This AOP is licensed under a Creative Commons Attribution 4.0 International License.

Aop: 430

Title

A descriptive phrase which references both the Molecular Initiating Event and Adverse Outcome.It should take the form “MIE leading to AO”. For example, “Aromatase inhibition leading to reproductive dysfunction” where Aromatase inhibition is the MIE and reproductive dysfunction the AO. In cases where the MIE is unknown or undefined, the earliest known KE in the chain (i.e., furthest upstream) should be used in lieu of the MIE and it should be made clear that the stated event is a KE and not the MIE. More help

Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation

Short name

A name that succinctly summarises the information from the title. This name should not exceed 90 characters. More help

SARS-CoV-2 leads to infection proliferation

Graphical Representation

A graphical representation of the AOP.This graphic should list all KEs in sequence, including the MIE (if known) and AO, and the pair-wise relationships (links or KERs) between those KEs. More help

Click to download graphical representation template Explore AOP in a Third Party Tool

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Authors

The names and affiliations of the individual(s)/organisation(s) that created/developed the AOP. More help

Sally Mayasich, University of Wisconsin-Madison Aquatic Sciences Center at US Environmental Protection Agency, Duluth, MN, USA

Maria Joao Amorim, Instituto Gulbenkian de Ciência, Oeiras, Portugal

Laure-Alix Clerbaux, European Commission-Joint Research Centre (EC-JRC), Ispra, Italy

Alicia Paini, EC-JRC/EsqLab

Nikolaos Parissis, EC-JRC

Kim Young Jun, KIST Europe, Germany

Penny Nymark, Institute of Environmental Medicine, Karolinska Institute, Sweden

Point of Contact

The user responsible for managing the AOP entry in the AOP-KB and controlling write access to the page by defining the contributors as described in the next section. More help

Arthur Author (email point of contact)

Contributors

Users with write access to the AOP page. Entries in this field are controlled by the Point of Contact. More help

Sally Mayasich
Laure-Alix Clerbaux
Maria Joao Amorim
Arthur Author

Status

Provides users with information concerning how actively the AOP page is being developed, what type of use or input the authors feel comfortable with given the current level of development, and whether it is part of the OECD AOP Development Workplan and has been reviewed and/or endorsed. OECD Status - Tracks the level of review/endorsement the AOP has been subjected to. OECD Project Number - Project number is designated and updated by the OECD. SAAOP Status - Status managed and updated by SAAOP curators. More help

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

A concise and informative summation of the AOP under development that can stand-alone from the AOP page. The aim is to capture the highlights of the AOP and its potential scientific and regulatory relevance. More help

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

Used to provide background information for AOP reviewers and users that is considered helpful in understanding the biology underlying the AOP and the motivation for its development.The background should NOT provide an overview of the AOP, its KEs or KERs, which are captured in more detail below. More help

Strategy

Provides a description of the approaches to the identification, screening and quality assessment of the data relevant to identification of the key events and key event relationships included in the AOP or AOP network.This information is important as a basis to support the objective/envisaged application of the AOP by the regulatory community and to facilitate the reuse of its components. Suggested content includes a rationale for and description of the scope and focus of the data search and identification strategy/ies including the nature of preliminary scoping and/or expert input, the overall literature screening strategy and more focused literature surveys to identify additional information (including e.g., key search terms, databases and time period searched, any tools used). More help

Summary of the AOP

This section is for information that describes the overall AOP. The information described in section 1 is entered on the upper portion of an AOP page within the AOP-Wiki. This is where some background information may be provided, the structure of the AOP is described, and the KEs and KERs are listed. More help

Events:

Molecular Initiating Events (MIE)

An MIE is a specialised KE that represents the beginning (point of interaction between a prototypical stressor and the biological system) of an AOP. More help

Key Events (KE)

A measurable event within a specific biological level of organisation. More help

Adverse Outcomes (AO)

An AO is a specialized KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

Type	Event ID	Title	Short name

MIE

1739

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

1939

Viral infection and host-to-host transmission, proliferated

Viral infection, proliferated

Relationships Between Two Key Events (Including MIEs and AOs)

This table summarizes all of the KERs of the AOP and is populated in the AOP-Wiki as KERs are added to the AOP.Each table entry acts as a link to the individual KER description page. More help

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

This network graphic is automatically generated based on the information provided in the MIE(s), KEs, AO(s), KERs and Weight of Evidence (WoE) summary tables. The width of the edges representing the KERs is determined by its WoE confidence level, with thicker lines representing higher degrees of confidence. This network view also shows which KEs are shared with other AOPs. More help

Prototypical Stressors

A structured data field that can be used to identify one or more “prototypical” stressors that act through this AOP. Prototypical stressors are stressors for which responses at multiple key events have been well documented. More help

Name
SARS-CoV
Sars-CoV-2
HCoV-NL63

Life Stage Applicability

The life stage for which the AOP is known to be applicable. More help

Life stage	Evidence
All life stages	High

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) can be selected.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available. More help

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

The sex for which the AOP is known to be applicable. More help

Sex	Evidence
Unspecific	Not Specified

Overall Assessment of the AOP

Addressess the relevant biological domain of applicability (i.e., in terms of taxa, sex, life stage, etc.) and Weight of Evidence (WoE) for the overall AOP as a basis to consider appropriate regulatory application (e.g., priority setting, testing strategies or risk assessment). More help

Domain of Applicability

Addressess the relevant biological domain(s) of applicability in terms of sex, life-stage, taxa, and other aspects of biological context. More help

Essentiality of the Key Events

The essentiality of KEs can only be assessed relative to the impact of manipulation of a given KE (e.g., experimentally blocking or exacerbating the event) on the downstream sequence of KEs defined for the AOP. Consequently, evidence supporting essentiality is assembled on the AOP page, rather than on the independent KE pages that are meant to stand-alone as modular units without reference to other KEs in the sequence. The nature of experimental evidence that is relevant to assessing essentiality relates to the impact on downstream KEs and the AO if upstream KEs are prevented or modified. This includes: Direct evidence: directly measured experimental support that blocking or preventing a KE prevents or impacts downstream KEs in the pathway in the expected fashion. Indirect evidence: evidence that modulation or attenuation in the magnitude of impact on a specific KE (increased effect or decreased effect) is associated with corresponding changes (increases or decreases) in the magnitude or frequency of one or more downstream KEs. More help

Evidence Assessment

Addressess the biological plausibility, empirical support, and quantitative understanding from each KER in an AOP. More help

Known Modulating Factors

Modulating factors (MFs) may alter the shape of the response-response function that describes the quantitative relationship between two KES, thus having an impact on the progression of the pathway or the severity of the AO.The evidence supporting the influence of various modulating factors is assembled within the individual KERs. More help

Quantitative Understanding

Optional field to provide quantitative weight of evidence descriptors. More help

Considerations for Potential Applications of the AOP (optional)

Addressess potential applications of an AOP to support regulatory decision-making.This may include, for example, possible utility for test guideline development or refinement, development of integrated testing and assessment approaches, development of (Q)SARs / or chemical profilers to facilitate the grouping of chemicals for subsequent read-across, screening level hazard assessments or even risk assessment. More help

References

List of the literature that was cited for this AOP. More help