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HUMAN CORONA VIRUSES
PRESENTED BY: HAFIZA FATEHA FAREED
M.Sc Clinical
Dated: 4th April 2020
COVID 19
 Corona viruses (CoV) are a large family of viruses that causes illness from the
common cold to more severe diseases such as Middle East Respiratory Syndrome
(MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). A Novel
Coronavirus (nCoV) is a new strain that has not been previously identified in
humans,
 Corona viruses are zoonotic, meaning they are transmitted between animals and
people.
 Common signs of infection include
 Respiratory symptoms
 Fever
 Cough
 Shortness of breath
 In more severe cases, infection can cause pneumonia, severe acute respiratory
syndrome, renal failure and even death.
 When a disease is new as COVID 19 there is usually no vaccine until one is
developed it can even take a number of years for a new vaccine to be developed.
CORONA VIRUL GENOME STRUCTURE AND
REPLICATION:
 CoVs belong to the subfamily Coronavirinae in the family of Coronaviridae of
the order Nidovirales, and this subfamily includes four
genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus,
and Deltacoronavirus.
 The genome of CoVs is a single‐stranded positive‐sense RNA (+ssRNA) (~30 kb)
with 5′‐cap structure and 3′‐poly‐A tail.
 The genomic RNA is used as template to directly translate polyprotein 1a/1ab
(pp1a/pp1ab), which encodes nonstructural proteins (nsps) to form the
replication‐transcription complex (RTC) in a double‐membrane vesicles
(DMVs).
 Subsequently, a nested set of subgenomic RNAs (sgRNAs) are synthesized by
RTC in a manner of discontinuous transcription.
CONTD
 These subgenomic messenger RNAs (mRNAs) possess common 5′‐leader and
3′‐terminal sequences. Transcription termination and subsequent acquisition of a
leader RNA occurs at transcription regulatory sequences, located between open
reading frames (ORFs). These minus‐strand sgRNAs serve as the templates for
the production of subgenomic mRNAs.
FUNCTIONS OF NONSTRUCTURAL AND
STRUCTURAL PROTEINS IN CORONAVIRAL
REPLICATION:
 Most of the nsps of nsp1‐16 have been
reported for their specific roles in the
replication of CoVs. However, the functions
of some of the nsps are unknown or not
well understood. The known functions of
the 16 nsps are summarized in Table
nsps Functions References
nsp1 Cellular mRNA degradation,
inhibiting IFN signaling
15, 16
nsp2 Unknown 17, 18
nsp3 PLP, polypeptides cleaving,
blocking host innate immune
response, promoting cytokine
expression
19, 20
nsp4 DMV formation 21, 22
nsp5 3CL
pro
, M
pro
, polypeptides
cleaving, inhibiting IFN signaling
23-25
nsp6 Restricting autophagosome
expansion, DMV formation
26, 27
nsp7 Cofactor with nsp8 and nsp12 28, 29
nsp8 Cofactor with nsp7 and nsp12,
primase
28-30
nsp9 Dimerization and RNA binding 31, 32
nsp10 Scaffold protein for nsp14 and
nsp16
33-36
nsp11 Unknown 37
nsp12 Primer dependent RdRp 28, 38, 39
nsp13 RNA helicase, 5′ triphosphatase 40-42
nsp14 Exoribonuclease, N7‐MTase 12, 43-45
nsp15 Endoribonuclease, evasion of
dsRNA sensors
46-48
DIVERSITY OF CoV PATHOGENESIS:
 Different CoVs display diverse host range and tissue tropism.
Usually, alphacoronaviruses and betacoronaviruses infect mammals. In
contrast, gammacoronaviruses and deltacoronaviruses infect birds
and fish, but some of them can also infect mammals.
 Before 2019, there were only six CoVs that were known to infect human and
cause respiratory diseases. HCoV‐229E, HCoV‐OC43, HCoV‐NL63, and HKU1
cause only mild upper respiratory disease, and in rare cases some of them can
cause severe infection in infants, young children and elders. SARS‐CoV and
MERS‐CoV can infect lower respiratory tract and cause severe respiratory
syndrome in human.
 The new CoV, 2019‐nCoV, which belongs to betacoronaviruses based on
sequence analysis can also infect the lower respiratory tract and cause
pneumonia in human, but it seems that the symptoms are milder than SARS
and MERS. Up to 20 January 2020, 291 cases in total have been confirmed in
China by sequence analysis, clinical diagnosis and epidemiological
examination, including 270 cases in Wuhan and 21 cases in Beijing, Shanghai,
and Guangdong.
