The AOP framework and AOP-Wiki
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.
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 and disseminated intravascular coagulation
AOP392 - Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation
AOP412 - SARS-COV-2 infection leading to thromboinflammation
AOP430 - Binding of SARS-CoV-2 to ACE2 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 disruption of intestinal barrier
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
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.
Find out more about the OECD AOP Framework here
Try this online training course(*) about the AOP Framework
(*) 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.