In silico tracking of SARS-CoV-2 Nsp1 structural variants in helix-turn-helix motif

SARS-CoV-2 non-structural protein 1 (Nsp1) is a virulence factor that inhibits the innate immune response and translation of host mRNAs. Despite the relevance of Nsp1, few studies have been conducted to understand the effect of mutations on Nsp1 structure and function. Here, we provide a molecular dynamics simulation of SARS-CoV-2 and SARS-CoV-1 Nsp1 conformational changes. Our data supports the idea that SARS-CoV-2 Nsp1 has a less compact structure than SARS-CoV-1 Nsp1. Moreover, several mutations in the helix-loop-helix motif of Nsp1 C-terminal that may affect the interactions of the Nsp1-ribosome complex were investigated. Disordered regions in Nsp1 probably affect host-virus interactions, cross-species transmission, and virus-host range. Overall, these findings reinforce the importance of studying Nsp1 conformational changes in new variants and its effect on virulence of SARS-CoV-2, by altering inhibition potency of host mRNA translation efficiency.

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Molecular Dynamics of SARS-CoV-2 Nsp1 Structural Changes Associated with Variant Mutations

10.21203/rs.3.rs-781636/v1 ◽

2021 ◽

Author(s):

Shokouh Rezaei ◽

Yahya Sefidbakht ◽

Filipe Pereira

Keyword(s):

Molecular Dynamics ◽

Conformational Changes ◽

Structural Changes ◽

Structure And Function ◽

Dynamics Simulation ◽

Structural Protein ◽

Wild Type ◽

Deletion Mutations ◽

And Function

Abstract SARS-CoV-2 non-structural protein 1 (Nsp1) is a virulence factor that inhibits the translation of host mRNAs and interact with viral RNA. Despite the relevance of Nsp1, few studies have been conducted to understand the effect of mutations on Nsp1 structure and function. Here, we provide a molecular dynamics simulation of SARS-CoV-2 Nsp1, wild type and variants. We found that SARS-CoV-2 Nsp1 has a more Rg value than SARS-CoV-1 Nsp1, with indicate an effect on the folding protein. This result suggest that SARS-CoV-2 Nsp1 can more easily approach the active site of the ribosome compared to SARS-CoV-1 Nsp1. In addition, we found that the C-terminal of the SARS-CoV-2 Nsp1, in particular residues 164 to 170, are more flexible than other regions of SARS-CoV-2 Nsp1 and SARS-CoV-1 Nsp1, confirming the role of this region in the interaction with the 40S subunit. Moreover, multiple deletion mutations have been found in the N/C-terminal of the SARS-CoV-2 Nsp1, which seems the effect of SARS-CoV-2 Nsp1 multiple deletions is greater than that of substitutions. Among all deletions, D156-158 and D80-90 may destabilize the protein structure and possibly increase the virulence of the SARS-CoV-2. Overall, our findings reinforce the importance of studying Nsp1 conformational changes in new variants and its effect on virulence of SARS-CoV-2.

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The Construction of Chimeric T-Cell Receptor with Spacer Base of Modeling Study of VHH and MUC1 Interaction

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/578128 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Nazanin Pirooznia ◽

Sadegh Hasannia ◽

Majid Taghdir ◽

Fatemeh Rahbarizadeh ◽

Morteza Eskandani

Keyword(s):

Root Mean Square ◽

Conformational Changes ◽

Cell Receptor ◽

Dynamics Simulation ◽

Specific Response ◽

Conformational Structure ◽

Mean Square ◽

Chimeric Receptors ◽

Cell Immunotherapy ◽

And Function

Adaptive cell immunotherapy with the use of chimeric receptors leads to the best and most specific response against tumors. Chimeric receptors consist of a signaling fragment, extracellular spacer, costimulating domain, and an antibody. Antibodies cause immunogenicity; therefore, VHH is a good replacement for ScFv in chimeric receptors. Since peptide sequences have an influence on chimeric receptors, the effect of peptide domains on each other's conformation were investigated. CD3Zeta, CD28, VHH and CD8α, and FcgIIα are used as signaling moieties, costimulating domain, antibody, and spacers, respectively. To investigate the influence of the ligation of spacers on the conformational structure of VHH, models of VHH were constructed. Molecular dynamics simulation was run to study the influence of the presence of spacers on the conformational changes in the binding sites of VHH. Root mean square deviation and root mean square fluctuation of critical segments in the binding site showed no noticeable differences with those in the native VHH. Results from molecular docking revealed that the presence of spacer FcgIIα causes an increasing effect on VHH with MUC1 interaction. Each of the constructs was transformed into the Jurkat E6.1. Expression analysis and evaluation of their functions were examined. The results showed good expression and function.

