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Aop: 320

AOP Title

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Binding of viral S-glycoprotein to ACE2 receptor leading to acute respiratory distress associated mortality

Short name:

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S glycoprotein, Acute respiratory distress

Graphical Representation

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Click to download graphical representation template

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Authors

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Point of Contact

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Young Jun Kim   (email point of contact)

Contributors

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  • Young Jun Kim

Status

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Author status OECD status OECD project SAAOP status
Open for citation & comment


This AOP was last modified on March 17, 2020 06:05

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Revision dates for related pages

Page Revision Date/Time
Increased, secretion of proinflammatory and profibrotic mediators October 30, 2019 11:28
Enhanced viral entry and gene expression March 01, 2020 10:29
Binding of S protein to ACE receptor March 02, 2020 03:18
Increase, the risk of acute respiratory failure March 10, 2020 02:05
Increase inflammatory immune responses March 10, 2020 02:17
Decreased mortality March 17, 2020 06:04
Binding of S protein to ACE receptor leads to Enhanced viral entry and gene expression March 02, 2020 03:19
Enhanced viral entry and gene expression leads to Increased proinflammatory mediators March 01, 2020 10:31
Increased proinflammatory mediators leads to Increase inflammatory immune responses March 10, 2020 02:18
Increase inflammatory immune responses leads to Increase, the risk of acute respiratory failure March 10, 2020 02:19
Increase, the risk of acute respiratory failure leads to Decreased mortality March 17, 2020 06:05
SARS-CoV March 01, 2020 10:42
COVID-19 March 01, 2020 10:46

Abstract

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Inhalation of substances, including viral particles,  the RNA virus capsid (S) glycoprotein binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition. The AOP report the S glycoprotein of viral capsid in complex with its host cell receptor ACE2 resulted in acute respiratory distress associated mortality by enhanced inflammation in pulmonary tissue.


Background (optional)

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The ACE2 gene encodes the angiotensin-converting enzyme-2, which has been proved to be the receptor for both the SARS-coronavirus (SARS-CoV) and the human respiratory coronavirus. The higher levels of receptor expression achieved by expression of recombinant ACE2 could be relevant for cell–cell fusion. The underlying mechanisms remain to be elucidated and could play a role in the entry of cell-free virus into cells and finally acute respiratory distress associated mortality .


Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
MIE 1739 Binding of S protein to ACE receptor Binding of S protein to ACE receptor
KE 1738 Enhanced viral entry and gene expression Enhanced viral entry and gene expression
KE 1496 Increased, secretion of proinflammatory and profibrotic mediators Increased proinflammatory mediators
KE 1750 Increase inflammatory immune responses Increase inflammatory immune responses
KE 1748 Increase, the risk of acute respiratory failure Increase, the risk of acute respiratory failure
AO 1751 Decreased mortality Decreased mortality

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Binding of S protein to ACE receptor leads to Enhanced viral entry and gene expression adjacent High Low
Enhanced viral entry and gene expression leads to Increased proinflammatory mediators adjacent Low Low
Increased proinflammatory mediators leads to Increase inflammatory immune responses adjacent High Low
Increase inflammatory immune responses leads to Increase, the risk of acute respiratory failure adjacent Moderate Low
Increase, the risk of acute respiratory failure leads to Decreased mortality adjacent Moderate Low

Network View

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Stressors

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Name Evidence Term
SARS-CoV Moderate
COVID-19 Moderate

Life Stage Applicability

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Life stage Evidence
Conception to < Fetal Low

Taxonomic Applicability

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Term Scientific Term Evidence Link
Homo sapiens Homo sapiens Moderate NCBI

Sex Applicability

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Sex Evidence
Mixed High

Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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This AOP not only contributes new tools to study entry of the viral particles into cells and localize its receptor-binding domain of ACE2 but also could serve in the development of novel vaccine immunogens and therapeutics for prevention and treatment of RNA virus.


References

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  1.  Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W, Bao L, Zhang B, Liu G, Wang Z, Chappell M, Liu Y, Zheng D, Leibbrandt A, Wada T, Slutsky AS, Liu D, Qin C, Jiang C, Penninger JM (Aug 2005). "A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury". Nature Medicine11 (8): 875–9. doi:10.1038/nm1267PMID 16007097.
  2. ^ "What are the official names of the disease and the virus that causes it?"Q&A on coronaviruses. World Health Organization. Retrieved 22 February 2020.
  3. ^ Zhou P, Yang X (2020-02-03). "A Pneumonia Outbreak Associated With a New Coronavirus of Probable Bat Origin". Naturedoi:10.1038/s41586-020-2012-7PMID 32015507.
  4. ^ Xintian, Xu; Chen, Ping (2020). "Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission". Science China Life Sciencesdoi:10.1007/s11427-020-1637-5PMID 32009228.
  5. ^ Lewis, Ricki. "COVID-19 Vaccine Will Close in on the Spikes"DNA Science Blog. Public Library of Science. Retrieved 22 February 2020.
  6. ^ Walls, Alexandra; et al. (2020). "Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein"bioRxiv. bioRxiv. doi:10.1101/2020.02.19.956581. Retrieved 22 February 2020.
  7. He L,et al (2006).Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS.J Pathol. 2006 Nov;210(3):288-97.​