Since the starting of the Coronavirus Pandemic around the world, Everyone wants to know about coronavirus nCoV-19. This ppt will cover different strains of Coronaviruses that have been discovered since 1966 - Their Epidemiology and Pathophysiology. Discussion about the pandemics and epidemics that happened before the novel coronavirus pandemic. While the main focus of the class will be on : (1) The causative strains of coronaviruses that were involved to cause those pandemics/ epidemics. (2) Genetics recombination among them to evolve more pathogenic strains.

1. Gaurav Aggarwal
MSc Life Sciences( Bioinformatics)
Central University of Punjab, India
Coronavirus and the five strains
On Classtree.in
Special thanks
To
Team of classtree

2. Epidemiology, Genetic
Recombination, and
Pathogenesis of Coronaviruses
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis
of Coronaviruses. Trends in Microbiology, 24(6), 490–502

3. Authors
Shuo Su,1,*, Gary Wong,2,3,4, Weifeng Shi,5, Jun Liu,4,6, Alexander C.K.
Lai,7 Jiyong Zhou,1, Wenjun Liu,3,4 Yuhai Bi,2,3,4,* ,
George F. Gao2,3,4,6,8,9,*
1. Engineering Laboratory of Animal Immunity of Jiangsu Province, Institute of
immunology and College of Veterinary Medicine, Nanjing Agricultural University,
Nanjing, China.
2. Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's
Hospital, Shenzhen, China
3. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of
Microbiology, Chinese Academy of Sciences, Beijing, China
4. CAS Center for Influenza Research and Early-Warning (CASCIRE), Chinese
Academy of Sciences, Beijing, China
5. Institute of Pathogen Biology, Taishan Medical College, Taian, China
6. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease
Control and Prevention (China CDC), Beijing, China
7. Kentucky State University, Frankfort, Kentucky, USA
8. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease,
Zhejiang University, Hangzhou, China
9. University of Chinese Academy of Sciences Medical School, Chinese Academy of
Sciences, Beijing, China
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

4. Objective
In this review researchers aims to compare and
contrast the different HCoVs with regard to
epidemiology and pathogenesis, in addition to
the virus evolution and recombination events
which have, on occasion, resulted in outbreaks
amongst humans as ongoing in world in 2020.
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis
of Coronaviruses. Trends in Microbiology, 24(6), 490–502

5. Introduction
Virus strain: Noval Coronavirus (nCoV)
Family: Coronaviridae
Capsulation of virus: Encapsulated
Genome: ss (+) RNA
Genome size: 26-32 kb
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

6. Contd...
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502.
http://ictvonline. org/proposals/2008.085-122 V.v4.Coronaviridae.pdf
Coronavirus
Alpha-CoV
Beta-CoV
Gamma-CoV
Delta-CoV
C
B
A
Genera Lineages
D

7. Contd...
• In humans, CoV infections primarily involve the
upper respiratory tract and the gastrointestinal
tract, and vary from mild, self-limiting disease,
such as the common cold, to more severe
manifestations, such as bronchitis and
pneumonia with renal involvement.
• The first human coronavirus (HCoV) was isolated
during 1965 from the nasal discharge of patients
with the common cold and termed B814.
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

8. Contd...
• Six different CoV strains are known to infect
humans-
HCoV229E (229E)
HCoV-OC43 (OC43)
severe acute respiratory syndrome coronavirus
(SARS-CoV)
HCoV-NL63 (NL63)
HCoV-HKU1 (HKU1)
Middle East respiratory syndrome coronavirus
(MERS-CoV)
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502

9. Human Coronavirus 229E
(alphacoronavirus)
• Strain 229E was discovered during 1966, when researchers were
characterizing five novel agents that were isolated from the
respiratory tract of humans who had contracted the common cold.
• 229E was adapted to grow in WI-38 lung fibroblast cell lines, and
was later shown to be morphologically identical to IBV and MHV .
• Symptoms of 229E infection include general malaise, headache,
nasal discharge, sneezing, and a sore throat .
• A small portion of patients (10–20%) will also exhibit fever and
cough.
• The incubation time is approximately 2–5 days, followed by illness
lasting between 2 and 18 days, and clinically indistinguishable from
respiratory tract infections caused by other pathogens, such as
rhinovirus and influenza A.
• 229E is distributed globally.
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502

10. Human Coronavirus OC43
(betacoronavirus, lineage A)
• Human Coronavirus OC43 (betacoronavirus, lineage A)
Strain OC43 was discovered, during 1967, in the
nasopharyngeal wash of a patient with the common
cold, and is adapted to grow in organ cultures
containing suckling mouse brains.
• Similar to 229E, OC43 is morphologically
indistinguishable from IBV and MHV and patients
infected with OC43 present the same clinical symptoms
as that of 229E.
• However, there is no serological cross-reactivity
between 229E and OC43 .
• OC43 is also distributed globally
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502

