
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 430
Title
Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation
Short name
Graphical Representation
Point of Contact
Contributors
- Sally Mayasich
- Laure-Alix Clerbaux
- Maria Joao Amorim
- Arthur Author
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 Do not cite | Under Development | 1.96 | Included in OECD Work Plan |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 July 16, 2022 18:37
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Binding to ACE2 | May 17, 2022 10:20 |
SARS-CoV-2 cell entry | June 18, 2022 11:10 |
Interferon-I antiviral response, antagonized by SARS-CoV-2 | June 14, 2022 10:29 |
Increased SARS-CoV-2 production | June 14, 2022 08:49 |
Viral infection and host-to-host transmission, proliferated | October 24, 2021 15:55 |
Binding to ACE2 leads to SARS-CoV-2 cell entry | October 24, 2022 07:43 |
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 Viral infection, proliferated | October 24, 2021 17:12 |
SARS-CoV | March 01, 2020 10:42 |
Sars-CoV-2 | February 23, 2021 04:50 |
HCoV-NL63 | February 07, 2021 07:01 |
Abstract
SARS and SARS-CoV-2 coronoviruses enter the cell through interaction with the ACE2 receptor. The first event upon cell entry after uncoating is the primary translation of the ORF1a and ORF1b genomic RNA to produce non-structural proteins (nsps). The nsps structural proteins, and accessory proteins, are encoded by 10 ORFs in the SARS-CoV-2 RNA genome. They may have multiple functions during viral replication as well as in evasion of the host innate immune response, thus augmenting viral replication and spread. The early innate immune system evasion proteins produced in the sub-genomic translation after viral genome replication and transcription within the infected cell suppress the Interferon-I antiviral response to increase viral load. Beyond potentially contributing to the severity of clinical symptoms and adverse disease outcome in individuals, increase in viral load can lead to proliferation from person-to-person and across species, also increasing the likelihood of mutations that result in more infective or virulant strains.
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 |
AO | 1939 | Viral infection and host-to-host transmission, proliferated | Viral infection, proliferated |
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 | High | Not Specified |
IFN-I response, antagonized leads to SARS-CoV-2 production | adjacent | High | Not Specified |
SARS-CoV-2 production leads to Viral infection, proliferated | adjacent | High | Not Specified |
Network View
Prototypical Stressors
Name |
---|
SARS-CoV |
Sars-CoV-2 |
HCoV-NL63 |
Life Stage Applicability
Life stage | Evidence |
---|---|
All life stages | High |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
mink | Mustela lutreola | High | NCBI |
ferret | Mustela putorius furo | High | NCBI |
cat | Felis catus | High | NCBI |
dog | Canis lupus familiaris | High | NCBI |
Syrian golden hamster | Mesocricetus auratus | High | NCBI |
rhesus macaque | Macaca mulatta | High | NCBI |
lowland gorilla | Gorilla gorilla gorilla | High | NCBI |
crab eating macaque | Macaca fascicularis | High | NCBI |
African green monkeys | Chlorocebus aethiops | High | NCBI |
humans | Homo sapiens | High | NCBI |
Hippopotamus amphibius | Hippopotamus amphibius | High | NCBI |
bank vole | Myodes glareolus | High | NCBI |
Lynx canadensis | Lynx canadensis | High | NCBI |
Puma concolor | Puma concolor | High | NCBI |
Panthera tigris jacksoni | Panthera tigris jacksoni | High | NCBI |
Panthera uncia | Uncia uncia | High | NCBI |
Prionailurus viverrinus | Prionailurus viverrinus | High | NCBI |
Crocuta crocuta | Crocuta crocuta | High | NCBI |
Arctictis binturong | Arctictis binturong | High | NCBI |
Odocoileus virginianus | Odocoileus virginianus | High | NCBI |
American mink | Neovison vison | High | NCBI |
Nasua nasua | Nasua nasua | High | NCBI |
Panthera leo | Panthera leo | High | NCBI |
Sus scrofa | Sus scrofa | High | NCBI |
European rabbit | Oryctolagus cuniculus | High | NCBI |
Castor fiber | Castor fiber | High | NCBI |
Aonyx cinereus | Aonyx cinerea | High | NCBI |
Vulpes vulpes | Vulpes vulpes | High | NCBI |
Nyctereutes procyonoides | Nyctereutes procyonoides | High | NCBI |
Tupaia belangeri | Tupaia belangeri | High | NCBI |
Bos taurus | Bos taurus | High | NCBI |
Odocoileus hemionus | Odocoileus hemionus | High | NCBI |
Peromyscus maniculatus bairdii | Peromyscus maniculatus bairdii | High | NCBI |
Cynopterus brachyotis | Cynopterus brachyotis | High | NCBI |
common marmoset | Callithrix jacchus | High | NCBI |
baboon | Papio anubis | High | NCBI |
Sex Applicability
Sex | Evidence |
---|---|
Unspecific | Not Specified |