Human cytokine and coronavirus nucleocapsid protein interactivity using large-scale virtual screens

Frontiers in Bioinformatics, Год журнала: 2024, Номер 4

Опубликована: Май 24, 2024

Understanding the interactions between SARS-CoV-2 and human immune system is paramount to characterization of novel variants as virus co-evolves with host. In this study, we employed state-of-the-art molecular docking tools conduct large-scale virtual screens, predicting binding affinities 64 cytokines against 17 nucleocapsid proteins from six betacoronaviruses. Our comprehensive in silico analyses reveal specific changes cytokine-nucleocapsid protein interactions, shedding light on potential modulators host response during infection. These findings offer valuable insights into mechanisms underlying viral pathogenesis may guide future development targeted interventions. This manuscript serves insight comparison deep learning based AlphaFold2-Multimer semi-physicochemical HADDOCK for protein-protein docking. We show two methods are complementary their predictive capabilities. also introduce a algorithm rapidly assessing interface docks using graph edit distance: graph-based residue assessment function (GIRAF). The high-performance computational framework presented here will not only aid accelerating discovery effective interventions emerging threats, but extend other applications high throughput screens.

Язык: Английский

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Molecular characterization of SARS-CoV-2 nucleocapsid protein

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Май 23, 2024

Corona Virus Disease 2019 (COVID-19) is a highly prevalent and potent infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Until now, the world still endeavoring to develop new ways diagnose treat COVID-19. At present, clinical prevention treatment of COVID-19 mainly targets spike protein on surface SRAS-CoV-2. However, with continuous emergence SARS-CoV-2 Variants concern (VOC), targeting therapy shows high degree limitation. The Nucleocapsid Protein (N protein) conserved in virus evolution involved key process viral infection assembly. It most expressed structural after humans has immunogenicity. Therefore, N as factor replication basic research application great potential value. This article reviews progress structure biological function protein, diagnosis drug order promote researchers’ further understanding lay theoretical foundation for possible outbreak sudden diseases future.

Язык: Английский

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Challenges in Emerging Vaccines and Future Promising Candidates against SARS-CoV-2 Variants

Journal of Immunology Research, Год журнала: 2024, Номер 2024, С. 1 - 19

Опубликована: Янв. 25, 2024

Since the COVID-19 outbreak, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus has evolved into variants with varied infectivity. Vaccines developed against infection have boosted immunity, but there is still uncertainty on how long immunity from natural or vaccination will last. The present study attempts to outline level of information about contagiousness and spread SARS-CoV-2 interest concern (VOCs). keywords like vaccine types, VOCs, universal vaccines, bivalent, other relevant terms were searched in NCBI, Science Direct, WHO databases review published literature. provides an integrative discussion current state knowledge type vaccines SARS-CoV-2, safety efficacy concerning prospects novel universal, chimeric, bivalent mRNA fend off existing emerging coronaviruses. Genomic variation can be quite significant, as seen by notable differences impact, transmission rate, morbidity, death during several human outbreaks. Therefore, understanding amount characteristics genetic diversity historical contemporary strains help researchers get edge over upcoming variants.

Язык: Английский

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Modulation of biophysical properties of nucleocapsid protein in the mutant spectrum of SARS-CoV-2

eLife, Год журнала: 2024, Номер 13

Опубликована: Июнь 28, 2024

Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage uniquely large genomic database SARS-CoV-2, we examine impact mutations across spectrum viable amino acid sequences on biophysical phenotypes highly expressed multifunctional nucleocapsid protein. We find variation in physicochemical parameters its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur related coronaviruses. In experiments with several N-protein species carrying associated major variants, point IDRs can have nonlocal modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, liquid-liquid phase separation. Omicron variant, distant different compensatory effects shifting delicate balance interactions controlling assembly properties, include creation new protein-protein interaction interface N-terminal IDR through defining P13L mutation. A picture emerges where genetic accompanied by significant characteristics species, particular IDRs.

Язык: Английский

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Unraveling the role of the nucleocapsid protein in SARS-CoV-2 pathogenesis: From viral life cycle to vaccine development

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 279, С. 135201 - 135201

Опубликована: Авг. 30, 2024

Язык: Английский

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SARS‐CoV‐2, aging, and Post‐COVID‐19 neurodegeneration

Journal of Neurochemistry, Год журнала: 2022, Номер 165(2), С. 115 - 130

Опубликована: Дек. 2, 2022

Abstract As the world continues to experience effects of SARS‐CoV‐2, there is evidence suggest that sequelae viral infection (the post‐COVID‐19 condition; PCC) at both an individual and population level will be significant long‐lasting. The history pandemics or epidemics in last 100 years caused by members RNA virus family, which coronaviruses are a member, provides ample acute neurological effects. However, except for H1N1 influenza pandemic 1918/1919 Spanish flu) with its associated encephalitis lethargica, little information on long‐term sequelae. COVID‐19 first has occurred setting aging population, especially several high‐income countries. Its survivors greatest risk developing neurodegenerative conditions as they age, rendering current unique paradigm not previously witnessed. SARS‐CoV‐2 virus, among largest viruses, single‐stranded encodes 29 proteins include spike protein contains key domains required ACE2 binding, complex array nonstructural (NSPs) accessory ensure escape from innate immune response, allowing efficient replication, translation, exocytosis fully functional virion. Increasingly, these also recognized potentially contributing biochemical molecular processes underlying neurodegeneration. In addition directly being taken up brain endothelium, constituents can transported neurons, astrocytes, microglia extracellular vesicles accelerate pathological fibril formation. nucleocapsid intrinsically disordered participate liquid condensate formation, including heteropolymers disease‐associated RNA‐binding such TDP‐43, FUS, hnRNP1A. mutate under pressure exerted highly efficacious vaccines, it evolving into greater transmissibility but less severity compared original strain. potential lingering impact nervous system thus represent ongoing legacy even global health challenge than infection. image