11. SARS-CoV (betacoronavirus, lineage B)
• Patients infected with SARS-CoV initially present with fever, myalgia,
headache, malaise, and chills, followed by a nonproductive cough,
dyspnea, and respiratory distress generally 5 to 7 days later, which
may result in death .
• Other notable features in some cases include infection of the
gastrointestinal tract, liver, kidney, and brain.
• Diffuse alveolar damage, epithelial cell proliferation, and an
increase in macrophages is seen in SARS-CoV infection of the lung.
• Lymphopenia, hemophagocytosis in the lung, in addition to white-
pulp atrophy of the spleen observed in SARS patients, are similar to
fatal H5N1 influenza virus infections.
• Diarrhea is observed in approximately 30–40% of SARS infections
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502

12. Contd...
• An outbreak of disease caused by SARS-CoV,
originating from Guangdong Province in southern
China during November 2002, eventually spread to
other countries in Asia, in addition to North America
and Europe (37 countries/regions in total) over 9
months.
• An eventual 8273 cases were reported, with 775
deaths for a case fatality rate (CFR) of 9%, and the
majority of cases and deaths occurred in mainland
China and in Hong Kong .
• The elderly were more susceptible to SARS disease,
with a mortality rate of over 50%
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502

13. Human Coronavirus NL63
(alphacoronavirus)
• NL63 is primarily associated with young children, the
elderly, and immunocompromised patients with respiratory
illnesses.
• NL63 was a novel HCoV isolated from a 7-month-old child
with coryza, conjunctivitis, fever, and bronchiolitis in the
Netherlands during late 2004, and an independent
investigation described the isolation of virtually the same
virus from a nasal sample collected from an 8-month-old
boy suffering from pneumonia in the Netherlands.
• NL63 was also detected in New Haven, USA, during 2005
amongst 79 of 895 children, and was initially called HCoV-
NH (NH), but genetic and phylogenetic analyses showed
that NH and HKU1 likely are the same species .
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502

14. Contd...
• Infections with NL63 typically result in mild
respiratory disease similar to the common cold,
characterized by cough, rhinorrhea, tachypnea,
fever, and hypoxia, and resolve on their own .
• Obstructive laryngitis, also known as croup, is
frequently observed with NL63 infections.
• A study estimated that NL63 accounts for an
estimated 4.7% of common respiratory diseases.
• NL63 is distributed globally
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502

15. Human Coronavirus HKU1
(betacoronavirus, lineage A)
• Human Coronavirus HKU1 (betacoronavirus, lineage A) HKU1 was first
discovered during January 2005 in a 71-year-old patient from Hong Kong
who had been hospitalized with pneumonia and bronchiolitis.
• The symptoms of HKU1 respiratory tract infections are not able to be
separated from those caused by other respiratory viruses. Most patients
present with fever, running nose, and cough for infections in the upper
respiratory tract, whereas a fever, productive cough, and dyspnea are the
common symptoms presenting for infections in the lower respiratory tract
• Most HKU1 infections are self-limiting, with only two deaths reported in
patients with pneumonia due to HKU1.
• Although HKU1 is clinically relatively mild in children, HKU1 infection is
associated with a high incidence of seizures, and was found in a patient
with meningitis.
• HKU1 cases outside Asia were detected in New Haven, USA, in 2 out of
851 children, and also in Australia, France, and Brazil, indicating a global
distribution for the virus.
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

16. MERS-CoV (betacoronavirus, lineage C)
• MERS-CoV was first isolated from the lungs of a 60-year-old patient
who had died from a severe respiratory illness in Jeddah, Saudi
Arabia, 2012 .
• Clinical manifestations of MERS-CoV infection range from
asymptomatic to severe pneumonia with acute respiratory distress,
septic shock, and renal failure resulting in death .
• A typical disease course begins with fever, cough, chills, sore throat,
myalgia, and arthralgia, followed by dyspnea and rapid progression
to pneumonia.
• Approximately one-third of patients present with gastrointestinal
symptoms, such as diarrhea and vomiting. Acute renal impairment
was the most striking feature of disease caused by MERS-CoV,
which is thus far unique for human CoV infections.
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502