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Unraveling the Underlying Interaction Mechanism Between Dabie bandavirus and Innate Immune Response

Frontiers in Immunology ◽

10.3389/fimmu.2021.676861 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chuan-min Zhou ◽

Xue-jie Yu

Keyword(s):

Interaction Mechanism ◽

Innate Immune ◽

Type I ◽

Innate Immune Responses ◽

Structural Protein ◽

Antiviral Responses ◽

Host Virus Interactions ◽

Virus Interactions ◽

Severe Fever

The genus Bandavirus consists of seven tick-borne bunyaviruses, among which four are known to infect humans. Dabie bandavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), poses serious threats to public health worldwide. SFTSV is a tick-borne virus mainly reported in China, South Korea, and Japan with a mortality rate of up to 30%. To date, most immunology-related studies focused on the antagonistic role of SFTSV non-structural protein (NSs) in sequestering RIG-I-like-receptors (RLRs)-mediated type I interferon (IFN) induction and type I IFN mediated signaling pathway. It is still elusive whether the interaction of SFTSV and other conserved innate immune responses exists. As of now, no specific vaccines or therapeutics are approved for SFTSV prevention or treatments respectively, in part due to a lack of comprehensive understanding of the molecular interactions occurring between SFTSV and hosts. Hence, it is necessary to fully understand the host-virus interactions including antiviral responses and viral evasion mechanisms. In this review, we highlight the recent progress in understanding the pathogenesis of SFTS and speculate underlying novel mechanisms in response to SFTSV infection.

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Restriction of Retroviral Replication by Tetherin/BST-2

Molecular Biology International ◽

10.1155/2012/424768 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Jason Hammonds ◽

Jaang-Jiun Wang ◽

Paul Spearman

Keyword(s):

Restriction Factor ◽

Initial Report ◽

Host Restriction ◽

Host Restriction Factor ◽

Infected Cells ◽

Important Host ◽

Retroviral Replication ◽

Host Virus Interactions ◽

And Function ◽

Virus Interactions

Tetherin/BST-2 is an important host restriction factor that limits the replication of HIV and other enveloped viruses. Tetherin is a type II membrane glycoprotein with a very unusual domain structure that allows it to engage budding virions and retain them on the plasma membrane of infected cells. Following the initial report identifying tetherin as the host cell factor targeted by the HIV-1 Vpu gene, knowledge of the molecular, structural, and cellular biology of tetherin has rapidly advanced. This paper summarizes the discovery and impact of tetherin biology on the HIV field, with a focus on recent advances in understanding its structure and function. The relevance of tetherin to replication and spread of other retroviruses is also reviewed. Tetherin is a unique host restriction factor that is likely to continue to provide new insights into host-virus interactions and illustrates well the varied ways by which host organisms defend against viral pathogens.

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Integrative In Silico Investigation Reveals the Host-Virus Interactions in Repurposed Drugs Against SARS-CoV-2

Frontiers in Bioinformatics ◽

10.3389/fbinf.2021.763540 ◽

2022 ◽

Vol 1 ◽

Author(s):

Wenhui Yu ◽

Yuxin Bai ◽

Arjun Raha ◽

Zhi Su ◽

Fei Geng

Keyword(s):

Molecular Docking ◽

Drug Targets ◽

Interaction Network ◽

Dynamics Simulation ◽

Search Tool ◽

Direct Binding ◽

Repurposed Drugs ◽

Interaction Map ◽

Host Virus Interactions ◽

Virus Interactions

The ongoing COVID-19 outbreak have posed a significant threat to public health worldwide. Recently Toll-like receptor (TLR) has been proposed to be the drug target of SARS-CoV-2 treatment, the specificity and efficacy of such treatments remain unknown. In the present study we performed the investigation of repurposed drugs via a framework comprising of Search Tool for Interacting Chemicals (STITCH), Kyoto Encyclopedia of Genes and Genomes (KEGG), molecular docking, and virus-host-drug interactome mapping. Chloroquine (CQ) and hydroxychloroquine (HCQ) were utilized as probes to explore the interaction network that is linked to SARS-CoV-2. 47 drug targets were shown to be overlapped with SARS-CoV-2 network and were enriched in TLR signaling pathway. Molecular docking analysis and molecular dynamics simulation determined the direct binding affinity of TLR9 to CQ and HCQ. Furthermore, we established SARS-CoV-2-human-drug protein interaction map and identified the axis of TLR9-ERC1-Nsp13 and TLR9-RIPK1-Nsp12. Therefore, the elucidation of the interactions of SARS-CoV-2 with TLR9 axis will not only provide pivotal insights into SARS-CoV-2 infection and pathogenesis but also improve the treatment against COVID-19.

