Potential therapeutic options for COVID-19: an update on current evidence

European journal of medical research, Journal Year: 2022, Volume and Issue: 27(1)

Published: Jan. 13, 2022

SARS-CoV-2, a novel coronavirus, is the agent responsible for COVID-19 pandemic and major public health concern nowadays. The rapid global spread of this coronavirus leads to an increase in hospitalizations thousands deaths many countries. To date, great efforts have been made worldwide efficient management crisis, but there still no effective specific treatment COVID-19. primary therapies treat disease are antivirals, anti-inflammatories respiratory therapy. In addition, antibody currently active essential part SARS-CoV-2 infection treatment. Ongoing trials proposed different therapeutic options including various drugs, convalescent plasma therapy, monoclonal antibodies, immunoglobulin cell present study summarized current evidence these approaches assess their efficacy safety We tried provide comprehensive information about available potential against support researchers physicians any future progress treating patients.

Language: Английский

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Therapeutic advances in COVID-19

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 19(1), P. 38 - 52

Published: Oct. 17, 2022

Language: Английский

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Hypertension and COVID-19: Current Evidence and Perspectives

High Blood Pressure & Cardiovascular Prevention, Journal Year: 2022, Volume and Issue: 29(2), P. 115 - 123

Published: Feb. 20, 2022

Coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a real challenge for health-care systems worldwide. Male sex, older age and the coexistence of chronic comorbidities have been described as most relevant conditions associated with worse prognosis. Early reports suggested that hypertension might represent risk factor susceptibility to SARS-CoV-2 infection, more course COVID-19 increased COVID-19-related deaths. Nevertheless, independent role remains under debate, since is often other cardiovascular (CV) factors in general population, which may also contribute SARS-Cov-2 infection COVID-19. Moreover, antihypertensive drugs, primarily angiotensin-converting inhibitors (ACEIs) ARBs (angiotensin receptor blockers) development outcome appears controversial. Indeed, preclinical studies using these classes drugs potential upregulation angiotensin-converting-enzyme (ACE2) key binding promoting cell entry organism. Renin–angiotensin system (RAS) blockers potentially upregulate ACE2, hence, it has initially hypothesized agents higher progressive However, several clinical do not support detrimental RAS COVID-19, an intense debate about withdrawal or maintenance therapy ACEi/ARB developed. In this review we will discuss available evidence on development.

Language: Английский

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Angiotensin II Type I Receptor (AT1R): The Gate towards COVID-19-Associated Diseases

Molecules, Journal Year: 2022, Volume and Issue: 27(7), P. 2048 - 2048

Published: March 22, 2022

The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, angiotensin-converting enzyme (ACE2), causes downregulation, which subsequently leads dysregulation renin–angiotensin system (RAS) in favor ACE–angiotensin II (Ang II)–angiotensin type I receptor (AT1R) axis. AT1R has a major role RAS by being involved several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated vasoconstriction, proinflammatory, profibrotic, prooxidative consequences Ang II–AT1R axis activation are accompanied hyperinflammatory state (cytokine storm) an distress (ARDS). AT1R, member G protein-coupled (GPCR) family, modulates deleterious effects through multiple downstream signaling pathways, among MAP kinases (ERK 1/2, JNK, p38MAPK), tyrosine (PDGF, EGFR, insulin receptor), nonreceptor (Src, JAK/STAT, focal adhesion kinase (FAK)), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating symptoms, but because ACE2 expressed various body tissues, extrapulmonary pathologies also manifested, neurologic disorders, vasculature myocardial complications, kidney injury, gastrointestinal hepatic hyperglycemia, dermatologic complications. Therefore, development drugs based on blockers, such as angiotensin blockers (ARBs), that inhibit damaging cascade may become one most promising approaches treatment near future. We herein review general features with special focus receptor-mediated different pathways leading specific responses. In addition, we provide latest insights into roles outcomes systems human body, ARBs tentative pharmacological agents treat COVID-19.

Language: Английский

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Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support–Free Days in Patients Hospitalized With COVID-19

JAMA, Journal Year: 2023, Volume and Issue: 329(14), P. 1183 - 1183

Published: April 11, 2023

Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.

