The BioGRID database: A comprehensive biomedical resource of curated protein, genetic, and chemical interactions

Protein Science, Journal Year: 2020, Volume and Issue: 30(1), P. 187 - 200

Published: Oct. 18, 2020

The BioGRID (Biological General Repository for Interaction Datasets, thebiogrid.org) is an open-access database resource that houses manually curated protein and genetic interactions from multiple species including yeast, worm, fly, mouse, human. ~1.93 million in can be used to build complex networks facilitate biomedical discoveries, particularly as related human health disease. All content primary experimental evidence the literature, includes both focused low-throughput studies large high-throughput datasets. also captures post-translational modifications or gene with bioactive small molecules many known drugs. A built-in network visualization tool combines all annotations allows users generate graphs of protein, chemical interactions. In addition general curation across species, undertakes themed projects specific aspects cellular regulation, example ubiquitin-proteasome system, well disease areas, such SARS-CoV-2 virus causes COVID-19 severe acute respiratory syndrome. recent extension BioGRID, named Open CRISPR Screens (ORCS, orcs.thebiogrid.org), single mutant phenotypes published high throughput genome-wide CRISPR/Cas9-based screens. BioGRID-ORCS contains datasets over 1,042 screens carried out date human, mouse fly cell lines. research community freely access data through web interface, standardized file downloads, via model organism databases partner meta-databases.

Language: Английский

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Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 7, 2020

After the 1918 flu pandemic, world is again facing a similar situation. However, advancement in medical science has made it possible to identify that novel infectious agent from coronavirus family. Rapid genome sequencing by various groups helped predicting structure and function of virus, immunogenicity diverse populations its preventive measures. Coronavirus attacks respiratory system causing pneumonia lymphopenia infected individuals. Viral components like spike, nucleo-capsid proteins trigger an immune response host eliminate virus. These viral antigens can be either recognized B cells or presented MHC complexes T resulting antibody production, increased cytokine secretion cytolytic activity acute phase infection. Association HLA downregulated expression been correlated with disease severity against influenza coronaviruses. Studies have reported individuals after recovery induce strong protective responses generating memory cell pool SARS-CoV MERS-CoV. were not persistent for long term upon reactivation caused local damages due cross-reactivity. So far reports suggest SARS-CoV-2, which highly contagious shows related symptoms 3 different stages develops exhaustive higher loads As there are no specific treatments available this coronavirus, numerous small molecular drugs being used treatment diseases SARS, MERS, HIV, ebola, malaria tuberculosis under clinical trials controlling COVID-19. A classical immunotherapy convalescent plasma transfusion recovered patients also initiated neutralization viremia terminally ill COVID-19 patients. Due limitations transfusion, researchers now focusing on developing neutralizing antibodies virus particles along immuno-modulation cytokines such as IL-6, TNF-α interferons could help combating This review highlights similarities SARS-CoV, MERS-CoV SARS-CoV-2 relation their pathogenicity focuses strategies employed curing

Language: Английский

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A CRISPR/Cas12a-empowered surface plasmon resonance platform for rapid and specific diagnosis of the Omicron variant of SARS-CoV-2

National Science Review, Journal Year: 2022, Volume and Issue: 9(8)

Published: June 3, 2022

The outbreak of the COVID-19 pandemic was partially due to challenge identifying asymptomatic and presymptomatic carriers virus, thus highlights a strong motivation for diagnostics with high sensitivity that can be rapidly deployed. On other hand, several concerning SARS-CoV-2 variants, including Omicron, are required identified as soon samples 'positive'. Unfortunately, traditional PCR test does not allow their specific identification. Herein, first time, we have developed MOPCS (Methodologies Photonic CRISPR Sensing), which combines an optical sensing technology-surface plasmon resonance (SPR) 'gene scissors' clustered regularly interspaced short palindromic repeat (CRISPR) technique achieve both specificity when it comes measurement viral variants. is low-cost, CRISPR/Cas12a-system-empowered SPR gene-detecting platform analyze RNA, without need amplification, within 38 min from sample input results output, limit detection 15 fM. achieves highly sensitive analysis SARS-CoV-2, mutations appear in variants B.1.617.2 (Delta), B.1.1.529 (Omicron) BA.1 (a subtype Omicron). This also used some recently collected patient local China, by Centers Disease Control Prevention. innovative CRISPR-empowered will further contribute fast, accurate target nucleic acid sequences single-base mutations.

Language: Английский

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ACE2/ADAM17/TMPRSS2 Interplay May Be the Main Risk Factor for COVID-19

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Oct. 7, 2020

The Coronavirus Disease 2019 (COVID-19) has already caused hundreds of thousands deaths worldwide in a few months. Cardiovascular disease, hypertension, diabetes and chronic lung disease have been identified as the main COVID-19 comorbidities. Moreover, despite similar infection rates between men women, most severe course is higher elderly co-morbid male patients. Therefore, occurrence specific comorbidities associated with renin–angiotensin system (RAS) imbalance mediated by interaction angiotensin-converting enzyme 2 (ACE2) desintegrin metalloproteinase domain 17 (ADAM17), along genetic factors mainly type II transmembrane serine protease (TMPRSS2) expression, could be decisive for clinical outcome COVID-19. Indeed, exacerbated ADAM17 – ACE2, TNF-α IL-6R secretion emerges possible underlying mechanism acute inflammatory immune response activation coagulation cascade. this review, we focus on pathophysiological aspects TMPRSS2 host proteins Additionally, discuss to explain deleterious effect over-activation outcome.