List of important pathogenic coronaviruses
Virus Genus Host Symptoms
Human CoV‐229E Alpha Human Mild respiratory tract
infections
Human CoV‐NL63 Alpha Human Mild respiratory tract
infections
PRCV/ISU‐1 Alpha Pig Mild respiratory tract
infections
TGEV/PUR46‐MAD Alpha Pig Diarrhea, with 100% mortality
in piglets less than 2‐wk‐old
PEDV/ZJU‐G1‐2013 Alpha Pig Severe watery diarrhea
SeACoV‐CH/GD‐01 Alpha Pig Severe and acute diarrhea
and acute vomiting
Canine CoV/TU336/F/2008 Alpha Dog Mild clinical signs, diarrhea
Camel alphacoronavirus
isolate camel/Riyadh
Alpha Camel Asymptomatic
Feline infectious peritonitis
virus
Alpha Cat Fever, vasculitis, and
serositis, with or without
effusions
Human CoV‐HKU1 Beta Human Pneumonia
Human CoV‐OC43 Beta Human Mild respiratory tract
infections
SARS‐CoV Beta Human Severe acute respiratory
syndrome, 10% mortality
rate
MERS‐CoV Beta Human Severe acute respiratory
syndrome, 37% mortality
rate
Bovine CoV/ENT Beta Cow Diarrhea
Equine CoV/Obihiro12‐1 Beta Horse Fever, anorexia,
leucopenia
MHV‐A59 Beta Mouse Acute pneumonia and
severe lung injuries
Beluga Whale CoV/SW1 Gamma Whale Pulmonary disease,
terminal acute liver
failure
IBV Gamma Chicken Severe respiratory
disease
Bulbul coronavirus HKU11 Delta Bulbul Respiratory disease
(collected from
respiratory tract of dead
wild birds)
Sparrow coronavirus
HKU17
Delta Sparrow Respiratory disease
(collected from
respiratory tract of dead
wild birds)
EPIDEMIOLOGY:
 As of March 3, 2020, the WHO has confirmed 87,317 cases worldwide. Of
these confirmed cases, 2,977 (3.42%) patients have succumbed to the virus.
 The majority of cases and deaths have been reported in China. Of the total
number of cases, 79,968 (92%) patients have been identified in China.
Likewise, the majority of fatalities (2,873 [96.5%]) have also been reported in
China.
 Outside China, a total of 7,169 cases have emerged in 59 countries. Due to
the ongoing nature of the pandemic, the number of cases and involved
countries are expected to vary.
Location Confirmed
Cases per
1M people
Recovered Deaths
Worldwide 1,141,190 146.76 235,775 60,960
Pakistan 2,708 12.36 130 41
United States 288,923 876.7 9,920 7,158
Spain 124,736 2,648.3 34,219 11,814
Italy 124,632 2,068.81 20,996 15,362
Germany 92,155 1,108.31 14,361 1,300
China 81,639 58.23 76,751 3,326
France 64,338 959.18 14,008 6,507
Iran 55,743 668.93 17,935 3,452
United
Kingdom
41,903 630.73 — 4,313
Turkey 20,921 251.59 484 425
Switzerland 19,985 2,327.48 5,657 637
Belgium 18,431 1,599.29 3,247 1,283
Netherlands 16,627 952.78 — 1,651
Canada 12,906 339.82 2,518 214
Austria 11,679 1,311.86 2,507 186
Portugal 10,524 1,024.07 75 266
South Korea 10,156 196.14 6,325 177
Brazil 9,216 43.61 127 365
Israel 7,589 826.69 427 42
Sweden 6,558 634.64 205 391
Australia 5,550 216.24 636 30
Norway 5,548 1,033.61 — 62
Russia 4,731 32.24 333 43
Ireland 4,273 868.23 10 120
Czechia 4,194 392.18 74 56
Denmark 4,077 700.18 1,283 1
Chile 3,737 195.58 427 22
Poland 3,627 94.5 116 79
Romania 3,613 186.19 329 141
Malaysia 3,483 106.39 915 57
Ecuador 3,465 198.49 65 172
Philippines 3,094 28.52 57 144
India 3,072 2.26 213 75
Japan 2,935 23.3 514 69
Luxembourg 2,612 4,254.81 80 31
Saudi Arabia 2,179 63.68 420 29
Indonesia 2,092 7.84 150 191
Thailand 2,067 31.09 612 20
Finland 1,875 339.21 — 25
Mexico 1,688 13.34 634 60
Panama 1,673 396.56 13 41
Serbia 1,624 233.21 54 44
Greece 1,613 150.4 53 67
Peru 1,595 49.64 537 61
South Africa 1,505 25.61 31 5
United Arab
Emirates
1,505 152.17 125 10
Dominican
Republic
1,488 143.65 16 68
Iceland 1,364 3,744.58 336 4
Argentina 1,353 30.11 248 42
Colombia 1,267 25.65 55 25
Algeria 1,251 29.09 90 130
