This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
Point of Contact
- Shihori Tanabe
|Author status||OECD status||OECD project||SAAOP status|
|Under development: Not open for comment. Do not cite||Under Development||1.96||Included in OECD Work Plan|
This AOP was last modified on June 16, 2022 21:48
|Coagulation||March 25, 2021 20:17|
|Thrombosis and Disseminated Intravascular Coagulation||April 14, 2021 21:52|
|Increased SARS-CoV-2 production||June 14, 2022 08:49|
|SARS-CoV-2 cell entry||July 21, 2022 11:14|
|Diminished protective oxidative stress response||July 03, 2022 22:14|
|Binding to ACE2||May 17, 2022 10:20|
|Interferon-I antiviral response, antagonized by SARS-CoV-2||June 14, 2022 10:29|
|Binding to ACE2 leads to SARS-CoV-2 cell entry||July 21, 2022 07:03|
|SARS-CoV-2 cell entry leads to IFN-I response, antagonized||May 31, 2022 18:07|
|IFN-I response, antagonized leads to SARS-CoV-2 production||October 24, 2021 17:11|
|SARS-CoV-2 production leads to Diminished Protective Response to ROS||April 20, 2021 03:48|
|Diminished Protective Response to ROS leads to Coagulation||April 20, 2021 03:49|
|Coagulation leads to Diminished Protective Response to ROS||April 20, 2021 03:50|
|Coagulation leads to Thrombosis and DIC||March 26, 2021 01:14|
|Stressor:624 SARS-CoV-2||April 20, 2021 03:40|
Coronavirus disease-19 (COVID-19) is circulating all over the world. To understand and find a way of the COVID-19 treatment, the signaling pathway and therapeutic mechanism of COVID-19 should be investigated. The pathogenesis of COVID-19 includes molecular networks such as the binding of the membrane proteins, signaling pathways, and RNA replication. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a new type of coronavirus causing COVID-19, infects the cells via the binding of the membrane proteins of human cells and is internalized by the cells. The viral genome is replicated by RNA-dependent RNA polymerase (RdRp), followed by the packaging and releasing of the viral particles. These steps can be the main targets for the therapeutics of COVID-19. The AOP379 "Increased susceptibility to viral entry and coronavirus production leading to thrombosis and disseminated intravascular coagulation" consists of the molecular initiating events (MIE) as "Increased susceptibility to viral entry" (KE1738) and "Increased coronavirus production" (KE1847), key events (KEs) as "Oxidative stress response" (KE1869) and "Coagulation" (KE1845), and adverse outcome (AO) as "Thrombosis and Disseminated Intravascular Coagulation" (KE1846).
AOP Development Strategy
Summary of the AOP
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
|Type||Event ID||Title||Short name|
|MIE||1739||Binding to ACE2||Binding to ACE2|
|MIE||1738||SARS-CoV-2 cell entry||SARS-CoV-2 cell entry|
|MIE||1847||Increased SARS-CoV-2 production||SARS-CoV-2 production|
|KE||1901||Interferon-I antiviral response, antagonized by SARS-CoV-2||IFN-I response, antagonized|
|KE||1869||Diminished protective oxidative stress response||Diminished Protective Response to ROS|
|AO||1846||Thrombosis and Disseminated Intravascular Coagulation||Thrombosis and DIC|
Relationships Between Two Key Events (Including MIEs and AOs)
|Binding to ACE2 leads to SARS-CoV-2 cell entry||adjacent||High||Moderate|
|SARS-CoV-2 cell entry leads to IFN-I response, antagonized||adjacent||Moderate||Moderate|
|IFN-I response, antagonized leads to SARS-CoV-2 production||adjacent||Moderate||Moderate|
|SARS-CoV-2 production leads to Diminished Protective Response to ROS||adjacent||Moderate||Not Specified|
|Diminished Protective Response to ROS leads to Coagulation||adjacent||Moderate||Not Specified|
|Coagulation leads to Diminished Protective Response to ROS||adjacent||Moderate||Not Specified|
|Coagulation leads to Thrombosis and DIC||adjacent||High|
Life Stage Applicability
|All life stages||Moderate|
|Homo sapiens||Homo sapiens||High||NCBI|
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Known Modulating Factors
Considerations for Potential Applications of the AOP (optional)
Blanco Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, et al. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell. 181;(5):1036-1045.
Chen B, Tian EK, He B, Tian L, Han R, Wang S, et al. Overview of lethal human Coronaviruses. Signal Transduction and Targeted Therapy, 2020;5(1):89.
Cui J, Li F, Shi ZL. Origin and evolution of pathogenic Coronaviruses. Nature Reviews Microbiology. 2019;17(3):181-192.
Florindo HF, Kleiner R, Vaskovich-Koubi D, Acúrcio RC, Carreira B, Yeini,E, et al. Immune-mediated approaches against COVID-19. Nature Nanotechnology. 2020:15(8):630-45.
Kowalewski J, Ray A. Predicting novel drugs for SARS-CoV-2 using machine learning from a & g 10 million chemical space. Heliyon. 2020;6(8).
Pizzorno A, Padey B, Julien T, Trouillet-Assant S, Traversier A, Errazuriz-Cerda E, et al. Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia. Cell Reports Medicine. 2020:1(4).
Riva L, Yuan S, Yin X, Martin-Sancho L, Matsunaga N, Pache L, et al. Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing. Nature. 2020.
Tanabe S (2020a). Cellular Internalization and RNA Regulation of RNA virus. Adv Clin Med Res. 2020;1(1):1-3. https://www.genesispub.org/cellular-internalization-and-rna-regulation-of-rna-virus
Tanabe S (2020b). The Therapeutic Mechanism of COVID-19. J Clin Med Res. 2020;2(5):1-3. DOI: https://doi.org/10.37191/Mapsci-2582-4333-2(5)-048