Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A structural view of the SARS-CoV-2 virus and its assembly.

ABSTRACT: The SARS-CoV-2 pandemic that struck in 2019 has left the world crippled with hundreds of millions of cases and millions of people dead. During this time, we have seen unprecedented support and collaboration amongst scientists to respond to this deadly disease. Advances in the field of structural biology, in particular cryoEM and cryo-electron tomography, have allowed unprecedented structural analysis of SARS-CoV-2. Here, we review the structural work on the SARS-CoV-2 virus and viral components, as well as its cellular assembly process, highlighting some important structural findings that have made significant impact on the protection from and treatment of emerging viral infections.

SUBMITTER: Hardenbrook NJ

PROVIDER: S-EPMC8642146 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A structural view of the SARS-CoV-2 virus and its assembly.

Hardenbrook Nathan J NJ Zhang Peijun P

Current opinion in virology 20211204

The SARS-CoV-2 pandemic that struck in 2019 has left the world crippled with hundreds of millions of cases and millions of people dead. During this time, we have seen unprecedented support and collaboration amongst scientists to respond to this deadly disease. Advances in the field of structural biology, in particular cryoEM and cryo-electron tomography, have allowed unprecedented structural analysis of SARS-CoV-2. Here, we review the structural work on the SARS-CoV-2 virus and viral components, ...[more]

PMID: 34915287

Similar Datasets

Mechanosensing view of SARS-CoV-2 infection by a DNA nano-assembly.

Project description:The mechanical force between a virus and its host cell plays a critical role in viral infection. However, characterization of the virus-cell mechanical force at the whole-virus level remains a challenge. Herein, we develop a platform in which the virus is anchored with multivalence-controlled aptamers to achieve transfer of the virus-cell mechanical force to a DNA tension gauge tether (Virus-TGT). When the TGT is ruptured, the complex of binding module-virus-cell is detached from the substrate, accompanied by decreased host cell-substrate adhesion, thus revealing the mechanical force between whole-virus and cell. Using Virus-TGT, direct evidence about the biomechanical force between SARS-CoV-2 and the host cell is obtained. The relative mechanical force gap (<10 pN) at the cellular level between the wild-type virus to cell and a variant virus to cell is measured, suggesting a possible positive correlation between virus-cell mechanical force and infectivity. Overall, this strategy provides a new perspective to probe the SARS-CoV-2 mechanical force.

| S-EPMC9490855 | biostudies-literature

Heat shock protein 90 facilitates SARS-CoV-2 structural protein-mediated virion assembly and promotes virus-induced pyroptosis.

Project description:Inhibition of heat shock protein 90 (Hsp90), a prominent molecular chaperone, effectively limits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but little is known about any interaction between Hsp90 and SARS-CoV-2 proteins. Here, we systematically analyzed the effects of the chaperone isoforms Hsp90α and Hsp90β on individual SARS-CoV-2 viral proteins. Five SARS-CoV-2 proteins, namely nucleocapsid (N), membrane (M), and accessory proteins Orf3, Orf7a, and Orf7b were found to be novel clients of Hsp90β in particular. Pharmacological inhibition of Hsp90 with 17-DMAG results in N protein proteasome-dependent degradation. Hsp90 depletion-induced N protein degradation is independent of CHIP, a ubiquitin E3 ligase previously identified for Hsp90 client proteins, but alleviated by FBXO10, an E3 ligase identified by subsequent siRNA screening. We also provide evidence that Hsp90 depletion may suppress SARS-CoV-2 assembly partially through induced M or N degradation. Additionally, we found that GSDMD-mediated pyroptotic cell death triggered by SARS-CoV-2 was mitigated by inhibition of Hsp90. These findings collectively highlight a beneficial role for targeting of Hsp90 during SARS-CoV-2 infection, directly inhibiting virion production and reducing inflammatory injury by preventing the pyroptosis that contributes to severe SARS-CoV-2 disease.

| S-EPMC10066589 | biostudies-literature

Structure of SARS-CoV-2 membrane protein essential for virus assembly.

Project description:The coronavirus membrane protein (M) is the most abundant viral structural protein and plays a central role in virus assembly and morphogenesis. However, the process of M protein-driven virus assembly are largely unknown. Here, we report the cryo-electron microscopy structure of the SARS-CoV-2 M protein in two different conformations. M protein forms a mushroom-shaped dimer, composed of two transmembrane domain-swapped three-helix bundles and two intravirion domains. M protein further assembles into higher-order oligomers. A highly conserved hinge region is key for conformational changes. The M protein dimer is unexpectedly similar to SARS-CoV-2 ORF3a, a viral ion channel. Moreover, the interaction analyses of M protein with nucleocapsid protein (N) and RNA suggest that the M protein mediates the concerted recruitment of these components through the positively charged intravirion domain. Our data shed light on the M protein-driven virus assembly mechanism and provide a structural basis for therapeutic intervention targeting M protein.

| S-EPMC9355944 | biostudies-literature

Minimal system for assembly of SARS-CoV-2 virus like particles.