17. Contd...
• 75% of patients with MERS disease also had at least one
other co-morbidity, and patients who died were more likely
to have a pre-existing/underlying condition. Countries
around the Arabian Peninsula are known to be endemic for
MERS-CoV, and Saudi Arabia has reported the most cases,
but since its discovery in 2012, cases have been
occasionally exported to other countries through travel,
sometimes causing clusters of secondary outbreaks .
• As of December 31, 2015, a total of 1621 laboratory-
confirmed infections have been reported, with 584 deaths
(CFR = 36.0%) over 26 countries , making MERS-CoV one of
the most dangerous viruses known to humans.
• CFR = Case Fatality rate = Deaths due to disease
Cases Reported
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502

18. Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502
Fig1: Global Distribution of Human Coronaviruses

19. Ecology of Human Coronaviruses
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502

20. Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

21. Phylogeny, Evolution and Genetic
Recombination in Human Coronaviruses
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502

22. Phylogenetic tree based on whole
genome sequencing
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

23. Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

24. Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

25. Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

26. Genetic Recombination in Human
Coronaviruses
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

27. Contd…
Strains Nucleotide mutation rate (NMR)
Substitutions/site/year
OC43 (S-gene) 6.41058*10-4
229E (S-gene) 3*10-4
SARS-CoV
(whole genome)
0.80-2.38*10-3
MERS-CoV 1.12*10-3
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

28. SARS-CoV
• TOR2 strain
 Possible recombinant history with lineages of alpha
and gamma CoV.
Many specific breakpoints and a large number of
smaller recombinant regions in the RDRP(HSP2 gene).
Loc: 13392-13610 , 15259-15324 , 15974-16108
(based on SARS-CoV TOR2).
Loc: NSP9-NSP10: 12613-13344 , NSP14 : 18117-18980
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

29. Contd…
• CV7 strain
Seven putative Recombination locations found between
SARS-CoV and other CoVs (PEDV, TGEV, BCV, 229E, MHV, IBV)
Suggests SARS-CoV emerged via serial horizontal
transmission, genetic recombination
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

30. Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

31. Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

32. Why Coronaviruses are having high
frequency of Recombinations?
• Large RNA genome in Coronavirus allows for
extra plasticity in genome modification by
mutations and recombinations thereby
increasing probability for intraspecies
variability, interspecies host jumps and novel
coronavirus (nCoV) to emerge under the right
conditions.
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

33. Process of recombination in
Coronavirus
• During Replication:-
Generation of Set of Sub-genomic RNAs.
Increasing Homologous Recombination Rate
among closely related genes from different
lineages of coronavirus by Template switching.
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and
Pathogenesis of Coronaviruses. Trends in Microbiology, 24(6), 490–502

34. Concluding Remarks
• The result from a high frequency of recombination
events in CoVs is the generation of novel viruses with a
high genetic diversity, with unpredictable changes in
virulence during human infections. With multiple
species of CoVs circulating in the wild amongst
different animal species that may constantly interact
with one another, it is likely not a matter of if, but
when, the next recombinant CoV will emerge and
cause another outbreak in the human population.
• Furthermore, lessons from the SARS-CoV and MERS-
CoV outbreaks must be urgently learned in advance to
effectively prepare for the next CoV outbreak.
Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502

35. References
1. Su, S., Wong, G., Shi, W., Liu, J., Lai, A. C. K., Zhou, J., … Gao, G. F. (2016).
Epidemiology, Genetic Recombination, and Pathogenesis of
Coronaviruses. Trends in Microbiology, 24(6), 490–502. (doi:
10.1016/j.tim.2016.03.003)
2. PDF of above reference was downloaded from Pubmed-Central-
NCBI(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125511/pdf/mai
n.pdf) “Elsevier hereby grants permission to make all its COVID-19-
related research that is available on the COVID-19 resource centre -
including this research content - immediately available in PubMed
Central and other publicly funded repositories, such as the WHO COVID
database with rights for unrestricted research re-use and analyses in
any form or by any means with acknowledgement of the original
source. These permissions are granted for free by Elsevier for as long as
the COVID-19 resource centre remains active”.
3. Animated diagrams were made using website (https://miro.com/) on
slide number 20, 22, 23, 24, 25, 30,31 respectively .

36. Feel free to connect
gaurav989989@yahoo.com
https://sites.google.com/view/gaurav-aggarwal-nanogram
https://www.linkedin.com/in/gaurav-aggarwal-8397b7141/

37. FOG INDEX of tutorial 08-06-2020 file
0
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7 8 9 10 11 12 13 14 15 16 17 28 29 32 33 34 35
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Slide number of tutorial 08-06-2020
The fog index is commonly used to confirm that text can be read easily by the intended
audience. Fog index identifier is an algorithm based tool that estimates complexity of
sentences. (https://www.webfx.com/tools/read-able/check.php)
FOG Score = 0.4 x ( (words/sentences) + 100 x (complexWords/words) )