Singapore 1,189 208.46 297 6
Croatia 1,126 276.23 119 12
Ukraine 1,096 26.17 23 28
Qatar 1,075 391.3 93 3
Estonia 1,018 766.36 59 13
Egypt 985 9.83 216 66
Slovenia 934 446.02 10 20
Iraq 878 22.44 259 56
Hong Kong 862 114.92 173 4
Morocco 858 23.93 62 50
New Zealand 824 165.63 127 1
Lithuania 771 276 7 9
Armenia 770 260.36 43 7
Moldova 752 280.42 29 12
Bahrain 688 445.8 399 4
Hungary 678 69.38 58 32
Bosnia and Herzegovina 617 186.91 28 19
Kazakhstan 525 28.11 36 5
Azerbaijan 521 51.75 32 5
Lebanon 520 76.19 50 17
Cameroon 509 19.17 17 8
Latvia 509 266.94 1 1
Bulgaria 498 71.14 34 14
Tunisia 495 42.23 5 18
North Macedonia 483 232.53 20 17
Andorra 466 6,009.57 21 17
Slovakia 450 82.47 7 1
Belarus 440 46.74 41 5
Kuwait 417 94.34 82 0
Costa Rica 416 82.25 11 2
Cyprus 386 440.69 18 10
Uruguay 386 109.7 86 4
Taiwan 355 15.04 50 5
TREATMENT AND PREVENTION:
 At present, there is no single specific antiviral therapy for CoV and the main
treatments are supportive.
 Recombinant IFN with ribavirin only has limited effects against CoVs
infection.
 After SARS and MERS epidemics, great efforts have been devoted to
development of new antivirals targeting CoVs proteases, polymerases,
MTases, and entry proteins, however, none of them has been shown to be
efficacious in clinical trials.
 Plasma and antibodies obtained from the convalescent patients have been
proposed for use in treatment.
 Since there is no effective therapy or vaccine, the best measures now are to
control the source of infection, early diagnosis, reporting, isolation,
supportive treatments, and timely publishing epidemic information to avoid
unnecessary panic. For individuals, good personal hygiene, fitted mask,
ventilation, and avoiding crowded places will help to prevent CoVs infection.

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HUMAN CORONA VIRUSES.pptx

  • 1. HUMAN CORONA VIRUSES PRESENTED BY: HAFIZA FATEHA FAREED M.Sc Clinical Dated: 4th April 2020
  • 2. COVID 19  Corona viruses (CoV) are a large family of viruses that causes illness from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). A Novel Coronavirus (nCoV) is a new strain that has not been previously identified in humans,  Corona viruses are zoonotic, meaning they are transmitted between animals and people.  Common signs of infection include  Respiratory symptoms  Fever  Cough  Shortness of breath  In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, renal failure and even death.  When a disease is new as COVID 19 there is usually no vaccine until one is developed it can even take a number of years for a new vaccine to be developed.
  • 3. CORONA VIRUL GENOME STRUCTURE AND REPLICATION:  CoVs belong to the subfamily Coronavirinae in the family of Coronaviridae of the order Nidovirales, and this subfamily includes four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus.  The genome of CoVs is a single‐stranded positive‐sense RNA (+ssRNA) (~30 kb) with 5′‐cap structure and 3′‐poly‐A tail.  The genomic RNA is used as template to directly translate polyprotein 1a/1ab (pp1a/pp1ab), which encodes nonstructural proteins (nsps) to form the replication‐transcription complex (RTC) in a double‐membrane vesicles (DMVs).  Subsequently, a nested set of subgenomic RNAs (sgRNAs) are synthesized by RTC in a manner of discontinuous transcription. CONTD
  • 4.  These subgenomic messenger RNAs (mRNAs) possess common 5′‐leader and 3′‐terminal sequences. Transcription termination and subsequent acquisition of a leader RNA occurs at transcription regulatory sequences, located between open reading frames (ORFs). These minus‐strand sgRNAs serve as the templates for the production of subgenomic mRNAs.
