A systematic review and meta-analysis: the effect of active cancer treatment on severity of COVID-19

European Journal of Cancer, Journal Year: 2020, Volume and Issue: 141, P. 92 - 104

Published: Oct. 6, 2020

The COVID-19 pandemic hit all over the world, and cancer patients are more vulnerable for COVID-19. mortality rate may increase up to 25% in solid malignancies. In parallel increased rates among patients, safety concerns regarding treatment has time. However, there were contradictory results during pandemic. this study, we assessed effect of on severity COVID-19.The MEDLINE database was searched September 01, 2020. Primary end-points severe disease death treated within last 30 days before diagnosis. Quality included studies by Newcastle-Ottawa scale. generic inverse-variance method used calculate odds ratios (ORs) each outcome.Sixteen meta-analysis. Chemotherapy thirty diagnosis risk after adjusting confounding variables (OR: 1.85; 95% confidence interval: 1.26-2.71). did not increase. Furthermore, targeted therapies, immunotherapy, surgery radiotherapy with COVID-19.Chemotherapy from patients. no concern radiotherapy.

Language: Английский

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Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication

Cell Reports, Journal Year: 2021, Volume and Issue: 35(1), P. 108940 - 108940

Published: March 19, 2021

SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified small-molecule library of 34 430 protein kinase inhibitors that were capable inhibiting cytopathic effect in human epithelial cells. These drug are various stages clinical trials. detected key proteins involved cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, DNA-damage response critical for infection. A drug-protein interaction-based secondary screen confirmed compounds, such as ATR inhibitor berzosertib torin2 with anti-SARS-CoV-2 activity. Berzosertib exhibited potent antiviral activity against multiple cell types blocked replication at post-entry step. inhibited SARS-CoV-1 Middle East respiratory syndrome coronavirus (MERS-CoV) well. Our study highlights promising to constrain host-directed therapy treatment beyond well provides an important mechanism host-pathogen interactions.

Language: Английский

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Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects

Journal of Endocrinological Investigation, Journal Year: 2021, Volume and Issue: 44(9), P. 1801 - 1814

Published: March 25, 2021

Abstract Background Thyroid dysfunction has been observed in patients with COVID-19, and endocrinologists are requested to understand this clinical issue. Pandemic-related restrictions reorganization of healthcare services may affect thyroid disease management. Objective methods To analyze discuss the relationship between COVID-19 diseases from several perspectives. PubMed/MEDLINE, Google Scholar, Scopus, ClinicalTrial.gov were searched for purpose by using free text words medical subject headings as follows: “sars cov 2”, “covid 19”, “subacute thyroiditis”, “atypical “chronic “hashimoto’s “graves’ disease”, “thyroid nodule”, “differentiated cancer”, “medullary “methimazole”, “levothyroxine”, “multikinase inhibitor”, “remdesivir”, “tocilizumab”. Data collected, analyzed, discussed answer following questions: “What evidence suggests that induce detrimental consequences on function?"; "Could previous or concomitant deteriorate prognosis once infection occurred?”; “Could management influence course COVID-19?”; “Does interfere function?”; “Are there defined strategies better manage endocrine despite restrictive measures in-hospital ambulatory activities reorganizations?”. Results SARS-CoV-2 is usually reversible, including subclinical atypical thyroiditis. Patients baseline not at higher risk contracting transmitting SARS-CoV-2, does foster a worse progression COVID-19. However, it unclear whether low levels triiodothyronine, seriously ill worsen disease's and, consequently, if triiodothyronine supplementation could be tool reducing burden. Glucocorticoids heparin hormone secretion measurement, respectively, leading possible misdiagnosis severe cases High-risk nodules require fine-needle aspiration without relevant delay, whereas other non-urgent diagnostic procedures therapeutic interventions should postponed. Discussion Currently, we know lead short-term reversible dysfunction, but seem Adequate remains essential during pandemic, compromised because service restrictions. Endocrine care centers continuously recognize classify priority in-person visits procedures. Telemedicine useful managing requiring visits.

Language: Английский

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Translational precision medicine: an industry perspective

Journal of Translational Medicine, Journal Year: 2021, Volume and Issue: 19(1)

Published: June 5, 2021

Abstract In the era of precision medicine, digital technologies and artificial intelligence, drug discovery development face unprecedented opportunities for product business model innovation, fundamentally changing traditional approach how drugs are discovered, developed marketed. Critical to this transformation is adoption new in process, catalyzing transition from serendipity-driven data-driven medicine. This paradigm shift comes with a need both translation precision, leading modern Translational Precision Medicine development. Key components multi-omics profiling, biomarkers, model-based data integration, intelligence , biomarker-guided trial designs patient-centric companion diagnostics. review, we summarize critically discuss potential challenges cross-industry perspective.

