genomic mRNAs.  In fact, the Nidovirales order name is derived from these nested 3′ mRNAs as nido is Latin for “nest”. The major differences within the Nidovirus families are in the number, type, and sizes of the structural proteins. These differences cause significant alterations in the structure and morphology of the nucleocapsids and virions.
  • 10. EMERGENCE OF THE SEVERE ACUTE RESPIRATORY SYNDROME (SARS) CORONAVIRUS  Given the enormous variety of animal coronaviruses, it was not surprising when the cause of a very new, severe acute respiratory syndrome, called SARS, emerged in 2002–2003 as a coronavirus from southern China and spread throughout the world with quantifiable speed.  This virus grew fairly easily in tissue culture, enabling quick sequencing of the genome. Sequencing differed sufficiently from any of the known human or animal coronaviruses to place this virus into a new group.  During the 2002–2003 outbreak, SARS infection was reported in 29 countries in North America, South America, Europe and Asia.  Overall 8098 infected individuals were identified, with 774 SARS- related fatalities. It is still unclear how the virus entered the human population
  • 11. CORONAVIRUS GENOME AND STRUCTURE  Coronaviruses are medium-sized RNA viruses with a very characteristic appearance in electron micrographs of negatively stained preparations .  The nucleic acid is about 30 kb long, positive in sense, single stranded and polyadenylated.  The RNA is the largest known viral RNA and codes for a large polyprotein. This polyprotein is cleaved by viral- encoded proteases to form the following: an RNA- dependent RNA polymerase and an ATPase helicase; a surface hemagglutinin-esterase protein present on OC43 and several other group II coronaviruses; the large surface glycoprotein (S protein) that forms the petal- shaped surface projections; a small envelope protein (E protein); a membrane glycoprotein (M protein); and a nucleocapsid protein (N protein) that forms a complex with the RNA.
  • 12. CORONAVIRUS GENOME AND STRUCTURE  The coding functions of several other ORFs are not clear.  The strategy of replication of coronaviruses involves a nested set of messenger RNAs with common polyadenylated 3-ends.  Only the unique portion of the 5-end is translated.  Mutations are common in nature. In addition, coronaviruses are capable of genetic recombination if 2 viruses infect the same cell at the same time.  All coronaviruses develop in the cytoplasm of infected cells , budding into cytoplasmic vesicles from the endoplasmic reticulum.  These vesicles are either extruded or released from the cell within the same time frame, and then the cell is destroyed.
  • 13. VIRION STRUCTURE  Coronavirus virions are spherical with diameters of approximately 125 nm as depicted in recent studies by cryo-electron tomography and cryo-electron microscopy .  The most prominent feature of coronaviruses is the club- shape spike projections emanating from the surface of the virion.  These spikes are a defining feature of the virion and give them the appearance of a solar corona, prompting the name, coronaviruses. Within the envelope of the virion is the nucleocapsid.  Coronaviruses have helically symmetrical nucleocapsids, which is uncommon among positive-sense RNA viruses, but far more common for negative-sense RNA viruses.
  • 14. PATHOGENESIS  Studies in both organ cultures and human volunteers show that coronaviruses are extremely fastidious and grow only in differentiated respiratory epithelial cells.  Infected cells become vacuolated, show damaged cilia, and may form syncytia.  Cell damage triggers the production of inflammatory mediators, which increase nasal secretion and cause local inflammation and swelling.  These responses in turn stimulate sneezing, obstruct the airway, and raise the temperature of the mucosa.
  • 16. Diagnosis  Diagnosis of corona virus includes:  Rapid Diagnostic Devices  RT- Pcr  Sputum analysis  Deep throat Swabs  Colds caused by coronaviruses cannot be distinguished clinically from other colds in any one individual. Laboratory diagnosis may be made on the basis of antibody titers in paired sera.  The virus is difficult to isolate. Nucleic acid hybridization tests (including PCR) are now being introduced.
  • 17. TREATMENT  To date, there are no anti-viral therapeutics that specifically target human coronaviruses, so treatments are only supportive.  In vitro, interferons (IFNs) are only partially effective against coronaviruses .  IFNs in combination with ribavirin may have increased activity in vitro when compared to IFNs alone against some coronaviruses; however, the effectiveness of this combination in vivo requires further evaluation .  The SARS and MERS outbreaks have stimulated research on these viruses and this research has identified a large number of suitable anti-viral targets, such as viral proteases, polymerases, and entry proteins. Significant work remains, however, to develop drugs that target these processes and are able to inhibit viral replication.  Only limited options are available to prevent coronavirus infections. Vaccines have only been approved for IBV, TGEV, and Canine CoV, but these vaccines are not always used because they are either not very effective, or in some cases have been reported to be involved in the selection of novel pathogenic CoVs via recombination of circulating strains. Vaccines for veterinary pathogens, such as PEDV, may be useful in such cases where spread of the virus to a new location could lead to severe losses of veterinary animals. In the case of SARS-CoV, several potential vaccines have been developed but none are yet approved for use. These vaccines include recombinant attenuated viruses, live virus vectors, or individual viral proteins expressed from DNA plasmids.
  • 18. REFRENCES  Zhao L, Jha BK, Wu A, Elliott R, Ziebuhr J, Gorbalenya AE, Silverman RH, Weiss SR. Antagonism of the interferon-induced OAS-RNase L pathway by murine coronavirus ns2 protein is required for virus replication and liver pathology. Cell host & microbe. 2012;11(6):607–616. [PMC free article] [PubMed] [Google Scholar]  2. Barcena M, Oostergetel GT, Bartelink W, Faas FG, Verkleij A, Rottier PJ, Koster AJ, Bosch BJ. Cryo-electron tomography of mouse hepatitis virus: Insights into the structure of the coronavirion. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(2):582– 587. [PMC free article] [PubMed] [Google Scholar]  3. Neuman BW, Adair BD, Yoshioka C, Quispe JD, Orca G, Kuhn P, Milligan RA, Yeager M, Buchmeier MJ. Supramolecular architecture of severe acute respiratory syndrome coronavirus revealed by electron cryomicroscopy. Journal of virology. 2006;80(16):7918–7928. [PMC free article] [PubMed] [Google Scholar]  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369385/
  • 19.