scholarly journals Identification and Characterization of novel mutants of Nsp13 Protein among Indian SARS-CoV-2 isolates.

2021 ◽  
Author(s):  
Deepa Kumari ◽  
Namrata Kumari ◽  
Sudhir Kumar ◽  
Prabhat Kumar Sinha ◽  
Shivendra Kumar Shahi ◽  
...  
Keyword(s):  
B Cell ◽  
Protein Function ◽  
Protein Sequences ◽  
Structural Protein ◽  
Immunological Parameters ◽  
B Cell Epitopes ◽  
Global Challenge ◽  
Indian Isolates ◽  
And Function ◽  
The Impact

SARS-CoV-2, the causative agent of COVID-19 has mutated rapidly which enabled them to adapt and evade the immune system of the host. Emerging SARS-CoV-2 variants with crucial mutations pose a global challenge in context of therapeutic drugs and vaccines being developed globally. There are currently no specific therapeutics or vaccines available to combat SARS-CoV-2 devastation. In view of this, the current study aimed to identify and characterize the mutations found in the Nsp13 of SARS-CoV-2 in Indian isolates. Non-structural protein, Nsp13 protein sequences from Indian isolates were analyzed by comparing with the first reported Severe acute respiratory syndrome Corona Virus-2 (SARS-CoV-2) protein sequence from Wuhan, China. Out of 825 Nsp13 protein sequences, a total of 38 mutations were observed among Indian isolates. Our data show that mutations in Nsp13 at various positions (H164Y, A237T, T214I, C309Y, S236I, P419S, V305E, G54S, H290Y, P53S, A308Y, and A308Y) have a significant impact on the protein's stability and flexibility. Also, the impact of Nsp13 mutations on the protein function were predicted based on PROVEAN score that includes 15 mutants as neutral and 23 mutants as deleterious effect. Furthermore, B-cell epitopes contributed by Nsp13 were identified using various predictive immunoinformatic tools. Immunological Parameters of Nsp13 such as antigenicity, allergenicity and toxicity were evaluated to predict the potential B-cell epitopes. The predicted peptide sequences were correlated with the observed mutants. Our predicted data showed that there are seven high rank linear epitopes as well as 18 discontinuous B-cell epitopes based on immunoinformatic tools. Moreover, it was observed that out of total 38 identified mutations among Indian SARS-CoV-2 Nsp13 protein, four mutant residues at position 142 (E142), 245 (H245), 247 (V247) and 419 (P419) are localised in the predicted B cell epitopic region. Altogether, the results of the present in-silico study might help to understand the impact of the identified mutations in Nsp13 protein on its stability, flexibility and function.

scholarly journals SARS-CoV-2 and ORF3a: Non-Synonymous Mutations and Polyproline Regions

2020 ◽  
Author(s):  
Elio Issa ◽  
Georgi Merhi ◽  
Balig Panossian ◽  
Tamara Salloum ◽  
Sima Tokajian
Keyword(s):  
Amino Acids ◽  
Immune Response ◽  
B Cell ◽  
Immune Evasion ◽  
Protein Sequences ◽  
B Cell Epitopes ◽  
Synonymous Mutations ◽  
Viral Spread ◽  
Rapid Accumulation ◽  
The Impact

AbstractThe effect of the rapid accumulation of non-synonymous mutations on the pathogenesis of SARS-CoV-2 is not yet known. To predict the impact of non-synonymous mutations and polyproline regions identified in ORF3a on the formation of B-cell epitopes and their role in evading the immune response, nucleotide and protein sequences of 537 available SARS-CoV-2 genomes were analyzed for the presence of non-synonymous mutations and polyproline regions. Mutations were correlated with changes in epitope formation. A total of 19 different non-synonymous amino acids substitutions were detected in ORF3a among 537 SARS-CoV-2 strains. G251V was the most common and identified in 9.9% (n=53) of the strains and was predicted to lead to the loss of a B-cell like epitope in ORF3a. Polyproline regions were detected in two strains (EPI_ISL_410486, France and EPI_ISL_407079, Finland) and affected epitopes formation. The accumulation of non-synonymous mutations and detected polyproline regions in ORF3a of SARS-CoV-2 could be driving the evasion of the host immune response thus favoring viral spread. Rapid mutations accumulating in ORF3a should be closely monitored throughout the COVID-19 pandemic.ImportanceAt the surge of the COVID-19 pandemic and after three months of the identification of SARS-CoV-2 as the disease-causing pathogen, nucleic acid changes due to host-pathogen interactions are insightful into the evolution of this virus. In this paper, we have identified a set of non-synonymous mutations in ORF3a and predicted their impact on B-cell like epitope formation. The accumulation of non-synonymous mutations in ORF3a could be driving protein changes that mediate immune evasion and favoring viral spread.

