This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Increased susceptibility to viral entry and coronavirus production leading to thrombosis and disseminated intravascular coagulation
Point of Contact
- Shihori Tanabe
- Arthur Author
|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 Do not cite||Under Development||1.96||Included in OECD Work Plan|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 May 08, 2022 11:33
|Coagulation||March 25, 2021 20:17|
|Thrombosis and Disseminated Intravascular Coagulation||April 14, 2021 21:52|
|Increased coronavirus production||April 20, 2021 00:54|
|Increased susceptibility to viral entry||April 27, 2021 19:46|
|Depletion of protective oxidative stress response||January 05, 2022 00:04|
|Increased susceptibility to viral entry leads to Increased SARS-CoV-2 production||March 30, 2021 22:06|
|Increased SARS-CoV-2 production leads to Depleted Protective Response to ROS||April 20, 2021 03:48|
|Depleted Protective Response to ROS leads to Coagulation||April 20, 2021 03:49|
|Coagulation leads to Depleted 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).
Summary of the AOP
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
|Sequence||Type||Event ID||Title||Short name|
|1||MIE||1738||Increased susceptibility to viral entry||Increased susceptibility to viral entry|
|2||MIE||1847||Increased coronavirus production||Increased SARS-CoV-2 production|
|3||KE||1869||Depletion of protective oxidative stress response||Depleted Protective Response to ROS|
|5||AO||1846||Thrombosis and Disseminated Intravascular Coagulation||Thrombosis and DIC|
Relationships Between Two Key Events (Including MIEs and AOs)
|Increased susceptibility to viral entry leads to Increased SARS-CoV-2 production||adjacent||High||Moderate|
|Increased SARS-CoV-2 production leads to Depleted Protective Response to ROS||adjacent||Moderate||Not Specified|
|Depleted Protective Response to ROS leads to Coagulation||adjacent||Moderate||Not Specified|
|Coagulation leads to Depleted 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
Considerations for Potential Applications of the AOP (optional)
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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