2-deoxy-d-glucose as an adjunct to standard of care in the medical management of COVID-19: a proof-of-concept and dose-ranging randomised phase II clinical trial

BMC Infectious Diseases, Год журнала: 2022, Номер 22(1)

Опубликована: Авг. 4, 2022

At present, no single efficacious therapeutic exists for acute COVID-19 management and a multimodal approach may be necessary. 2-deoxy-D-glucose (2-DG) is metabolic inhibitor that has been shown to limit multiplication of SARS-CoV-2 in-vitro. We evaluated the efficacy safety 2-DG as adjunct standard care in treatment moderate severe patients.We conducted randomized, open-label, phase II, clinical study evaluate efficacy, safety, tolerability administered (SOC). A total 110 patients between ages 18 65 years with were included. Patients randomized receive 63, 90, or 126 mg/kg/day addition SOC only. Times maintaining SpO2 ≥ 94% on room air, discharge, recovery, vital signs normalisation, improvement by 1 2 points WHO progression scale, negative conversion RT-PCR, requirement intensive care, mortality analyzed assess efficacy.Patients treated 90 plus showed better outcomes. Time was significantly shorter mg compared (median 2.5 days vs. 5 days, Hazard ratio [95% confidence interval] = 2.3 [1.14, 4.64], p 0.0201). discharge from isolation ward, normalization group. All three doses well tolerated. Thirty-three (30.3%) reported adverse events mostly (86%) mild.2-DG benefit over alone COVID-19. The promising trends observed current II encouraging confirmatory evaluation larger III trial.CTRI, CTRI/2020/06/025664. Registered 5th June 2020, http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=44369&EncHid=&modid=&compid=%27,%2744369det%27 .

Язык: Английский

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SARS-CoV-2 Nsp6 damages Drosophila heart and mouse cardiomyocytes through MGA/MAX complex-mediated increased glycolysis

Communications Biology, Год журнала: 2022, Номер 5(1)

Опубликована: Сен. 30, 2022

Abstract SARS-CoV-2 infection causes COVID-19, a severe acute respiratory disease associated with cardiovascular complications including long-term outcomes. The presence of virus in cardiac tissue patients COVID-19 suggests this is direct, rather than secondary, effect infection. Here, by expressing individual proteins the Drosophila heart, we demonstrate interaction Nsp6 host MGA/MAX complex (MGA, PCGF6 and TFDP1). Complementing transcriptomic data from fly heart reveal that blocks antagonistic complex, which shifts balance towards MYC/MAX activates glycolysis—with similar findings mouse cardiomyocytes. Further, -induced glycolysis disrupts mitochondrial function, known to increase reactive oxygen species (ROS) failure; could explain COVID-19-associated pathology. Inhibiting pathway 2-deoxy-D-glucose (2DG) treatment attenuates phenotype flies mice. These point as potential pharmacological target for treating failure.

Язык: Английский

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The Antiviral Effects of 2-Deoxy-D-glucose (2-DG), a Dual D-Glucose and D-Mannose Mimetic, against SARS-CoV-2 and Other Highly Pathogenic Viruses

Molecules, Год журнала: 2022, Номер 27(18), С. 5928 - 5928

Опубликована: Сен. 12, 2022

Viral infection almost invariably causes metabolic changes in the infected cell and several types of host cells that respond to infection. Among changes, most prominent is upregulated glycolysis process as main pathway glucose utilization. Glycolysis activation a common mechanism adaptation viral infections, including noroviruses, rhinoviruses, influenza virus, Zika cytomegalovirus, coronaviruses others. Such provide potential targets for therapeutic approaches could reduce impact inhibitors, especially 2-deoxy-D-glucose (2-DG), have been intensively studied antiviral agents. However, 2-DG’s poor pharmacokinetic properties limit its wide clinical application. Herein, we discuss 2-DG novel analogs potent promising drugs with special emphasis on targeted intracellular processes.

Язык: Английский

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Biocompatible epoxysilane substituted polymer-based nano biosensing platform for label-free detection of cancer biomarker SP17 in patient serum samples

International Journal of Biological Macromolecules, Год журнала: 2023, Номер 239, С. 124325 - 124325

Опубликована: Апрель 11, 2023

Язык: Английский

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Potential Anti-SARS-CoV-2 Prodrugs Activated by Phosphorylation and Their Role in the Aged Population

Molecules, Год журнала: 2023, Номер 28(5), С. 2332 - 2332

Опубликована: Март 2, 2023

The COVID-19 pandemic has flared across every part of the globe and affected populations from different age groups differently. People aged 40 to 80 years or older are at an increased risk morbidity mortality due COVID-19. Therefore, there is urgent requirement develop therapeutics decrease disease in population. Over last few years, several prodrugs have demonstrated significant anti-SARS-CoV-2 effects vitro assays, animal models, medical practice. Prodrugs used enhance drug delivery by improving pharmacokinetic parameters, decreasing toxicity, attaining site specificity. This article discusses recently explored such as remdesivir, molnupiravir, favipiravir, 2-deoxy-D-glucose (2-DG) their implications population, well investigating recent clinical trials.