Language: Английский

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The roles of signaling pathways in SARS-CoV-2 infection; lessons learned from SARS-CoV and MERS-CoV

Archives of Virology, Journal Year: 2021, Volume and Issue: 166(3), P. 675 - 696

Published: Jan. 18, 2021

Language: Английский

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Connecting omics signatures and revealing biological mechanisms with iLINCS

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

Published: Aug. 9, 2022

There are only a few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses visualization do not require programming skills. Here we present iLINCS ( http://ilincs.org ), an web-based platform analysis of signatures cellular perturbations. The facilitates mining re-analysis the large collection datasets (>34,000), pre-computed (>200,000), their connections, as well user-submitted diseases workflows vast resources range analytics interactive tools into comprehensive signatures. user-friendly enable execution sophisticated signatures, mechanism action analysis, signature-driven drug repositioning. We illustrate utility with three use cases involving cancer proteogenomic COVID 19 transcriptomic mTOR signaling.

Language: Английский

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Kinases as Potential Therapeutic Targets for Anti-coronaviral Therapy

Journal of Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 65(2), P. 955 - 982

Published: June 3, 2021

The global coronavirus disease-19 (COVID-19) has affected more than 140 million and killed 3 people worldwide as of April 20, 2021. novel human severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) been identified an etiological agent for COVID-19. Several kinases have proposed possible mediators multiple viral infections, including life-threatening coronaviruses like SARS-CoV-1, Middle East (MERS-CoV), SARS-CoV-2. Viral infections hijack abundant cell signaling pathways, resulting in drastic phosphorylation rewiring the host proteins. Some play a significant role throughout infection cycle (entry, replication, assembly, egress), several them are involved virus-induced hyperinflammatory response that leads to cytokine storm, distress (ARDS), organ injury, death. Here, we highlight associated with their inhibitors antiviral potentially anti-inflammatory, cytokine-suppressive, or antifibrotic activity.

Language: Английский

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NF-κB Signaling and Inflammation—Drug Repurposing to Treat Inflammatory Disorders?

Biology, Journal Year: 2022, Volume and Issue: 11(3), P. 372 - 372

Published: Feb. 26, 2022

NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As result its role in so many important cellular processes, dysregulation has been implicated the pathology human diseases. activation causes inappropriate inflammatory responses diseases including rheumatoid arthritis (RA) multiple sclerosis (MS). Thus, modulation signaling being widely investigated as an approach treat chronic diseases, autoimmunity cancer. The emergence COVID-19 late 2019, subsequent pandemic huge clinical burden patients with life-threatening SARS-CoV-2 pneumonia led massive scramble repurpose existing medicines lung inflammation wide range healthcare systems. These efforts continue have proven be controversial. Drug repurposing strategies are promising alternative de novo drug development, they minimize development timelines reduce risk failure due unexpected side effects. Different experimental approaches applied identify which inhibit that could repurposed anti-inflammatory drugs.

Language: Английский

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A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19

COVID, Journal Year: 2022, Volume and Issue: 2(2), P. 148 - 167

Published: Jan. 26, 2022

Drug repurposing is a more inexpensive and shorter approach than the traditional drug discovery development process. The concept of identifying potent molecule from library pre-existing molecules or an already approved has become go-to tactic to accelerate identification drugs that can prevent COVID-19. This seemingly uncontrollable disease caused by SARS-CoV-2. It novel virus Betacoronavirus genus, exhibiting similarities previously reported SAR-CoV genome structure viral pathogenesis. emergence SARS-CoV-2 rapid outbreak COVID-19 have resulted in global pandemic. Researchers are hard-pressed develop new for total containment disease, thus making cost-effective much feasible approach. Therefore, current review attempts collate both experimental computational strategies been utilized against significant targets Along with strategies, available druggable shall also be discussed. However, occurrence frequent recombination time-bound primary analysis, resulting insignificant data, two major challenges still faces.

Language: Английский

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Estrogen hormone is an essential sex factor inhibiting inflammation and immune response in COVID-19

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: June 8, 2022

Although vaccines have been evaluated and approved for SARS-CoV-2 infection prevention, there remains a lack of effective treatments to reduce the mortality COVID-19 patients already infected with SARS-CoV-2. The global data on showed that men higher rate than women. We further observed proportion females increases starting from around age 55 significantly. Thus, sex is an essential factor associated mortality, related genetic factors could be interesting mechanisms targets treatment. However, signaling pathways remain unclear. Here, we propose uncover potential using systematic integrative network analysis. unique results indicated estrogens, e.g., estrone estriol, (1) interacting ESR1/2 receptors, (2) can inhibit caused inflammation immune response in host cells; (3) estrogens are distinct fatality rates between male female patients. Specifically, high level estradiol protects young patients, drop extremely low after about years causing increased In conclusion, estrogen, death by inhibiting infection. Moreover, medications boosting down-stream ESR1/ESR2, or immune-associated potentially synergistic combined other existing drugs

Language: Английский

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