Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ACE2 isoform diversity predicts the host susceptibility of SARS-CoV-2.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19) pandemic. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2. In our current study, we found that two types of deficient ACE2 isoforms from different mammals compete with full-length ACE2 for association with S protein. One type of ACE2 is a natural soluble isoform, the other type of ACE2 only associates with one loop of the receptor-binding domain (RBD) of the SARS-CoV-2 S protein. Mammals with either type of ACE2 will be deficient in support of SARS-CoV-2 entry. By combining S recognition and isoform analysis of ACE2, we predict that felids, mustelids, hamsters, and sheep are susceptible to SARS-CoV-2, while canids, swines, cattle, and goats are not permissive for SARS-CoV-2. Thus, the differential susceptibilities of mammals with SARS-CoV-2 infection could be partially explained by the ACE2 isoform diversity. Our findings will shed important light on predicting the host range of other zoonotic viruses.

SUBMITTER: Gao S

PROVIDER: S-EPMC7436438 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection.

Project description:SARS-CoV-2 causes the recent global COVID-19 public health emergency. ACE2 is the receptor for both SARS-CoV-2 and SARS-CoV. To predict the potential host range of SARS-CoV-2, we analyzed the key residues of ACE2 for recognizing S protein. We found that most of the selected mammals including pets (dog and cat), pangolin and Circetidae mammals remained the most of key residues for association with S protein from SARS-CoV and SARS-CoV-2. The interaction interface between cat/dog/pangolin/Chinese hamster ACE2 and SARS-CoV/SARS-CoV-2 S protein was simulated through homology modeling. We identified that N82 in ACE2 showed a closer contact with SARS-CoV-2 S protein than M82 in human ACE2. Our finding will provide important insights into the host range of SARS-CoV-2 and a new strategy to design an optimized ACE2 for SARS-CoV-2 infection.

| S-EPMC7102515 | biostudies-literature

Integrate structural analysis, isoform diversity, and interferon-inductive propensity of ACE2 to predict SARS-CoV2 susceptibility in vertebrates.

Project description:The current new coronavirus disease (COVID-19) has caused globally over 0.4/6 million confirmed deaths/infected cases across more than 200 countries. As the etiological coronavirus (a.k.a. SARS-CoV2) may putatively have a bat origin, our understanding about its intermediate reservoir between bats and humans, especially its tropism in wild and domestic animals are mostly unknown. This constitutes major concerns in public health for the current pandemics and potential zoonosis. Previous reports using structural analysis of the viral spike protein (S) binding its cell receptor of angiotensin-converting enzyme 2 (ACE2), indicate a broad potential of SARS-CoV2 susceptibility in wild and particularly domestic animals. Through integration of key immunogenetic factors, including the existence of S-binding-void ACE2 isoforms and the disparity of ACE2 expression upon early innate immune response, we further refine the SARS-CoV2 susceptibility prediction to fit recent experimental validation. In addition to showing a broad susceptibility potential across mammalian species based on structural analysis, our results also reveal that domestic animals including dogs, pigs, cattle and goats may evolve ACE2-related immunogenetic diversity to restrict SARS-CoV2 infections. Thus, we propose that domestic animals may be unlikely to play a role as amplifying hosts unless the virus has further species-specific adaptation. Findings may relieve relevant public concerns regarding COVID-19-like risk in domestic animals, highlight virus-host coevolution, and evoke disease intervention through targeting ACE2 molecular diversity and interferon optimization.

| S-EPMC7458074 | biostudies-literature

mouse ACE2 receptor bound to SARS-CoV-2 variant Beta Spike

Project description: Not available

| EMPIAR-11181 | biostudies-other

Vitamin C promotes ACE2 degradation and protects against SARS-CoV-2 infection

Project description:ACE2 is a major receptor for cellular entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2 binding, strategies to flexibly and sufficiently reduce ACE2 levels for the prevention of SARS-CoV-2 infection have not been explored. Here, we reveal vitamin C (VitC) administration as a potent strategy to prevent SARS-CoV-2 infection. VitC reduces ACE2 protein levels in a dose-dependent manner, while even a partial reduction in ACE2 levels can greatly inhibit SARS-CoV-2 infection. Further studies reveal that USP50 is a crucial regulator of ACE2 levels. VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination of ACE2 at Lys788 and subsequent degradation of ACE2 without affecting its transcriptional expression. Importantly, VitC administration reduces host ACE2 levels and greatly blocks SARS-CoV-2 infection in mice. This study reveals that ACE2 protein levels are down-regulated by an essential nutrient, VitC, thereby enhancing protection against infection of SARS-CoV-2 and its variants.

| S-SCDT-10_15252-EMBR_202256374 | biostudies-other

Missense variants in human ACE2 modify binding to SARS-CoV-2 Spike

Project description: Not available

| S-BSST649 | biostudies-other

In silico analysis of ACE2 orthologues to predict animal host range with high susceptibility to SARS-CoV-2.