Language: Английский

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Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 145, P. 112420 - 112420

Published: Nov. 12, 2021

Deciphering the molecular downstream consequences of severe acute respiratory syndrome coronavirus (SARS-CoV)- 2 infection is important for a greater understanding disease and treatment planning. Furthermore, underlying mechanisms diagnostic therapeutic strategies can help in development vaccines drugs against COVID-19. At present, SARS-CoV-2 host cells are not sufficiently comprehended. Some proposed considering existing similarities between other members β-CoVs, others explained based on studies advanced structure function SARS-CoV-2. In this review, we endeavored to map possible response following surveyed current research conducted by vitro, vivo human observations, as well suggestions. We addressed specific signaling events that cause cytokine storm demonstrated three forms cell death virus infection, including apoptosis, pyroptosis, necroptosis. Given elicited pathways, introduced pathway-based targets; ADAM17 was especially highlighted one most elements several pathways involved immunopathogenesis also provided drug candidates these targets. Moreover, cytokine-cytokine receptor interaction pathway found cross-talk through pathway-pathway analysis infection.

Language: Английский

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Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 13, 2022

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection has dramatically influenced various aspects the world. It is urgent to thoroughly study pathology and underlying mechanisms for developing effective strategies prevent treat this threatening disease. universally acknowledged that cell death autophagy are essential crucial maintaining host homeostasis participating in pathogenesis. At present, more than twenty different types have been discovered, some parts which fully understood, whereas need investigation. Increasing studies indicated might play an important role virus pathogenicity. However, knowledge interactions related SARS-CoV-2 between lacks systematic elucidation. Therefore, review, we comprehensively delineate how manipulates diverse (including apoptosis, necroptosis, pyroptosis, ferroptosis, NETosis) itself benefits, simultaneously involved occurrence progression COVID-19, aiming provide a reasonable basis existing interventions further development novel therapies.

Language: Английский

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Renin‐Angiotensin System Inhibitors in Patients With COVID‐19: A Meta‐Analysis of Randomized Controlled Trials Led by the International Society of Hypertension

Journal of the American Heart Association, Journal Year: 2022, Volume and Issue: 11(17)

Published: Aug. 24, 2022

Background Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis RASi Methods Results MEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Controlled Trial Register were searched that randomly assigned patients COVID-19 continuation/commencement versus no therapy. The primary outcome was all-cause mortality at ≤30 days. A total 14 met inclusion criteria enrolled 1838 participants (aged 59 years, 58% men, mean follow-up 26 days). Of trials, 11 contributed data. found effect control on (7.2% 7.5%; relative risk [RR], 0.95; [95% CI, 0.69-1.30]) either overall or subgroups defined by severity trial type. Network identified difference between angiotensin-converting enzyme angiotensin II receptor blockers. users had nonsignificant reduction acute myocardial infarction (2.1% 3.6%; RR, 0.59; 0.33-1.06]), but increased kidney injury (7.0% 1.82; 1.05-3.16]), initiated continued RASi. There increase need dialysis differences congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, mechanical ventilation. Conclusions This evaluating inhibitors/angiotensin blockers mortality, borderline decrease infarction, an Our findings provide strong evidence can be used safely

Language: Английский

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The role of cell death in SARS-CoV-2 infection

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 20, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), showing high infectiousness, resulted in an ongoing pandemic termed disease 2019 (COVID-19). COVID-19 cases often experience distress syndrome, which has caused millions of deaths. Apart from triggering inflammatory and immune responses, many viral infections can cause programmed cell death infected cells. Cell mechanisms have a vital role maintaining suitable environment to achieve normal functionality. Nonetheless, these processes are dysregulated, potentially contributing pathogenesis. Over the past decades, multiple pathways becoming better understood. Growing evidence suggests that induction by may significantly contributes infection pathogenicity. However, interaction SARS-CoV-2 with death, together its associated mechanisms, is yet be elucidated. In this review, we summarize existing concerning molecular modulation as well viral-host interactions, shed new light on antiviral therapy against SARS-CoV-2.

Language: Английский

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New insights into the role of Klotho in inflammation and fibrosis: molecular and cellular mechanisms

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 6, 2024

As the body's defense mechanism against damage and infection, inflammatory response is a pathological process that involves range of cells cytokines. A healthy helps body repair by eliminating dangerous irritants. However, tissue fibrosis can result from an overly intense or protracted response. The anti-aging gene Klotho suppresses oxidation, delays aging, fosters development various organs. Numerous investigations conducted in last few years have discovered expression changed variety clinical diseases strongly linked to course outcome disease. functions as co-receptor for FGF humoral factor mediates intracellular signaling pathways such transforming growth β (TGF-β), toll-like receptors (TLRs), nuclear factor-kappaB (NF-κB), renin -angiotensin system (RAS), mitogen-activated protein kinase (MAPK). It also interferes with phenotype function cells, monocytes, macrophages, T B cells. Additionally, it regulates production factors. This article aims examine Klotho's scientific advances terms order provide novel therapy concepts fibrotic disorders.

Language: Английский

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