Project description:SARS-CoV-2 virus is the causative agent of COVID-19. Here we demonstrate that non-infectious SARS-CoV-2 virus like particles (VLPs) can be assembled by co-expressing the viral proteins S, M and E in mammalian cells. The assembled SARS-CoV-2 VLPs possess S protein spikes on particle exterior, making them ideal for vaccine development. The particles range in shape from spherical to elongated with a characteristic size of 129 ± 32 nm. We further show that SARS-CoV-2 VLPs dried in ambient conditions can retain their structural integrity upon repeated scans with Atomic Force Microscopy up to a peak force of 1 nN.

| S-EPMC7736577 | biostudies-literature

A Structural View of SARS-CoV-2 RNA Replication Machinery: RNA Synthesis, Proofreading and Final Capping.

Project description:The current coronavirus disease-2019 (COVID-19) pandemic is due to the novel coronavirus SARS-CoV-2. The scientific community has mounted a strong response by accelerating research and innovation, and has quickly set the foundation for understanding the molecular determinants of the disease for the development of targeted therapeutic interventions. The replication of the viral genome within the infected cells is a key stage of the SARS-CoV-2 life cycle. It is a complex process involving the action of several viral and host proteins in order to perform RNA polymerization, proofreading and final capping. This review provides an update of the structural and functional data on the key actors of the replicatory machinery of SARS-CoV-2, to fill the gaps in the currently available structural data, which is mainly obtained through homology modeling. Moreover, learning from similar viruses, we collect data from the literature to reconstruct the pattern of interactions among the protein actors of the SARS-CoV-2 RNA polymerase machinery. Here, an important role is played by co-factors such as Nsp8 and Nsp10, not only as allosteric activators but also as molecular connectors that hold the entire machinery together to enhance the efficiency of RNA replication.

| S-EPMC7291026 | biostudies-literature

SARS-CoV-2 annotated assembly

Project description:SARS-CoV-2 annotated assembly

| PRJEB42415 | ENA

Tick-Borne Encephalitis Virus: A Structural View.

Project description:Tick-borne encephalitis virus (TBEV) is a growing health concern. It causes a severe disease that can lead to permanent neurological complications or death and the incidence of TBEV infections is constantly rising. Our understanding of TBEV’s structure lags behind that of other flaviviruses, but has advanced recently with the publication of a high-resolution structure of the TBEV virion. The gaps in our knowledge include: aspects of receptor binding, replication and virus assembly. Furthermore, TBEV has mostly been studied in mammalian systems, even though the virus’ interaction with its tick hosts is a central part of its life cycle. Elucidating these aspects of TBEV biology are crucial for the development of TBEV antivirals, as well as the improvement of diagnostics. In this review, we summarise the current structural knowledge on TBEV, bringing attention to the current gaps in our understanding, and propose further research that is needed to truly understand the structural-functional relationship of the virus and its hosts.

| S-EPMC6071267 | biostudies-literature

Structural understanding of SARS-CoV-2 virus entry to host cells.

Project description:Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health concern associated with millions of fatalities worldwide. Mutant variants of the virus have further exacerbated COVID-19 mortality and infection rates, emphasizing the urgent need for effective preventive strategies. Understanding the viral infection mechanism is crucial for developing therapeutics and vaccines. The entry of SARS-CoV-2 into host cells is a key step in the infection pathway and has been targeted for drug development. Despite numerous reviews of COVID-19 and the virus, there is a lack of comprehensive reviews focusing on the structural aspects of viral entry. In this review, we analyze structural changes in Spike proteins during the entry process, dividing the entry process into prebinding, receptor binding, proteolytic cleavage, and membrane fusion steps. By understanding the atomic-scale details of viral entry, we can better target the entry step for intervention strategies. We also examine the impacts of mutations in Spike proteins, including the Omicron variant, on viral entry. Structural information provides insights into the effects of mutations and can guide the development of therapeutics and vaccines. Finally, we discuss available structure-based approaches for the development of therapeutics and vaccines. Overall, this review provides a detailed analysis of the structural aspects of SARS-CoV-2 viral entry, highlighting its significance in the development of therapeutics and vaccines against COVID-19. Therefore, our review emphasizes the importance of structural information in combating SARS-CoV-2 infection.

| S-EPMC10683510 | biostudies-literature

Structures from "Engineering Neutralizing SARS-CoV Antibodies to Bind SARS-CoV-2"

Project description: Not available

| S-BSST379 | biostudies-other

Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle

Project description: Not available

| EMPIAR-10999 | biostudies-other