Language: Английский

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Targeting SARS-CoV-2 Proteases and Polymerase for COVID-19 Treatment: State of the Art and Future Opportunities

Journal of Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 65(4), P. 2716 - 2746

Published: Nov. 13, 2020

The newly emerged coronavirus, called SARS-CoV-2, is the causing pathogen of pandemic COVID-19. identification drugs to treat COVID-19 and other coronavirus diseases an urgent global need, thus different strategies targeting either virus or host cell are still under investigation. Direct-acting agents, protease polymerase functionalities, represent a milestone in antiviral therapy. 3C-like (or Main) (3CLpro) nsp12 RNA-dependent RNA-polymerase (RdRp) best characterized SARS-CoV-2 targets show highest degree conservation across coronaviruses fostering broad-spectrum inhibitors. Coronaviruses also possess papain-like protease, another essential enzyme, poorly not equally conserved, limiting agents. Herein, we provide exhaustive comparative analysis proteases RdRp with respect homologues. Moreover, highlight most promising inhibitors these proteins reported so far, including possible for their further development.

Language: Английский

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Is the kidney a target of SARS-CoV-2?

AJP Renal Physiology, Journal Year: 2020, Volume and Issue: 318(6), P. F1454 - F1462

Published: May 15, 2020

The new disease produced by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) represents a major pandemic event nowadays. Since its origin in China December 2019, there is compelling evidence that novel SARS-CoV-2 highly transmissible virus, and it associated to broad clinical spectrum going from subclinical presentation distress multiorgan failure. Like other coronaviruses, recognizes human angiotensin-converting enzyme as cellular receptor allows infect different host cells likely disrupts renin-angiotensin-aldosterone system homeostasis. Particularly, considerable incidence of many renal abnormalities COVID-19 has been reported, including proteinuria, hematuria, kidney injury. Moreover, recently demonstrated can podocytes tubular epithelial cells, which could contribute the development aforementioned abnormalities. In this review, we discuss biological aspects infection, how understanding current knowledge about infection may partly explain involvement kidneys pathophysiology COVID-19, what questions have arisen remain be explored.

Language: Английский

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COVID-19 as an Acute Inflammatory Disease

The Journal of Immunology, Journal Year: 2020, Volume and Issue: 205(1), P. 12 - 19

Published: May 18, 2020

Abstract The 2019 coronavirus disease (COVID-19) pandemic caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has created an unprecedented global crisis for infrastructure sectors, including economic, political, healthcare, education, and research systems. Although over 90% of infected individuals are asymptomatic or manifest noncritical symptoms will recover from infection, those presenting with critical in urgent need effective treatment options. Emerging data related to mechanism severity potential therapies patients scattered therefore require a comprehensive analysis focus on developing therapeutics. A literature review suggests that SARS-CoV-2 infection is associated dysregulation inflammatory immune responses, which turn inhibits development protective immunity infection. Therefore, use therapeutics modulate inflammation without compromising adaptive response could be most therapeutic strategy.

Language: Английский

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Notch Signaling in Vascular Endothelial Cells, Angiogenesis, and Tumor Progression: An Update and Prospective

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Feb. 16, 2021

The Notch signaling pathway plays an essential role in a wide variety of biological processes including cell fate determination vascular endothelial cells and the regulation arterial differentiation angiogenesis. is also regulator tumor growth survival by functioning as either oncogene or suppressor context-dependent manner. Crosstalk between other pathways pivotal progression promoting cancer growth, migration, invasion, metastasis, angiogenesis, expansion stem (CSCs). In this review, we provide overview update functioning, progression, particularly development CSCs therapeutic resistance. We further summarize recent studies on how crosstalk with contributes to angiogenesis CSCs, thereby providing insights into biology within microenvironment progression.

Language: Английский

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The adaptive immune system is a major driver of selection for tumor suppressor gene inactivation

Science, Journal Year: 2021, Volume and Issue: 373(6561), P. 1327 - 1335

Published: Sept. 16, 2021

During tumorigenesis, tumors must evolve to evade the immune system and do so by disrupting genes involved in antigen processing presentation or up-regulating inhibitory checkpoint genes. We performed vivo CRISPR screens syngeneic mouse tumor models examine requirements for tumorigenesis both with without adaptive selective pressure. In each type tested, we found a marked enrichment loss of suppressor (TSGs) presence an relative immunocompromised mice. Nearly one-third TSGs showed preferential enrichment, often cancer- tissue-specific manner. These results suggest that clonal selection recurrent mutations cancer is driven largely tumor’s requirement avoid system.

Language: Английский

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Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 25, 2022

Despite the promise of immune checkpoint inhibition (ICI), therapeutic responses remain limited. This raises possibility that standard care treatments delivered in concert may compromise tumor response. To address this, we employ tobacco-signature head and neck squamous cell carcinoma murine models which map tumor-draining lymphatics develop for regional lymphablation with surgery or radiation. We find eliminates ICI response, worsening overall survival repolarizing tumor- peripheral-immune compartments. Mechanistically, within lymphatics, observe an upregulation conventional type I dendritic cells interferon signaling show both are necessary response lost lymphablation. Ultimately, provide a mechanistic understanding how oncologic therapies targeting impact to immune-oncology therapy order define rational, lymphatic-preserving treatment sequences mobilize systemic antitumor immunity, achieve optimal responses, control metastatic disease, confer durable immunity.

Language: Английский

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