severe acute respiratory syndrome (sars): breath-taking … · sars-cov receptor is the...

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Severe acute respiratory syndrome (SARS): breath-taking disease and research progress WHO’s Carlo Urbani died from SARS SARS on the march SARS dancers SARS vogue It took 5 weeks to nail the agent, a virus from the family Coronaviridae SARS was first described in 2002 in Guangdong province, China, where patients developed flu-like illness often followed by acute atypical pneumonia, respiratory failure, and death

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Page 1: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

Severe acute respiratory syndrome (SARS): breath-taking disease and research progress

WHO’s Carlo Urbani died from SARS

SARS on the march SARS dancers SARS vogue

It took 5 weeks to nail the agent, a virus from the family Coronaviridae

SARS was first described in 2002 in Guangdong province, China, where patients developed flu-like illness often followed by acute atypical pneumonia, respiratory failure, and death

Page 2: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

Poetically enough, Chinese doctors described the pulmonary infiltrates that appear on X-rays of SARS patients as the ‘blossoming flower’ lesions…

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Page 3: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

From index case, around

the globe

Page 4: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

Sites of viral entry in the respiratory tract

Page 5: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

An aftermath of the SARS outbreak: 8,000 reported cases, 774 reported deaths

In the end, it wasn’t science that brought SARS under control

Centuries-old measures, such as strict isolation of patients, eventually cornered the virus

Where it came from?

Will it come back?

Page 6: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

Vietnam

Canada

Containment of SARS in Vietnam and Toronto

Page 7: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

Structure of the coronavirus particle

S, spike; M, membrane; E, envelope (ion channel, virus budding and release)

glycoproteins; S mediates both attachment

and membrane fusion N, nucleocapsid protein

(also acts as interferon antagonist)

corona = crown

~30,000 nt, positive-strand RNA, the largest known

RNA genomes

Page 8: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component of the system, which controls blood

pressure. It is also believed to protect lungs during inflammation. Just two amino acid changes in S resulted in efficient binding of human

receptor and cross-species transmission of SARS-CoV.

SARS-CoV uses the same ACE2 receptor as human coronavirus NL-63

Page 9: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

Variation in genome sizes among +RNA viruses

Page 10: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

SCoV genome structure, a simple version

Replication and transcription; proteinases, -1 frameshift

Virion; sg mRNAs

Page 11: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

SARS-CoV genome, a bioinformaticist’s view

RNA synthesis and processing

Page 12: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

Coronavirus life cycle

SARS-CoV is almost invisible to innate immunity (interferon response); N-protein also contributes to its evasion. Because of this, viral clearance is delayed and followed by cytokine storm causing immunopathology and systemic disease.

Page 13: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

Phylogenetic analysis of coronavirus replicase genes

?

Page 14: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

Human and animal SARS-CoVs (S gene)

Dr. Yi Guan

Palm civet Racoon dog

Page 15: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

There are different ways of dealing with palm civets...

Page 16: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

The horseshoe bats as a natural reservoir of SARS-CoV

Phylogenetic tree for RdRps of coronaviruses

Colony of bats. Some bats are considered a delicacy;

Can be found on ‘wet’ markets

Page 17: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

Global risk distribution of an emerging infectious disease event

a, zoonotic pathogens from wildlife, b, zoonotic pathogens from non-wildlife, c, drug-resistant pathogens and d, vector-borne pathogens.

After SARS that invigorated coronovirology, ~100 novel coronaviruses were found in bats, birds (similar viruses were found in wild leopard cats and badgers indicating cross-species transmission), and even beluga whales.

So far, there is no effective treatment for SARS; vaccines tend to be inefficient…

Page 18: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

On February 11, 2013, WHO stated that there had been 11 laboratory-confirmed cases, 5 cases (3 fatal) from Saudi Arabia, 2 cases (both fatal) from Jordan, 2 cases from

Qatar, and 2 from the UK

Enter Novel Coronavirus, or ‘Saudi-SARS’

Page 19: Severe acute respiratory syndrome (SARS): breath-taking … · SARS-CoV receptor is the cell-surface zinc peptidase, angiotensin-converting enzyme 2 (ACE2) that is an important component

Recommended reading

Guan et al. (2003) Isolation and characterization of viruses related to the SARS coronavirus from animals in Southern China. Science 302:276-278.

Perlman and Netland (2009) Coronaviruses post-SARS. Nat. Rev. Microbiol. 7:439-450.