Язык: Английский

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Autoimmunity and Immunodeficiency in Severe SARS-CoV-2 Infection and Prolonged COVID-19

Current Issues in Molecular Biology, Год журнала: 2022, Номер 45(1), С. 33 - 50

Опубликована: Дек. 21, 2022

SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily affects respiratory system but can quickly become systemic, harming multiple organs leading to long-lasting sequelae in some patients. Most infected individuals are asymptomatic or present mild symptoms. Antibodies, complement, immune cells efficiently eliminate virus. However, 20% of develop severe organ failure. Virus replication has been described several patients who died from COVID-19, suggesting a compromised response. Immunodeficiency autoimmunity responsible for this impairment facilitate viral escape. Mutations IFN signal transduction T cell activation inadequate response young individuals. Autoantibodies accountable secondary immunodeficiency with infection prolonged Antibodies against cytokines (interferons α, γ ω, IL1β, IL6, IL10, IL-17, IL21), chemokines, nuclear proteins DNA, anticardiolipin, extracellular have reported. type titer autoantibodies depend on age gender. Organ-specific Their role is under study. Autoimmunity should be screened risk factors

Язык: Английский

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SARS‐CoV‐2 nucleocapsid: Biological functions and implication for disease diagnosis and vaccine design

Reviews in Medical Virology, Год журнала: 2023, Номер 33(3)

Опубликована: Фев. 15, 2023

The coronavirus disease 2019 (COVID-19) pandemic is transmitted by severe acute respiratory syndrome 2 (SARS-CoV-2) and has affected millions of people all around the world, leading to more than 6.5 million deaths. nucleocapsid (N) phosphoprotein plays important roles in modulating viral replication transcription, virus-infected cell cycle progression, apoptosis, regulation host innate immunity. As an immunodominant protein, N protein induces strong humoral cellular immune responses COVID-19 patients, making it a key marker for studying N-specific B T development diagnostic serological assays efficient vaccines. In this review, we focus on structural functional features kinetic epitope mapping against SARS-CoV-2 extend our understanding sensitive specific immunological tests effective

Язык: Английский

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The Key to Increase Immunogenicity of Next-Generation COVID-19 Vaccines Lies in the Inclusion of the SARS-CoV-2 Nucleocapsid Protein

Journal of Immunology Research, Год журнала: 2024, Номер 2024, С. 1 - 18

Опубликована: Май 29, 2024

Vaccination is one of the most effective prophylactic public health interventions for prevention infectious diseases such as coronavirus disease (COVID-19). Considering ongoing need new COVID-19 vaccines, it crucial to modify our approach and incorporate more conserved regions severe acute respiratory syndrome 2 (SARS-CoV-2) effectively address emerging viral variants. The nucleocapsid protein a structural SARS-CoV-2 that involved in replication immune responses. Furthermore, this offers significant advantages owing minimal accumulation mutations over time inclusion key T-cell epitopes critical immunity. A novel strategy may be suitable generation vaccines against use combination antigens, including spike proteins, elicit robust humoral potent cellular responses, along with long-lasting strategic multiple antigens aims enhance vaccine efficacy broaden protection viruses, their response from other long-lasting, can persist up 11 years post-infection. Thus, incorporation nucleocapsids (N) into design adds an important dimension vaccination efforts holds promise bolstering ability combat effectively. In review, we summarize preclinical studies evaluated antigen. This study discusses alone its or proteins SARS-CoV-2.

Язык: Английский

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Assessment of Immunogenic and Antigenic Properties of Recombinant Nucleocapsid Proteins of Five SARS-CoV-2 Variants in a Mouse Model

Viruses, Год журнала: 2023, Номер 15(1), С. 230 - 230

Опубликована: Янв. 13, 2023

COVID-19 cases caused by new variants of highly mutable SARS-CoV-2 continue to be identified worldwide. Effective control the spread can achieved through targeting conserved viral epitopes. In this regard, nucleocapsid (N) protein, which is much more than evolutionarily influenced spike protein (S), a suitable antigen. The recombinant N considered not only as screening antigen but also basis for development next-generation vaccines, little known about induction antibodies against via different variants. addition, it important understand how produced one variant react with proteins other Here, we used from five strains investigate their immunogenicity and antigenicity in mouse model obtain characterize panel hybridoma-derived monoclonal anti-N antibodies. We analyzed variable epitopes that are potentially involved differential recognition antiviral These results will further deepen our knowledge cross-reactivity humoral immune response COVID-19.

Язык: Английский

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