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Protein-induced conformational changes in 16S rRNA during assembly of the Escherichia Coli 30S ribosomal subunit: A STEM study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100128833 ◽

1987 ◽

Vol 45 ◽

pp. 910-911

Author(s):

M. Boublik ◽

V. Mandiyan ◽

J.F. Hainfeld ◽

J.S. Wall

Keyword(s):

16S Rrna ◽

Conformational Changes ◽

Ribosomal Proteins ◽

Structural Changes ◽

Ribosomal Subunit ◽

Compact Structure ◽

E Coli ◽

Freeze Dried ◽

16S Rna ◽

30S Subunit

The aim of this study is to understand the mechanism of 16S rRNA folding into the compact structure of the small 30S subunit of E. coli ribosome. The assembly of the 30S E. coli ribosomal subunit is a sequence of specific interactions of 16S rRNA with 21 ribosomal proteins (S1-S21). Using dedicated high resolution STEM we have monitored structural changes induced in 16S rRNA by the proteins S4, S8, S15 and S20 which are involved in the initial steps of 30S subunit assembly. S4 is the first protein to bind directly and stoichiometrically to 16S rRNA. Direct binding also occurs individually between 16S RNA and S8 and S15. However, binding of S20 requires the presence of S4 and S8. The RNA-protein complexes are prepared by the standard reconstitution procedure, dialyzed against 60 mM KCl, 2 mM Mg(OAc)2, 10 mM-Hepes-KOH pH 7.5 (Buffer A), freeze-dried and observed unstained in dark field at -160°.

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Host-virus interactions: Lessons from the model organismDrosophila melanogaster

10.1603/ice.2016.92693 ◽

2016 ◽

Author(s):

Jean-Luc Imler

Keyword(s):

Host Virus Interactions ◽

Virus Interactions

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Temporal mRNA Translation Efficiency Is Encoded In Viral Coding Regions

10.31988/scitrends.4648 ◽

2017 ◽

Author(s):

Tamir Tuller

Keyword(s):

Mrna Translation ◽

Translation Efficiency ◽

Coding Regions

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Influence of Ascorbic Acid on the Structure and Function of Alpha-2- macroglobulin: Investigations using Spectroscopic and Thermodynamic Techniques

Protein and Peptide Letters ◽

10.2174/0929866526666191002113525 ◽

2020 ◽

Vol 27 (3) ◽

pp. 201-209

Author(s):

Syed Saqib Ali ◽

Mohammad Khalid Zia ◽

Tooba Siddiqui ◽

Haseeb Ahsan ◽

Fahim Halim Khan

Keyword(s):

Ascorbic Acid ◽

Conformational Changes ◽

Structural Changes ◽

The Body ◽

Titration Calorimetry ◽

Spectroscopic Techniques ◽

Human Beings ◽

Plasma Ascorbic Acid ◽

Dietary Antioxidant ◽

And Function

Background: Ascorbic acid is a classic dietary antioxidant which plays an important role in the body of human beings. It is commonly found in various foods as well as taken as dietary supplement. Objective: The plasma ascorbic acid concentration may range from low, as in chronic or acute oxidative stress to high if delivered intravenously during cancer treatment. Sheep alpha-2- macroglobulin (α2M), a human α2M homologue is a large tetrameric glycoprotein of 630 kDa with antiproteinase activity, found in sheep’s blood. Methods: In the present study, the interaction of ascorbic acid with alpha-2-macroglobulin was explored in the presence of visible light by utilizing various spectroscopic techniques and isothermal titration calorimetry (ITC). Results: UV-vis and fluorescence spectroscopy suggests the formation of a complex between ascorbic acid and α2M apparent by increased absorbance and decreased fluorescence. Secondary structural changes in the α2M were investigated by CD and FT-IR spectroscopy. Our findings suggest the induction of subtle conformational changes in α2M induced by ascorbic acid. Thermodynamics signatures of ascorbic acid and α2M interaction indicate that the binding is an enthalpy-driven process. Conclusion: It is possible that ascorbic acid binds and compromises antiproteinase activity of α2M by inducing changes in the secondary structure of the protein.

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