Язык: Английский

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Granular Hemostatic Composite of Alginate, Calcium, and Zinc for Rapid and Effective Management of Post-Traumatic Hemorrhage

ACS Applied Materials & Interfaces, Год журнала: 2024, Номер 16(8), С. 10565 - 10579

Опубликована: Фев. 20, 2024

Post-traumatic hemorrhage, which can result from accidents or battlefield injuries, is a significant global concern due to the high prehospital mortality rate. Substantial efforts have been made develop hemostatic agents that effectively reduce hemorrhage in immediate aftermath of traumatic event. The present study investigated potential efficacy Ca2+ and Zn2+ supplemented sodium alginate-based dry particles (SA-CZ DHP) manage excessive blood loss post-traumatic hemorrhage. SA-CZ DHP were developed, followed by their physical biochemical characterization, cytocompatibility hemocompatibility testing, critical evaluation vitro vivo. safe showed absorption accelerated clotting kinetics with reduced coagulation time (≈70%, p < 0.0001) whole human blood, observed insignificant hemolysis uninterrupted RBC morphology. significantly mean (≈90% SD rats tail incision), bleeding (≈60% BALB/c mice incision) was at par commercially available Celox granules. In conclusion, biocompatible exhibited rapid effective management loss. It also pertinent note developed formulation could be cost-effective alternative its commercial counterparts.

Язык: Английский

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Mechanistic-Based Classification of Endocytosis-Related Inhibitors: Does It Aid in Assigning Drugs against SARS-CoV-2?

Viruses, Год журнала: 2023, Номер 15(5), С. 1040 - 1040

Опубликована: Апрель 23, 2023

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) canonically utilizes clathrin-mediated endocytosis (CME) and several other endocytic mechanisms to invade airway epithelial cells. Endocytic inhibitors, particularly those targeting CME-related proteins, have been identified as promising antiviral drugs. Currently, these inhibitors are ambiguously classified chemical, pharmaceutical, or natural inhibitors. However, their varying may suggest a more realistic classification system. Herein, we present new mechanistic-based of in which they segregated among four distinct classes including: (i) that disrupt endocytosis-related protein-protein interactions, assembly dissociation complexes; (ii) large dynamin GTPase and/or kinase/phosphatase activities associated with endocytosis; (iii) modulate the structure subcellular components, especially plasma membrane, actin; (iv) cause physiological metabolic alterations niche. Excluding drugs designed halt SARS-CoV-2 replication, drugs, either FDA-approved suggested through basic research, could be systematically assigned one classes. We observed many anti-SARS-CoV-2 included class III IV interfere structural integrity respectively. This perspective contribute our understanding relative efficacy support optimization individual combined potential against SARS-CoV-2. selectivity, effects, possible interactions non-endocytic cellular targets need clarification.

Язык: Английский

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Metabolic dysregulation impairs lymphocyte function during severe SARS-CoV-2 infection

Communications Biology, Год журнала: 2023, Номер 6(1)

Опубликована: Апрель 7, 2023

Abstract Cellular metabolic dysregulation is a consequence of SARS-CoV-2 infection that key determinant disease severity. However, how perturbations influence immunological function during COVID-19 remains unclear. Here, using combination high-dimensional flow cytometry, cutting-edge single-cell metabolomics, and re-analysis transcriptomic data, we demonstrate global hypoxia-linked switch from fatty acid oxidation mitochondrial respiration towards anaerobic, glucose-dependent metabolism in CD8 + Tc, NKT, epithelial cells. Consequently, found strong immunometabolism was tied to increased cellular exhaustion, attenuated effector function, impaired memory differentiation. Pharmacological inhibition mitophagy with mdivi-1 reduced excess glucose metabolism, resulting enhanced generation SARS-CoV-2- specific cytokine secretion, augmented cell proliferation. Taken together, our study provides critical insight regarding the mechanisms underlying effect on host immune highlights as promising therapeutic target for treatment.

Язык: Английский

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The potential role of ferroptosis in COVID-19-related cardiovascular injury

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 168, С. 115637 - 115637

Опубликована: Окт. 14, 2023

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a global health threat in 2019. An important feature of the disease is that multiorgan symptoms SARS-CoV-2 infection persist after recovery. Evidence indicates people who recovered from even those under age 65 years without cardiovascular risk factors such smoking, obesity, hypertension, and diabetes, had significantly increased for up to one year diagnosis. Therefore, it closely monitor individuals have COVID-19 potential damage may manifest at later stage. Ferroptosis an iron-dependent form non-apoptotic cell death characterized production reactive oxygen species (ROS) lipid peroxide levels. Several studies demonstrated ferroptosis plays role cancer, ischemia/reperfusion injury (I/RI), other diseases. Altered iron metabolism, upregulation species, glutathione peroxidase 4 inactivation are striking features COVID-19-related injury. can cause ferroptosis, leading damage. Understanding mechanism injuries will contribute development treatment regimens preventing or reducing complications. In this article, we go over pathophysiological underpinnings SARS-CoV-2-induced chronic injury, function prospective approaches.

Язык: Английский

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Surface air gas discharge plasma: An ecofriendly virus inactivation approach to enhance CPRRs mediated antiviral genes expression against airborne bio-contaminant (human Coronavirus-229E)

Environmental Pollution, Год журнала: 2024, Номер 347, С. 123700 - 123700

Опубликована: Март 6, 2024

Язык: Английский

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