
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 379
Title
Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation
Short name
Graphical Representation
Point of Contact
Contributors
- Shihori Tanabe
Status
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 Do not cite | Under Development | 1.96 | Included in OECD Work Plan |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 February 05, 2023 19:48
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Coagulation | November 25, 2022 01:36 |
Thrombosis and Disseminated Intravascular Coagulation | November 25, 2022 01:38 |
Increased SARS-CoV-2 production | June 14, 2022 08:49 |
SARS-CoV-2 cell entry | November 25, 2022 01:51 |
Diminished protective oxidative stress response | March 09, 2023 20:49 |
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 | February 07, 2023 23:24 |
SARS-CoV-2 cell entry leads to IFN-I response, antagonized | March 24, 2023 18:04 |
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 | February 05, 2023 20:15 |
Diminished Protective Response to ROS leads to Coagulation | February 05, 2023 20:35 |
Coagulation leads to Diminished Protective Response to ROS | April 20, 2021 03:50 |
Coagulation leads to Thrombosis and DIC | February 05, 2023 20:49 |
Stressor:624 SARS-CoV-2 | April 20, 2021 03:40 |
Abstract
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 "Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation" consists of the molecular initiating event (MIE) as “Binding to ACE2” (KE1739), key events (KEs) as “SARS-CoV-2 cell entry” (KE1738), “Interferon-I antiviral response, antagonized by SARS-CoV-2” (KE1901), "Increased SARS-CoV-2 production" (KE1847), “Diminished protective oxidative stress response" (KE1869) and "Coagulation" (KE1845), and adverse outcome (AO) as "Thrombosis and Disseminated Intravascular Coagulation" (KE1846).
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 1739 | Binding to ACE2 | Binding to ACE2 |
KE | 1738 | SARS-CoV-2 cell entry | SARS-CoV-2 cell entry |
KE | 1901 | Interferon-I antiviral response, antagonized by SARS-CoV-2 | IFN-I response, antagonized |
KE | 1847 | Increased SARS-CoV-2 production | SARS-CoV-2 production |
KE | 1869 | Diminished protective oxidative stress response | Diminished Protective Response to ROS |
KE | 1845 | Coagulation | Coagulation |
AO | 1846 | Thrombosis and Disseminated Intravascular Coagulation | Thrombosis and DIC |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
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 |
Network View
Prototypical Stressors
Life Stage Applicability
Life stage | Evidence |
---|---|
All life stages | Moderate |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
Homo sapiens | Homo sapiens | High | NCBI |
Sex Applicability
Sex | Evidence |
---|---|
Unspecific | High |
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Modulating Factor (MF) | Influence or Outcome | KER(s) involved |
---|---|---|
Quantitative Understanding
Considerations for Potential Applications of the AOP (optional)
References
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