Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Contributions of single-particle cryoelectron microscopy toward fighting COVID-19.

ABSTRACT: Single-particle cryoelectron microscopy (cryo-EM), whose full capabilities have been realized only within the past decade, has had a pivotal role in the fight against COVID-19. This is due to the technique's intrinsic power to depict both structural and dynamic features of molecules; in this case, of the spike protein of SARS-CoV-2. By now, numerous cryo-EM studies have furthered our understanding of spike protein-angiotensin-converting enzyme 2 (ACE2) receptor interactions, which has informed the design of effective vaccines, and have enabled the characterization of neutralizing antibody binding sites, which will lead to the design of novel therapeutics as the virus evolves.

SUBMITTER: Rapp M

PROVIDER: S-EPMC8556535 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Contributions of single-particle cryoelectron microscopy toward fighting COVID-19.

Rapp Micah M Shapiro Lawrence L Frank Joachim J

Trends in biochemical sciences 20211030 2

Single-particle cryoelectron microscopy (cryo-EM), whose full capabilities have been realized only within the past decade, has had a pivotal role in the fight against COVID-19. This is due to the technique's intrinsic power to depict both structural and dynamic features of molecules; in this case, of the spike protein of SARS-CoV-2. By now, numerous cryo-EM studies have furthered our understanding of spike protein-angiotensin-converting enzyme 2 (ACE2) receptor interactions, which has informed t ...[more]

PMID: 34799235

Similar Datasets

Determining structures in a native environment using single-particle cryoelectron microscopy images.

Project description:Cryo-electron tomography is a powerful tool for structure determination in the native environment. However, this method requires the acquisition of tilt series, which is time-consuming and severely slows structure determination. By treating the densities of non-target protein as non-Gaussian noise, we developed a new target function that greatly improves the efficiency of recognizing the target protein in a single cryo-electron microscopy image. Moreover, we developed a sorting function that effectively eliminates the model dependence and improved the resolution during the subsequent structure refinement procedure. By eliminating model bias, our method allows using homolog proteins as models to recognize the target proteins in a complex context. Together, we developed an in situ single-particle analysis method. Our method was successfully applied to solve structures of glycoproteins on the surface of a non-icosahedral virus and Rubisco inside the carboxysome. Both data were collected within 24 h, thus allowing fast and simple structural determination.

| S-EPMC8488058 | biostudies-literature

Single-particle cryoelectron microscopy analysis reveals the HIV-1 spike as a tripod structure.

Project description:The HIV-1 spike is a trimer of the transmembrane gp41 and the peripheral gp120 subunit pair. It is activated for virus-cell membrane fusion by binding sequentially to CD4 and to a chemokine receptor. Here we have studied the structural transition of the trimeric spike during the activation process. We solubilized and isolated unliganded and CD4-bound spikes from virus-like particles and used cryoelectron microscopy to reconstruct their 3D structures. In order to increase the yield and stability of the spike, we used an endodomain deleted and gp120-gp41 disulfide-linked variant. The unliganded spike displayed a hollow cage-like structure where the gp120-gp41 protomeric units formed a roof and bottom, and separated lobes and legs on the sides. The tripod structure was verified by fitting the recent atomic core structure of gp120 with intact N- and C-terminal ends into the spike density map. This defined the lobe as gp120 core, showed that the legs contained the polypeptide termini, and suggested the deleted variable loops V1/V2 and V3 to occupy the roof and gp41 the bottom. CD4 binding shifted the roof density peripherally and condensed the bottom density centrally. Fitting with a V3 containing gp120 core suggested that the V1/V2 loops in the roof were displaced laterally and the V3 lifted up, while the core and leg were kept in place. The loop displacements probably prepared the spike for coreceptor interaction and roof opening so that a new fusion-active gp41 structure, assembled at the center of the cage bottom, could reach the target membrane.

| S-EPMC2973878 | biostudies-literature

Single-Particle Resolution Fluorescence Microscopy of Nanoplastics.

Project description:Understanding of nanoplastic prevalence and toxicology is limited by imaging challenges resulting from their small size. Fluorescence microscopy is widely applied to track and identify microplastics in laboratory studies and environmental samples. However, conventional fluorescence microscopy, due to diffraction, lacks the resolution to precisely localize nanoplastics in tissues, distinguish them from free dye, or quantify them in environmental samples. To address these limitations, we developed techniques to label nanoplastics for imaging with stimulated emission depletion (STED) microscopy to achieve resolution at an order of magnitude superior to conventional fluorescence microscopy. These techniques include (1) passive sorption; (2) swell incorporation; and (3) covalent coupling of STED-compatible fluorescence dyes to nanoplastics. We demonstrate that our labeling techniques, combined with STED microscopy, can be used to resolve nanoplastics of different shapes and compositions as small as 50 nm. The longevity of dye labeling is demonstrated in different media and conditions of biological and environmental relevance. We also test STED imaging of nanoplastics in exposure experiments with the model worm Caenorhabditis elegans. Our work shows the value of the method for detection and localization of nanoplastics as small as 50 nm in a whole animal without disruption of the tissue. These techniques will allow more precise localization and quantification of nanoplastics in complex matrices such as biological tissues in exposure studies.

| S-EPMC9118545 | biostudies-literature

Fighting COVID-19 Using Molecular Dynamics Simulations.

Project description: Not available

| S-EPMC7571292 | biostudies-literature

Interaction of complexes I, III, and IV within the bovine respirasome by single particle cryoelectron tomography.

