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The AOP framework and AOP-Wiki

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An AOP is a conceptual construct that portrays the causal linkage between a molecular initiating event (MIE) via a series of Key Events (KE) to an adverse outcome (AO).

The scientific community can share, develop and discuss their AOP in one central location, the publicly accessible AOP Wiki platform https://aopwiki.org, all knowledge disseminated there is open access.

The AOP elements (MIE, KE, AO) are not necessarily unique to a single AOP, value is added to existing knowledge by facilitating the re-use of MIE, KE and AO information in multiple AOPs.

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The AOP modelling COVID-19 outcomes

The AOP framework originates from regulatory toxicology, but molecular initiating events can be triggered by much more than chemicals. In the CIAO project, we consider the SARS-CoV-2 virus as the stressor and we model many COVID-19 outcomes.

AOP379 - Binding of SARS-CoV-2 to ACE2 leading to thrombosis

AOP392 - Decreased fibrinolysis leading to hyperinflammation

AOP412 - Endothelial cell dysfunction leading to thromboinflammation

AOP430 - Binding of SARS-CoV-2 to ACE2 leading to infection proliferation

AOP468 - Binding of SARS-CoV-2 to ACE2 leading to hyperinflammation (via cell death)

AOP320 - Binding of SARS-CoV-2 to ACE2 leading to acute respiratory distress associated mortality

AOP173 - Substance interaction with the lung resident cell membrane components leading to lung fibrosis

AOP319 - Binding to ACE2 leading to lung fibrosis

AOP302 - Lung surfactant function inhibition leading to decreased lung function

AOP374 - Binding of SARS-CoV-2 to ACE2 receptors expressed on brain cells leads to neuroinflammation resulting in encephalitis

AOP394 - Binding of SARS-CoV-2 to ACE2 in olfactory neuroepithelium leading to impaired olfactory function (short-term anosmia)

AOP395 - Binding of SARS-CoV-2 to ACE2 on pericytes leading to intravascular coagulation resulting in stroke

AOP422 - Binding of SARS-CoV-2 to ACE2 in enterocytes leading to disruption of intestinal barrier

AOP428 - ACE2 dysregulation leading to alteration of gut microbiota

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The CIAO project is supported by the Society for the Advancement of Adverse Outcome Pathways (SAAOP), following its mission to promote and advance scientific research that fosters the development and use of AOPs. The AOP Framework is managed by the Organisation for Economic Co-operation and Development (OECD), but the CIAO project is an independent undertaking, making use of the OECD standards.

 

Useful resources:

(*) The course was designed and developed by etioLogic, LLC for the Human Toxicology Project Consortium and is now hosted on the "Animal-Free Safety Assessment (AFSA) Collaboration" website (AFSAcollaboration.org) and is freely available to any and every one. The course can be downloaded as zip files or run directly online by clicking on the link above.

Infection,
Inflammation
& thrombosis

Pulmonary outcomes

Neurologicaloutcomes

Intestinal outcomes

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