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 - Increased susceptibility to viral entry and coronavirus production leading to thrombosis and disseminated intravascular coagulation

AOP392 - Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation

AOP412 - SARS-COV-2 infection leading to thromboinflammation

AOP430 - SARS-CoV-2 IFN-I antiviral antagonism leading to infection proliferation

AOP320 - Binding of S-protein to ACE2 receptor leading to acute respiratory distress associated mortality

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

AOP377 - TLR9 activation leading to ARDS and Multi Organ Dysfunction

AOP319 - Inhibition of Angiotensin-converting enzyme 2 leading to lung fibrosis

AOP302 - Lung surfactant function inhibition leading to decreased lung function

AOP382 - Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis

AOP374 - Binding of S-protein to ACE2 receptors expressed on brain cells leads to neuroinflammation resulting in encephalitis

AOP394 - SARS-CoV-2 infection leading to impaired olfactory function (anosmia)

AOP395 - Binding of S-protein to ACE2 receptors expressed on pericytes leads to intravascular coagulation resulting in stroke

AOP422 - Binding of SARS-CoV-2 to ACE2 in enterocytes leading to gastrointestinal disorders

AOP428 - ACE2 dysregulation leads to gastrointestinal disorders

AOP427 - Downregulation of ACE2 causes multi-factorial heart injury and heart failure

AOP383 - Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis

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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.