  • 5. FUNCTIONS OF NONSTRUCTURAL AND STRUCTURAL PROTEINS IN CORONAVIRAL REPLICATION:  Most of the nsps of nsp1‐16 have been reported for their specific roles in the replication of CoVs. However, the functions of some of the nsps are unknown or not well understood. The known functions of the 16 nsps are summarized in Table
  • 6. nsps Functions References nsp1 Cellular mRNA degradation, inhibiting IFN signaling 15, 16 nsp2 Unknown 17, 18 nsp3 PLP, polypeptides cleaving, blocking host innate immune response, promoting cytokine expression 19, 20 nsp4 DMV formation 21, 22 nsp5 3CL pro , M pro , polypeptides cleaving, inhibiting IFN signaling 23-25 nsp6 Restricting autophagosome expansion, DMV formation 26, 27 nsp7 Cofactor with nsp8 and nsp12 28, 29 nsp8 Cofactor with nsp7 and nsp12, primase 28-30 nsp9 Dimerization and RNA binding 31, 32 nsp10 Scaffold protein for nsp14 and nsp16 33-36 nsp11 Unknown 37 nsp12 Primer dependent RdRp 28, 38, 39 nsp13 RNA helicase, 5′ triphosphatase 40-42 nsp14 Exoribonuclease, N7‐MTase 12, 43-45 nsp15 Endoribonuclease, evasion of dsRNA sensors 46-48
  • 7. DIVERSITY OF CoV PATHOGENESIS:  Different CoVs display diverse host range and tissue tropism. Usually, alphacoronaviruses and betacoronaviruses infect mammals. In contrast, gammacoronaviruses and deltacoronaviruses infect birds and fish, but some of them can also infect mammals.  Before 2019, there were only six CoVs that were known to infect human and cause respiratory diseases. HCoV‐229E, HCoV‐OC43, HCoV‐NL63, and HKU1 cause only mild upper respiratory disease, and in rare cases some of them can cause severe infection in infants, young children and elders. SARS‐CoV and MERS‐CoV can infect lower respiratory tract and cause severe respiratory syndrome in human.  The new CoV, 2019‐nCoV, which belongs to betacoronaviruses based on sequence analysis can also infect the lower respiratory tract and cause pneumonia in human, but it seems that the symptoms are milder than SARS and MERS. Up to 20 January 2020, 291 cases in total have been confirmed in China by sequence analysis, clinical diagnosis and epidemiological examination, including 270 cases in Wuhan and 21 cases in Beijing, Shanghai, and Guangdong.
  • 8. List of important pathogenic coronaviruses Virus Genus Host Symptoms Human CoV‐229E Alpha Human Mild respiratory tract infections Human CoV‐NL63 Alpha Human Mild respiratory tract infections PRCV/ISU‐1 Alpha Pig Mild respiratory tract infections TGEV/PUR46‐MAD Alpha Pig Diarrhea, with 100% mortality in piglets less than 2‐wk‐old PEDV/ZJU‐G1‐2013 Alpha Pig Severe watery diarrhea SeACoV‐CH/GD‐01 Alpha Pig Severe and acute diarrhea and acute vomiting Canine CoV/TU336/F/2008 Alpha Dog Mild clinical signs, diarrhea Camel alphacoronavirus isolate camel/Riyadh Alpha Camel Asymptomatic Feline infectious peritonitis virus Alpha Cat Fever, vasculitis, and serositis, with or without effusions Human CoV‐HKU1 Beta Human Pneumonia Human CoV‐OC43 Beta Human Mild respiratory tract infections
  • 9. SARS‐CoV Beta Human Severe acute respiratory syndrome, 10% mortality rate MERS‐CoV Beta Human Severe acute respiratory syndrome, 37% mortality rate Bovine CoV/ENT Beta Cow Diarrhea Equine CoV/Obihiro12‐1 Beta Horse Fever, anorexia, leucopenia MHV‐A59 Beta Mouse Acute pneumonia and severe lung injuries Beluga Whale CoV/SW1 Gamma Whale Pulmonary disease, terminal acute liver failure IBV Gamma Chicken Severe respiratory disease Bulbul coronavirus HKU11 Delta Bulbul Respiratory disease (collected from respiratory tract of dead wild birds) Sparrow coronavirus HKU17 Delta Sparrow Respiratory disease (collected from respiratory tract of dead wild birds)
  • 10. EPIDEMIOLOGY:  As of March 3, 2020, the WHO has confirmed 87,317 cases worldwide. Of these confirmed cases, 2,977 (3.42%) patients have succumbed to the virus.  The majority of cases and deaths have been reported in China. Of the total number of cases, 79,968 (92%) patients have been identified in China. Likewise, the majority of fatalities (2,873 [96.5%]) have also been reported in China.  Outside China, a total of 7,169 cases have emerged in 59 countries. Due to the ongoing nature of the pandemic, the number of cases and involved countries are expected to vary.
