Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2.

ABSTRACT: While there is SARS-CoV-2 multiorgan tropism in severely infected COVID-19 patients, it's unclear if this occurs in healthy young individuals. In addition, for antibodies that target the spike protein (SP), it's unclear if these reduce SARS-CoV-2/SP multiorgan tropism equally. We used fluorescently labeled SP-NIRF to study viral behavior, using an in vivo dynamic imaging system and ex in vivo tissue analysis, in young mice. We found a SP body-wide biodistribution followed by a slow regional elimination, except for the liver, which showed an accumulation. SP uptake was highest for the lungs, and this was followed by kidney, heart and liver, but, unlike the choroid plexus, it was not detected in the brain parenchyma or CSF. Thus, the brain vascular barriers were effective in restricting the entry of SP into brain parenchyma in young healthy mice. While both anti-ACE2 and anti-SP antibodies suppressed SP biodistribution and organ uptake, anti-SP antibody was more effective. By extension, our data support the efficacy of these antibodies on SARS-CoV-2 multiorgan tropism, which could determine COVID-19 organ-specific outcomes.

SUBMITTER: Brady M

PROVIDER: S-EPMC8609008 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Neutralizing antibodies targeting SARS-CoV-2 spike protein.

Project description:SARS-CoV-2 causing the worldwide pandemic has changed people's life in multiple aspects dramatically since it's first identified in Wuhan, China at the end of 2019. While the numbers of infected patients and death toll keep vigorous increasing, curbing the progression of the pandemic is an urgent goal. Efforts have been made to search for prophylactic and therapeutic approaches including neutralizing antibodies development. By reviewing dozens of studies on anti-spike antibodies identification, we concluded that (1) promising therapeutic antibodies are being fished out by various approaches, such as screening of single B cells of convalescent patients, recombinant antibody library and B cells of immunized animals; (2) the epitopes are mainly RBD, but also some non-RBD domains, without the requisite of overlapping with ACE2 binding sites; (3) Neutralizing antibodies are convergent to a few germline genes, including IGHV3-30, IGHV3-53, IGHV3-66, with varying levels of somatic mutations. This review summarizes the progress in neutralizing antibodies development and the germline enrichment of effective antibodies, which will shed light on COVID-19 treatment and vaccine design.

| S-EPMC7737530 | biostudies-literature

SARS-CoV-2 cell tropism and multiorgan infection.

Project description: Not available

| S-EPMC7987126 | biostudies-literature

Therapeutic antibodies and fusion inhibitors targeting the spike protein of SARS-CoV-2.

Project description: Not available

| S-EPMC7544964 | biostudies-literature

Targeting the SARS-CoV-2-spike protein: from antibodies to miniproteins and peptides.

Project description:Coronavirus disease-19, caused by the novel β-coronavirus SARS-CoV-2, has created a global pandemic unseen in a century. Rapid worldwide efforts have enabled the characterization of the virus and its pathogenic mechanism. An early key finding is that SARS-CoV-2 uses spike proteins, the virus' most exposed structures, to bind to human ACE2 receptors and initiate cell invasion. Competitive targeting of the spike protein is a promising strategy to neutralize virus infectivity. This review article summarizes the discovery, binding modes and eventual applications of several classes of (bio)molecules targeting the spike protein: antibodies, nanobodies, soluble ACE2 variants, miniproteins, peptides and small molecules.

| S-EPMC8128053 | biostudies-literature

SARS-CoV-2 Spike Protein and Neutralizing Anti-Spike Protein Antibodies Modulate Blood Platelet Function.

Project description:Several studies report elevated blood platelet activation and altered platelet count in COVID-19 patients, but the role of the SARS-CoV-2 spike protein in this process remains intriguing. Additionally, there is no data that anti-SARS-CoV-2 neutralizing antibodies (nAb) may attenuate spike protein activity toward blood platelets. Our results indicate that under in vitro conditions, the spike protein increased the collagen-stimulated aggregation of isolated platelets and induced the binding of vWF to platelets in ristocetin-treated blood. The spike protein also significantly reduced collagen- or ADP-induced aggregation or decreased GPIIbIIIa (fibrinogen receptor) activation in whole blood, depending on the presence of the anti-spike protein nAb. Our findings suggest that studies on platelet activation/reactivity in COVID-19 patients or in donors vaccinated with anti-SARS-CoV-2 and/or previously-infected COVID-19 should be supported by measurements of spike protein and IgG anti-spike protein antibody concentrations in blood.

| S-EPMC10049216 | biostudies-literature

SARS-CoV-2 spike protein S:D614G + S:A222V variant

Project description: Not available

| EMPIAR-10891 | biostudies-other

The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins.

