Is Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?

Antioxidants, Год журнала: 2021, Номер 10(11), С. 1677 - 1677

Опубликована: Окт. 25, 2021

Even though COVID-19 is mostly well-known for affecting respiratory pathology, it can also result in several extrapulmonary manifestations, leading to multiorgan damage. A recent reported case of SARS-CoV-2 myocarditis with cardiogenic shock showed a signature myocardial and kidney ferroptosis, novel, iron-dependent programmed cell death. The term ferroptosis was coined the last decade describe form death induced by small molecule erastin. As specific inducer erastin inhibits cystine-glutamate antiporter system Xc-, blocking transportation into cytoplasm cystine, precursor glutathione (GSH) exchange glutamate consequent malfunction GPX4. Ferroptosis promoted intracellular iron overload accumulation polyunsaturated fatty acids (PUFA)-derived lipid peroxides. Since depletion GSH, inactivation GPX4, altered metabolism, upregulation PUFA peroxidation reactive oxygen species are peculiar signs COVID-19, there possibility that may trigger cells multiple organs, thus contributing Here, we review molecular mechanisms its possible relationship infection Finally, analyze potential interventions combat and, therefore, reduce

Язык: Английский

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Endothelial Immunity Trained by Coronavirus Infections, DAMP Stimulations and Regulated by Anti-Oxidant NRF2 May Contribute to Inflammations, Myelopoiesis, COVID-19 Cytokine Storms and Thromboembolism

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Июнь 25, 2021

To characterize transcriptomic changes in endothelial cells (ECs) infected by coronaviruses, and stimulated DAMPs, the expressions of 1311 innate immune regulatomic genes (IGs) were examined 28 EC microarray datasets with 7 monocyte as controls. We made following findings: The majority IGs are upregulated first 12 hours post-infection (PI), maintained until 48 PI human microvascular middle east respiratory syndrome-coronavirus (MERS-CoV) (an model for COVID-19). modulated 21 various PAMPs/DAMPs, including LPS, LPC, shear stress, hyperlipidemia oxLDL. Upregulation many such nucleic acid sensors shared between ECs MERS-CoV those PAMPs DAMPs. Human heart mouse aortic express all four types coronavirus receptors ANPEP, CEACAM1, ACE2, DPP4 virus entry facilitator TMPRSS2 (heart EC); most replication-transcription protein complexes expressed HMEC, which contribute to viremia, thromboembolism, cardiovascular comorbidities COVID-19. have novel trained immunity (TI), subsequent inflammation is enhanced. Upregulated proinflammatory cytokines TNFα, IL6, CSF1 CSF3 TI marker IL-32 well metabolic enzymes epigenetic indicate function HMEC MERS-CoV, may drive cytokine storms. demonstrate a promoting myelopoiesis. Mechanistically, ER stress ROS, together decreased mitochondrial OXPHOS complexes, facilitate response TI. Additionally, an increase regulators mitotic catastrophe cell death, apoptosis, ferroptosis, inflammasomes-driven pyroptosis upregulation pro-thrombogenic factors thromboembolism potential. Finally, NRF2-suppressed ROS regulate responses, TI, thrombosis, death. These results provide insights on roles infections COVID-19, diseases (CVD), inflammation, transplantation, autoimmune disease cancers.

Язык: Английский

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Immunomodulatory and Anti-Inflammatory Properties of Selenium-Containing Agents: Their Role in the Regulation of Defense Mechanisms against COVID-19

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(4), С. 2360 - 2360

Опубликована: Фев. 21, 2022

The review presents the latest data on role of selenium-containing agents in regulation diseases immune system. We mainly considered contributions compounds such as sodium selenite, methylseleninic acid, selenomethionine, and methylselenocysteine, well selenoproteins selenium nanoparticles defense mechanisms against various viral infections, including coronavirus infection (COVID-19). A complete description available for each above underlying processes with active participation these agents, their therapeutic pharmacological potential, is presented. main purpose this to systematize information, supplemented by obtained our laboratory, important all processes. In addition, presented information makes it possible understand key differences action compounds, depending chemical physical properties, which obtaining a holistic picture prospects creating drugs based them.

Язык: Английский

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A Systematic Review of the Global Intervention for SARS-CoV-2 Combating: From Drugs Repurposing to Molnupiravir Approval

Drug Design Development and Therapy, Год журнала: 2022, Номер Volume 16, С. 685 - 715

Опубликована: Март 1, 2022

Abstract: The rising outbreak of SARS-CoV-2 continues to unfold all over the world. development novel effective antiviral drugs fight against is a time cost. As result, some specific FDA-approved have already been repurposed and authorized for COVID-19 treatment. used were either or non-antiviral drugs. Accordingly, present review thoroughly focuses on repurposing efficacy these including clinical trials experienced, combination therapies used, methods followed treatment, their future perspective. Therefore, drug was regarded as an avenue Recently, molnupiravir prodrug medication that approved in United Kingdom November 2021 treatment COVID-19. On other hand, PF-07321332 oral developed by Pfizer. For COVID-19, PF-07321332/ritonavir Phase III studies marketed Paxlovid. Herein, we represented almost history combating from recently available anti-SARS-CoV-2 candidates, new hope end current pandemic. Graphical Keywords: SARS-CoV-2, repurposing, trials, molnupiravir, paxlovid

Язык: Английский

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SARS-CoV-2 Inhibits NRF2-Mediated Antioxidant Responses in Airway Epithelial Cells and in the Lung of a Murine Model of Infection

Microbiology Spectrum, Год журнала: 2023, Номер 11(3)

Опубликована: Апрель 6, 2023

The antioxidant defense system plays a major function in protecting the organism against oxidative damage caused by free radicals. COVID-19 patients often present with biochemical characteristics of uncontrolled pro-oxidative responses respiratory tract.

Язык: Английский

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