Browse
Submit Data
Databases
API
Help

Dataset Information

6 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections.

ABSTRACT: Enterovirus D68 (EV-D68) is an emerging pathogen associated with respiratory diseases and/or acute flaccid myelitis. Here, two MAbs, 2H12 and 8F12, raised against EV-D68 virus-like particle (VLP), show distinct preference in binding VLP and virion and in neutralizing different EV-D68 strains. A combination of 2H12 and 8F12 exhibits balanced and potent neutralization effects and confers broader protection in mice than single MAbs when given at onset of symptoms. Cryo-EM structures of EV-D68 virion complexed with 2H12 or 8F12 show that both antibodies bind to the canyon region of the virion, creating steric hindrance for sialic acid receptor binding. Additionally, 2H12 binding can impair virion integrity and trigger premature viral uncoating. We also capture an uncoating intermediate induced by 2H12 binding, not previously described for picornaviruses. Our study elucidates the structural basis and neutralizing mechanisms of the 2H12 and 8F12 MAbs and supports further development of the 2H12/8F12 cocktail as a broad-spectrum therapeutic agent against EV-D68 infections in humans.

SUBMITTER: Zhang C

PROVIDER: S-EPMC8131599 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections.

Project description:The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections.

| S-EPMC7801428 | biostudies-literature

Enterovirus D68 and Human Respiratory Infections.

Project description:Enterovirus D68 (EV-D68) is a member of the species Enterovirus D in the genus Enterovirus of the Picornaviridae family. EV-D68 was first isolated in the United States in 1962 and is primarily an agent of respiratory disease. Infections with EV-D68 have been rarely reported until recently, when reports of EV-D68 associated with respiratory disease increased notably worldwide. An outbreak in 2014 in the United States, for example, involved more than 1,000 cases of severe respiratory disease that occurred across almost all states. Phylogenetic analysis of all EV-D68 sequences indicates that the circulating strains of EV-D68 can be classified into two lineages, lineage 1 and lineage 2. In contrast to the prototype Fermon strain, all circulating strains have deletions in their genomes. Respiratory illness associated with EV-D68 infection ranges from mild illness that just needs outpatient service to severe illness requiring intensive care and mechanical ventilation. To date, there are no specific medicines and vaccines to treat or prevent EV-D68 infection. This review provides a detailed overview about our current understanding of EV-D68-related virology, epidemiology and clinical syndromes, pathogenesis, and laboratory diagnostics.

| S-EPMC7171721 | biostudies-literature

enterovirus D68

Project description:enterovirus D68 Genome sequencing and assembly

| PRJNA1078856 | ENA

Enterovirus D68

Project description:Complete Genome Sequences of Enterovirus D68 in the Philippines

| PRJDB11586 | ENA

Enterovirus D68

Project description:Enterovirus D68 Genome sequencing and assembly

| PRJNA274680 | ENA

Enterovirus D68

Project description:Enterovirus D68 sequence from clinical isolates (St. Louis, 2014)

| PRJNA263037 | ENA

enterovirus D68

Project description:enterovirus D68 Genome sequencing

| PRJNA900246 | ENA

Enterovirus D68

Project description:Enterovirus D68 Genome sequencing

| PRJNA266569 | ENA

Enterovirus D68 Infection.

Project description:First described in 1962 in children hospitalized for pneumonia and bronchiolitis, the Enterovirus D68 (EV-D68) is an emergent viral pathogen. Since its discovery, during the long period of surveillance up to 2005, EV-D68 was reported only as a cause of sporadic outbreaks. In recent years, many reports from different countries have described an increasing number of patients with respiratory diseases due to EV-D68 associated with relevant clinical severity. In particular, an unexpectedly high number of children have been hospitalized for severe respiratory disease due to EV-D68, requiring intensive care such as intubation and mechanical ventilation. Moreover, EV-D68 has been associated with acute flaccid paralysis and cranial nerve dysfunction in children, which has caused concerns in the community. As no specific antiviral therapy is available, treatment is mainly supportive. Moreover, because no vaccines are available, conventional infection control measures (i.e., standard, for contacts and droplets) in both community and healthcare settings are recommended. However, further studies are required to fully understand the real importance of this virus. Prompt diagnosis and continued surveillance of EV-D68 infections are essential to managing and preventing new outbreaks. Moreover, if the association between EV-D68 and severe diseases will be confirmed, the development of adequate preventive and therapeutic approaches are a priority.

| S-EPMC4664996 | biostudies-literature

Respiratory Infections by Enterovirus D68 in Outpatients and Inpatients Spanish Children.

Project description:The incidence of enterovirus D68 (EV-D68) and the spectrum of clinical disease in children are not well known in European countries. We have designed a study with the objective of describing the clinical impact of EV-D68 detected in children with respiratory tract infections.As a part of a prospective study to identify the etiology and clinical characteristics of viral respiratory infections in children in Spain, we performed the analysis of the cases of EV infections in all children hospitalized in a secondary hospital in Madrid, during the epidemic respiratory season 2012-2013. A second group of samples was corresponded to infants of the same area, with ambulatory respiratory infection or asymptomatic. Phylogenetic EV-D68 analysis was made using the viral protein 1 gene (VP1). Clinical data of EV-D68 patients were compared with those infected by rhinovirus in the same period and population.The study population consisted of 720 patients corresponding to 399 episodes of hospitalization for respiratory causes, 44 episodes of ambulatory respiratory infections and 277 children determined as a healthy control group. A total of 22 patients were positive for EVs (3.05%), and 12 of them were specifically typed as EV-D68 (11/443 respiratory infections, 2.5%). The most frequent diagnosis in the 10 hospitalized children with EV-D68 detection was recurrent wheezing. Hypoxia was present in 70% of cases, but admission in the intensive care unit was not required. No neurological signs or symptoms were observed. One patient had an ambulatory mild bronchiolitis and another was asymptomatic. No differences were found with rhinovirus infections except less duration of hypoxia and fever in EV-D68 group.EV-D68 infections were detected in 3.05% of respiratory studied samples (2.5% of admissions). The infection was associated with wheezing episodes with hypoxia. No admissions to intensive care unit or neurological symptoms were found.

| S-EPMC4677598 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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