Project description:The respirasome is a multisubunit supercomplex of the respiratory chain in mitochondria. Here we report the 3D reconstruction of the bovine heart respirasome, composed of dimeric complex III and single copies of complex I and IV, at about 2.2-nm resolution, determined by cryoelectron tomography and subvolume averaging. Fitting of X-ray structures of single complexes I, III(2), and IV with high fidelity allows interpretation of the model at the level of secondary structures and shows how the individual complexes interact within the respirasome. Surprisingly, the distance between cytochrome c binding sites of complexes III(2) and IV is about 10 nm. Modeling indicates a loose interaction between the three complexes and provides evidence that lipids are gluing them at the interfaces.

| S-EPMC3174662 | biostudies-literature

Single-Particle Tracking with Scanning Non-Linear Microscopy.

Project description:This study describes the adaptation of non-linear microscopy for single-particle tracking (SPT), a method commonly used in biology with single-photon fluorescence. Imaging moving objects with non-linear microscopy raises difficulties due to the scanning process of the acquisitions. The interest of the study is based on the balance between all the experimental parameters (objective, resolution, frame rate) which need to be optimized to record long trajectories with the best accuracy and frame rate. To evaluate the performance of the setup for SPT, several basic estimation methods are used and adapted to the new detection process. The covariance-based estimator (CVE) seems to be the best way to evaluate the diffusion coefficient from trajectories using the specific factors of motion blur and localization error.

| S-EPMC7466504 | biostudies-literature

A primer to single-particle cryo-electron microscopy.

Project description:Cryo-electron microscopy (cryo-EM) of single-particle specimens is used to determine the structure of proteins and macromolecular complexes without the need for crystals. Recent advances in detector technology and software algorithms now allow images of unprecedented quality to be recorded and structures to be determined at near-atomic resolution. However, compared with X-ray crystallography, cryo-EM is a young technique with distinct challenges. This primer explains the different steps and considerations involved in structure determination by single-particle cryo-EM to provide an overview for scientists wishing to understand more about this technique and the interpretation of data obtained with it, as well as a starting guide for new practitioners.

| S-EPMC4409659 | biostudies-literature

Comprehensive Overview on Multiple Strategies Fighting COVID-19.

Project description:Lately, myriad of novel viruses have emerged causing epidemics such as SARS, MERS, and SARS-CoV-2, leading to high mortality rates worldwide. Thus, these viruses represented a challenging threat to mankind, especially considering the miniscule data available at our disposal regarding these novel viruses. The entire world established coordinative relations in research projects regarding drug and vaccine development on the external range, whereas on the internal range, all countries declared it an emergency case through imposing different restrictions related to their border control, large gatherings, school attendance, and most social activities. Pandemic combating plans prioritized all sectors including normal people, medical staff politicians, and scientists collectively shouldered the burden. Through planning and learning the previous lessons from SARS and MERS, healthcare systems could succeed in combating the viral spread and implications of these new pandemics. Different management strategies including social distance, social awareness and isolation represented successful ways to slow down the spread of the pandemic. Furthermore, pre-preparedness of some countries for emergencies is crucial to minimize the consequences of the crisis.

| S-EPMC7460286 | biostudies-literature

Approaches towards fighting the COVID‑19 pandemic (Review).

Project description:The coronavirus disease 2019 (COVID‑19) outbreak, which has caused >46 millions confirmed infections and >1.2 million coronavirus related deaths, is one of the most devastating worldwide crises in recent years. Infection with COVID‑19 results in a fever, dry cough, general fatigue, respiratory symptoms, diarrhoea and a sore throat, similar to those of acute respiratory distress syndrome. The causative agent of COVID‑19, SARS‑CoV‑2, is a novel coronavirus strain. To date, remdesivir has been granted emergency use authorization for use in the management of infection. Additionally, several efficient diagnostic tools are being actively developed, and novel drugs and vaccines are being evaluated for their efficacy as therapeutic agents against COVID‑19, or in the prevention of infection. The present review highlights the prevalent clinical manifestations of COVID‑19, characterizes the SARS‑CoV‑2 viral genome sequence and life cycle, highlights the optimal methods for preventing viral transmission, and discusses possible molecular pharmacological mechanisms and approaches in the development of anti‑SARS‑CoV‑2 therapeutic agents. In addition, the use of traditional Chinese medicines for management of COVID‑19 is discussed. It is expected that novel anti‑viral agents, vaccines or an effective combination therapy for treatment/management of SARS‑CoV‑2 infection and spread therapy will be developed and implemented in 2021, and we would like to extend our best regards to the frontline health workers across the world in their fight against COVID‑19.

| S-EPMC7723515 | biostudies-literature

COVID-19: fighting the invisible enemy with microRNAs.

Project description:IntroductionThe novel coronavirus (CoV) disease 2019 (COVID-19) is a viral infection that causes severe acute respiratory syndrome (SARS). It is believed that early reports of COVID-19 cases were noticed in December 2019 and soon after it became a global public health emergency. It is advised that COVID-19 transmits through human to human contact and in most cases, it remains asymptomatic. Several approaches are being utilized to control the outbreak of this fatal viral disease. microRNAs (miRNAs) are known signature therapeutic tool for the viral diseases; they are small non-coding RNAs that target the mRNAs to inhibit their post-transcriptional expression, therefore, impeding their functions, can serve as watchdogs or micromanagers in the cells.Areas coveredThis review work delineated COVID-19 and its association with SARS and Middle East respiratory syndrome (MERS), the possible role of miRNAs in the pathogenesis of COVID-19, and therapeutic potential of miRNAs and their effective delivery to treat COVID-19.Expert opinionThis review highlighted the importance of various miRNAs and their potential role in fighting with this pandemic as therapeutic molecules utilizing nanotechnology.

| S-EPMC7870525 | 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