Project description:SARS Coronavirus 2 (SARS-CoV-2) emerged in late 2019, leading to the Coronavirus Disease 2019 (COVID-19) pandemic that continues to cause significant global mortality in human populations. Given its sequence similarity to SARS-CoV, as well as related coronaviruses circulating in bats, SARS-CoV-2 is thought to have originated in Chiroptera species in China. However, whether the virus spread directly to humans or through an intermediate host is currently unclear, as is the potential for this virus to infect companion animals, livestock, and wildlife that could act as viral reservoirs. Using a combination of surrogate entry assays and live virus, we demonstrate that, in addition to human angiotensin-converting enzyme 2 (ACE2), the Spike glycoprotein of SARS-CoV-2 has a broad host tropism for mammalian ACE2 receptors, despite divergence in the amino acids at the Spike receptor binding site on these proteins. Of the 22 different hosts we investigated, ACE2 proteins from dog, cat, and cattle were the most permissive to SARS-CoV-2, while bat and bird ACE2 proteins were the least efficiently used receptors. The absence of a significant tropism for any of the 3 genetically distinct bat ACE2 proteins we examined indicates that SARS-CoV-2 receptor usage likely shifted during zoonotic transmission from bats into people, possibly in an intermediate reservoir. Comparison of SARS-CoV-2 receptor usage to the related coronaviruses SARS-CoV and RaTG13 identified distinct tropisms, with the 2 human viruses being more closely aligned. Finally, using bioinformatics, structural data, and targeted mutagenesis, we identified amino acid residues within the Spike-ACE2 interface, which may have played a pivotal role in the emergence of SARS-CoV-2 in humans. The apparently broad tropism of SARS-CoV-2 at the point of viral entry confirms the potential risk of infection to a wide range of companion animals, livestock, and wildlife.

| S-EPMC7751883 | biostudies-literature

Analysis of the Neutralizing Activity of Antibodies Targeting Open or Closed SARS-CoV-2 Spike Protein Conformations.

Project description:SARS-CoV-2 infection elicits a polyclonal neutralizing antibody (nAb) response that primarily targets the spike protein, but it is still unclear which nAbs are immunodominant and what distinguishes them from subdominant nAbs. This information would however be crucial to predict the evolutionary trajectory of the virus and design future vaccines. To shed light on this issue, we gathered 83 structures of nAbs in complex with spike protein domains. We analyzed in silico the ability of these nAbs to bind the full spike protein trimer in open and closed conformations, and predicted the change in binding affinity of the most frequently observed spike protein variants in the circulating strains. This led us to define four nAb classes with distinct variant escape fractions. By comparing these fractions with those measured from plasma of infected patients, we showed that the class of nAbs that most contributes to the immune response is able to bind the spike protein in its closed conformation. Although this class of nAbs only partially inhibits the spike protein binding to the host's angiotensin converting enzyme 2 (ACE2), it has been suggested to lock the closed pre-fusion spike protein conformation and therefore prevent its transition to an open state. Furthermore, comparison of our predictions with mRNA-1273 vaccinated patient plasma measurements suggests that spike proteins contained in vaccines elicit a different nAb class than the one elicited by natural SARS-CoV-2 infection and suggests the design of highly stable closed-form spike proteins as next-generation vaccine immunogens.

| S-EPMC8876721 | biostudies-literature

Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.

Project description:Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor-binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.

| S-EPMC7723407 | biostudies-literature

SARS-CoV-2 spike protein (1-up RBD) on EG-grid

Project description: Not available

| EMPIAR-10951 | biostudies-other