B-cell and T-cell values in peripheral blood in Polish mixed-breed rabbits with addition of blood of meet breeds

2014 ◽  
Vol 17 (3) ◽  
pp. 421-426 ◽  
Author(s):  
B. Tokarz-Deptuła ◽  
P. Niedźwiedzka-Rystwej ◽  
B. Hukowska-Szematowicz ◽  
M. Adamiak ◽  
A. Trzeciak-Ryczek ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Laboratory Animals ◽  
Immunological Parameters ◽  
Four Seasons ◽  
Mixed Breed ◽  
The Impact

Abstract In Poland, rabbit is a highly valued animal, due to dietetic and flavour values of its meat, but above all, rabbits tend to be commonly used laboratory animals. The aim of the study was developing standards for counts of B-cells with CD19+ receptor, T-cells with CD5+ receptor, and their subpopulations, namely T-cells with CD4+, CD8+ and CD25+ receptor in the peripheral blood of mixed-breed Polish rabbits with addition of blood of meet breeds, including the assessment of the impact of four seasons of the year and animal sex on the values of the immunological parameters determined. The results showed that the counts of B- and T-cells and their subpopulations in peripheral blood remain within the following ranges: for CD19+ B-cells: 1.05 - 3.05%, for CD5+ T-cells: 34.00 - 43.07%, CD4+ T-cells: 23.52 - 33.23%, CD8+ T-cells: 12.55 - 17.30%, whereas for CD25+ T-cells: 0.72 - 2.81%. As it comes to the season of the year, it was observed that it principally affects the values of CD25+ T-cells, while in the case of rabbit sex, more changes were found in females.

Identification of three linear B cell epitopes against non-structural protein 3ABC of FMDV using monoclonal antibodies

2019 ◽  
Vol 103 (19) ◽  
pp. 8075-8086
Author(s):  
Wei Liu ◽  
Junjun Shao ◽  
Danian Chen ◽  
Yanyan Chang ◽  
Huiyun Chang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Structural Protein ◽  
B Cell Epitopes ◽  
Linear B

scholarly journals RETRACTED: Prediction and Identification of B-Cell Epitopes on Goose Parvovirus Non-structural Protein

2011 ◽  
Vol 8 ◽  
pp. 289-293
Author(s):  
Tian-fei Yu ◽  
Ming Li ◽  
Yuan Guo ◽  
Guang-jun Song ◽  
Rong-xiu Li ◽  
...  
Keyword(s):  
B Cell ◽  
Structural Protein ◽  
B Cell Epitopes ◽  
Goose Parvovirus

Localization of linear B-cell epitopes on goose parvovirus structural protein

2012 ◽  
Vol 145 (1-2) ◽  
pp. 522-526 ◽  
Author(s):  
Tian-fei Yu ◽  
Bo Ma ◽  
Ming-chun Gao ◽  
Jun-wei Wang
Keyword(s):  
B Cell ◽  
Structural Protein ◽  
B Cell Epitopes ◽  
Goose Parvovirus ◽  
Linear B

scholarly journals Vermont: a multi-perspective visual interactive platform for mutational analysis

2017 ◽  
Author(s):  
Alexandre V Fassio ◽  
Pedro M Martins ◽  
Samuel da S Guimarães ◽  
Sócrates S A Junior ◽  
Vagner S Ribeiro ◽  
...  
Keyword(s):  
Protein Function ◽  
Visual Analytics ◽  
Large Scale ◽  
Mutational Analysis ◽  
Structural Parameters ◽  
Point Mutations ◽  
Huge Amount ◽  
Interactive Visualizations ◽  
And Function ◽  
The Impact

AbstractBackgroundA huge amount of data about genomes and sequence variation is available and continues to grow on a large scale, which makes experimentally characterizing these mutations infeasible regarding disease association and effects on protein structure and function. Therefore, reliable computational approaches are needed to support the understanding of mutations and their impacts. Here, we present VERMONT 2.0, a visual interactive platform that combines sequence and structural parameters with interactive visualizations to make the impact of protein point mutations more understandable.ResultsWe aimed to contribute a novel visual analytics oriented method to analyze and gain insight on the impact of protein point mutations. To assess the ability of VERMONT to do this, we visually examined a set of mutations that were experimentally characterized to determine if VERMONT could identify damaging mutations and why they can be considered so.ConclusionsVERMONT allowed us to understand mutations by interpreting position-specific structural and physicochemical properties. Additionally, we note some specific positions we believe have an impact on protein function/structure in the case of mutation.