Project description:SARS-CoV-2, which causes severe pneumonia epidemics, probably originated from Chinese horseshoe bats, but the intermediate and host range is still unknown. ACE2 is the entry receptor for SARS-CoV-2. The binding capacity of SARS-CoV-2 spike protein to ACE2 is the critical determinant of viral host range and cross-species infection. Here, we used an in silico approach to predict the potential animals range with high susceptibility to SARS-CoV-2 by modelling and studying the Spike-ACE2 interaction of 22 domestic and wild animals. Our results showed that all studied animals are potentially susceptible to SARS-CoV-2 infection with a slight difference in the binding affinity and stability of their ACE2-RBD complexes. Furthermore, we identified a specific substitution of tyrosine to histidine at position 41 in ACE2 that likely reduces the affinity to SARS-CoV-2 in horses and greater horseshoe bats. These results may help to provide important insights into SARS-CoV-2 host range which will make it possible to control the spread of the virus and identify animal models that could be used for screening antiviral drugs or vaccine candidates against SARS-CoV-2.

| S-EPMC7577366 | biostudies-literature

mouse ACE2 receptor bound to SARS-CoV-2 variant Omicron BA.2.12.1 Spike

Project description: Not available

| EMPIAR-11180 | biostudies-other

mouse ACE2 receptor bound to SARS-CoV-2 variant Omicron BA.1 Spike

Project description: Not available

| EMPIAR-11179 | biostudies-other

Can ACE2 Receptor Polymorphism Predict Species Susceptibility to SARS-CoV-2?

Project description:A novel severe acute respiratory syndrome coronavirus, SARS-CoV-2, emerged in China in December 2019 and spread worldwide, causing more than 1.3 million deaths in 11 months. Similar to the human SARS-CoV, SARS-CoV-2 shares strong sequence homologies with a sarbecovirus circulating in Rhinolophus affinis bats. Because bats are expected to be able to transmit their coronaviruses to intermediate animal hosts that in turn are a source of viruses able to cross species barriers and infect humans (so-called spillover model), the identification of an intermediate animal reservoir was the subject of intense researches. It was claimed that a reptile (Ophiophagus hannah) was the intermediate host. This hypothesis was quickly ruled out and replaced by the pangolin (Manis javanica) hypothesis. Yet, pangolin was also recently exonerated from SARS-CoV-2 transmission to humans, leaving other animal species as presumed guilty. Guided by the spillover model, several laboratories investigated in silico the species polymorphism of the angiotensin I converting enzyme 2 (ACE2) to find the best fits with the SARS-CoV-2 spike receptor-binding site. Following the same strategy, we used multi-sequence alignment, 3-D structure analysis, and electrostatic potential surface generation of ACE2 variants to predict their binding capacity to SARS-CoV-2. We report evidence that such simple in silico investigation is a powerful tool to quickly screen which species are potentially susceptible to SARS-CoV-2. However, possible receptor binding does not necessarily lead to successful replication in host. Therefore, we also discuss here the limitations of these in silico approaches in our quest on the origins of COVID-19 pandemic.

| S-EPMC7902720 | biostudies-literature

Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2.

Project description:COVID-19 is a respiratory illness caused by a novel coronavirus called SARS-CoV-2. The viral spike (S) protein engages the human angiotensin-converting enzyme 2 (ACE2) receptor to invade host cells with ~10-15-fold higher affinity compared to SARS-CoV S-protein, making it highly infectious. Here, we assessed if ACE2 polymorphisms can alter host susceptibility to SARS-CoV-2 by affecting this interaction. We analyzed over 290,000 samples representing >400 population groups from public genomic datasets and identified multiple ACE2 protein-altering variants. Using reported structural data, we identified natural ACE2 variants that could potentially affect virus-host interaction and thereby alter host susceptibility. These include variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R that were predicted to increase susceptibility, while variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y were predicted to be protective variants that show decreased binding to S-protein. Using biochemical assays, we confirmed that K31R and E37K had decreased affinity, and K26R and T92I variants showed increased affinity for S-protein when compared to wildtype ACE2. Consistent with this, soluble ACE2 K26R and T92I were more effective in blocking entry of S-protein pseudotyped virus suggesting that ACE2 variants can modulate susceptibility to SARS-CoV-2.

| S-EPMC8041869 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data