  • 11. Location Confirmed Cases per 1M people Recovered Deaths Worldwide 1,141,190 146.76 235,775 60,960 Pakistan 2,708 12.36 130 41 United States 288,923 876.7 9,920 7,158 Spain 124,736 2,648.3 34,219 11,814 Italy 124,632 2,068.81 20,996 15,362 Germany 92,155 1,108.31 14,361 1,300 China 81,639 58.23 76,751 3,326 France 64,338 959.18 14,008 6,507 Iran 55,743 668.93 17,935 3,452
  • 12. United Kingdom 41,903 630.73 — 4,313 Turkey 20,921 251.59 484 425 Switzerland 19,985 2,327.48 5,657 637 Belgium 18,431 1,599.29 3,247 1,283 Netherlands 16,627 952.78 — 1,651 Canada 12,906 339.82 2,518 214 Austria 11,679 1,311.86 2,507 186 Portugal 10,524 1,024.07 75 266 South Korea 10,156 196.14 6,325 177 Brazil 9,216 43.61 127 365
  • 13. Israel 7,589 826.69 427 42 Sweden 6,558 634.64 205 391 Australia 5,550 216.24 636 30 Norway 5,548 1,033.61 — 62 Russia 4,731 32.24 333 43 Ireland 4,273 868.23 10 120 Czechia 4,194 392.18 74 56 Denmark 4,077 700.18 1,283 1 Chile 3,737 195.58 427 22 Poland 3,627 94.5 116 79 Romania 3,613 186.19 329 141
  • 14. Malaysia 3,483 106.39 915 57 Ecuador 3,465 198.49 65 172 Philippines 3,094 28.52 57 144 India 3,072 2.26 213 75 Japan 2,935 23.3 514 69 Luxembourg 2,612 4,254.81 80 31 Saudi Arabia 2,179 63.68 420 29 Indonesia 2,092 7.84 150 191 Thailand 2,067 31.09 612 20 Finland 1,875 339.21 — 25 Mexico 1,688 13.34 634 60
  • 15. Panama 1,673 396.56 13 41 Serbia 1,624 233.21 54 44 Greece 1,613 150.4 53 67 Peru 1,595 49.64 537 61 South Africa 1,505 25.61 31 5 United Arab Emirates 1,505 152.17 125 10 Dominican Republic 1,488 143.65 16 68 Iceland 1,364 3,744.58 336 4 Argentina 1,353 30.11 248 42 Colombia 1,267 25.65 55 25 Algeria 1,251 29.09 90 130
  • 16. Singapore 1,189 208.46 297 6 Croatia 1,126 276.23 119 12 Ukraine 1,096 26.17 23 28 Qatar 1,075 391.3 93 3 Estonia 1,018 766.36 59 13 Egypt 985 9.83 216 66 Slovenia 934 446.02 10 20 Iraq 878 22.44 259 56 Hong Kong 862 114.92 173 4 Morocco 858 23.93 62 50 New Zealand 824 165.63 127 1
  • 17. Lithuania 771 276 7 9 Armenia 770 260.36 43 7 Moldova 752 280.42 29 12 Bahrain 688 445.8 399 4 Hungary 678 69.38 58 32 Bosnia and Herzegovina 617 186.91 28 19 Kazakhstan 525 28.11 36 5 Azerbaijan 521 51.75 32 5 Lebanon 520 76.19 50 17 Cameroon 509 19.17 17 8 Latvia 509 266.94 1 1
  • 18. Bulgaria 498 71.14 34 14 Tunisia 495 42.23 5 18 North Macedonia 483 232.53 20 17 Andorra 466 6,009.57 21 17 Slovakia 450 82.47 7 1 Belarus 440 46.74 41 5 Kuwait 417 94.34 82 0 Costa Rica 416 82.25 11 2 Cyprus 386 440.69 18 10 Uruguay 386 109.7 86 4 Taiwan 355 15.04 50 5
  • 19. TREATMENT AND PREVENTION:  At present, there is no single specific antiviral therapy for CoV and the main treatments are supportive.  Recombinant IFN with ribavirin only has limited effects against CoVs infection.  After SARS and MERS epidemics, great efforts have been devoted to development of new antivirals targeting CoVs proteases, polymerases, MTases, and entry proteins, however, none of them has been shown to be efficacious in clinical trials.  Plasma and antibodies obtained from the convalescent patients have been proposed for use in treatment.  Since there is no effective therapy or vaccine, the best measures now are to control the source of infection, early diagnosis, reporting, isolation, supportive treatments, and timely publishing epidemic information to avoid unnecessary panic. For individuals, good personal hygiene, fitted mask, ventilation, and avoiding crowded places will help to prevent CoVs infection.