scholarly journals Single-molecule and Single-cell Approaches in Molecular Bioengineering

2020 ◽  
Vol 74 (9) ◽  
pp. 704-709
Author(s):  
Michael A. Nash
Keyword(s):  
Single Molecule ◽  
Protein Function ◽  
High Throughput Screening ◽  
Protein Sequences ◽  
Structural Features ◽  
Functional Protein ◽  
Molecular Systems ◽  
Measurement Tools ◽  
And Function ◽  
Control Protein

Protein sequences inhabit a discrete set in macromolecular space with incredible capacity to treat human disease. Despite our ability to program and manipulate protein sequences, the vast majority of protein development efforts are still done heuristically without a unified set of guiding principles. This article highlights work in understanding biophysical stability and function of proteins, developing new biophysical measurement tools and building high-throughput screening platforms to explore functional protein sequences. We highlight two primary areas. First, molecular biomechanics is a subfield concerned with the response of proteins to mechanical forces, and how we can leverage mechanical force to control protein function. The second subfield investigates the use of polymers and hydrogels in protein engineering and directed evolution in pursuit of new molecular systems with therapeutic applications. These two subdisciplines complement each other by shedding light onto sequence and structural features that can be used to impart stability into therapeutic proteins.

scholarly journals Activated PIK3CD drives innate B cell expansion yet limits B cell–intrinsic immune responses

2018 ◽  
Vol 215 (10) ◽  
pp. 2485-2496 ◽  
Author(s):  
Michelle N. Wray-Dutra ◽  
Fahd Al Qureshah ◽  
Genita Metzler ◽  
Mohamed Oukka ◽  
Richard G. James ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Plasma Cells ◽  
Recurrent Infection ◽  
Vaccine Responses ◽  
And Function ◽  
Natural Igm ◽  
The Impact

Activated PI3K-delta syndrome (APDS) is an immunodeficiency caused by gain-of-function mutations in PIK3CD. This disease exhibits complex immune phenotypes including increased IgM, recurrent infection, and impaired vaccine responses. To better understand the impact of B cells in this disease, we generated an inducible model of the common APDS mutation (hPIK3CD-E1021K; referred to as aPIK3CD) and intercrossed these mice with B cell–specific Cre models. Mb1-aPIK3CD mice exhibited bone marrow B lymphopenia and, conversely, expansion of the peripheral innate B1a and MZ B cell compartments. aPIK3CD B cells manifest increased pS6 and increased survival at several stages, without alterations in cycling, and baseline increases in plasma cells, natural IgM, and IgG3. Finally, Mb1-aPIK3CD mice exhibited blunted T cell–independent immune responses, and both AID- and CD21-aPIK3CD mice displayed reduced class-switched antibodies following T cell–dependent immunization. Thus, aPIK3CD alters B cell development and function and is counter-productive during immune responses, providing insight into B cell–intrinsic contributions to the APDS phenotype.

SELECTION OF CRYPTIC B-CELL EPITOPES USING INFORMATIONAL ANALYSIS OF PROTEIN SEQUENSES

2006 ◽  
Vol 04 (02) ◽  
pp. 389-402 ◽  
Author(s):  
ELENA SVIRSHCHEVSKAYA ◽  
LUDMILA ALEKSEEVA ◽  
ALEXEI MARCHENKO ◽  
SERGEI BENEVOLENSKII ◽  
VALENTINA M. BERZHEC ◽  
...  
Keyword(s):  
B Cell ◽  
Information Structure ◽  
Cell Epitope ◽  
Protein Sequences ◽  
Major Protein ◽  
Protein Antigens ◽  
B Cell Epitopes ◽  
Fel D 1 ◽  
B Cell Epitope ◽  
Selection Of

Sub-unit vaccines are synthetic or recombinant peptides representing T- or B-cell epitopes of major protein antigens from a particular pathogen. Epitope selection requires the synthesis of peptides that overlap the protein sequences and screening for the most effective ones. In this study a new method of immunogenic peptide selection based on the analysis of information structure of protein sequences is suggested. The analysis of known B-cell epitope location in the information structure of Aspergillus fumigatus proteins Asp f 2 and Asp f 3 has shown that epitopes are scattered along the sequences of proteins for the exception of sites with Increased Degree Information Coordination (IDIC). Based on these results peptides from different allergens such as Asp f 2, Der p 1, and Fel d 1 were selected and produced in a recombinant form in the context of yeast virus-like particles (VLPs). Immunization of mice with VLPs containing peptides form allergens has induced the production of IgG able to recognize full-length antigens. This result suggests that the analysis of information structure of proteins can be used for the selection of peptides possessing cryptic B-cell epitope activity.

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