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1.
Mol Med ; 28(1): 27, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1724403

ABSTRACT

Acute lung injury (ALI) and acute respiratory distress syndrome, which is a more severe form of ALI, are life-threatening clinical syndromes observed in critically ill patients. Treatment methods to alleviate the pathogenesis of ALI have improved to a great extent at present. Although the efficacy of these therapies is limited, their relevance has increased remarkably with the ongoing pandemic caused by the novel coronavirus disease 2019 (COVID-19), which causes severe respiratory distress syndrome. Several studies have demonstrated the preventive and therapeutic effects of molecular hydrogen in the various diseases. The biological effects of molecular hydrogen mainly involve anti-inflammation, antioxidation, and autophagy and cell death modulation. This review focuses on the potential therapeutic effects of molecular hydrogen on ALI and its underlying mechanisms and aims to provide a theoretical basis for the clinical treatment of ALI and COVID-19.


Subject(s)
Acute Lung Injury/drug therapy , COVID-19/drug therapy , Hydrogen/pharmacology , Protective Agents/pharmacology , Acute Lung Injury/physiopathology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Humans , Sepsis/drug therapy , Sepsis/physiopathology
2.
Molecules ; 26(19)2021 Sep 30.
Article in English | MEDLINE | ID: covidwho-1444276

ABSTRACT

Data obtained from several intensive care units around the world have provided substantial evidence of the strong association between impairment of the renal function and in-hospital deaths of critically ill COVID-19 patients, especially those with comorbidities and requiring renal replacement therapy (RRT). Acute kidney injury (AKI) is a common renal disorder of various etiologies characterized by a sudden and sustained decrease of renal function. Studies have shown that 5-46% of COVID-19 patients develop AKI during hospital stay, and the mortality of those patients may reach up to 100% depending on various factors, such as organ failures and RRT requirement. Catechins are natural products that have multiple pharmacological activities, including anti-coronavirus and reno-protective activities against kidney injury induced by nephrotoxic agents, obstructive nephropathies and AKI accompanying metabolic and cardiovascular disorders. Therefore, in this review, we discuss the anti-SARS-CoV-2 and reno-protective effects of catechins from a mechanistic perspective. We believe that catechins may serve as promising therapeutics in COVID-19-associated AKI due to their well-recognized anti-SARS-CoV-2, and antioxidant and anti-inflammatory properties that mediate their reno-protective activities.


Subject(s)
Acute Kidney Injury/etiology , Antiviral Agents/pharmacology , COVID-19/complications , Catechin/pharmacology , Protective Agents/pharmacology , Acute Kidney Injury/drug therapy , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Catechin/chemistry , Catechin/therapeutic use , Humans , Protective Agents/chemistry , Protective Agents/therapeutic use , SARS-CoV-2/drug effects
3.
JCI Insight ; 6(20)2021 10 22.
Article in English | MEDLINE | ID: covidwho-1403154

ABSTRACT

Endothelial dysfunction accompanies the microvascular thrombosis commonly observed in severe COVID-19. Constitutively, the endothelial surface is anticoagulant, a property maintained at least in part via signaling through the Tie2 receptor. During inflammation, the Tie2 antagonist angiopoietin-2 (Angpt-2) is released from endothelial cells and inhibits Tie2, promoting a prothrombotic phenotypic shift. We sought to assess whether severe COVID-19 is associated with procoagulant endothelial dysfunction and alterations in the Tie2/angiopoietin axis. Primary HUVECs treated with plasma from patients with severe COVID-19 upregulated the expression of thromboinflammatory genes, inhibited the expression of antithrombotic genes, and promoted coagulation on the endothelial surface. Pharmacologic activation of Tie2 with the small molecule AKB-9778 reversed the prothrombotic state induced by COVID-19 plasma in primary endothelial cells. Lung autopsies from patients with COVID-19 demonstrated a prothrombotic endothelial signature. Assessment of circulating endothelial markers in a cohort of 98 patients with mild, moderate, or severe COVID-19 revealed endothelial dysfunction indicative of a prothrombotic state. Angpt-2 concentrations rose with increasing disease severity, and the highest levels were associated with worse survival. These data highlight the disruption of Tie2/angiopoietin signaling and procoagulant changes in endothelial cells in severe COVID-19. Our findings provide rationale for current trials of Tie2-activating therapy with AKB-9778 in COVID-19.


Subject(s)
COVID-19/drug therapy , Endothelial Cells/drug effects , Protective Agents/pharmacology , Receptor, TIE-2/metabolism , Adult , Aged , Aged, 80 and over , Angiopoietin-2/metabolism , Aniline Compounds , Female , Gene Expression , Humans , Lung , Male , Middle Aged , Receptor, TIE-2/genetics , SARS-CoV-2 , Signal Transduction , Sulfonic Acids , Vascular Diseases/metabolism , Young Adult
4.
Oxid Med Cell Longev ; 2021: 7866992, 2021.
Article in English | MEDLINE | ID: covidwho-1403126

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is posing a great threat to the global economy and public health security. Together with the acknowledged angiotensin-converting enzyme 2, glucose-regulated protein 78, transferrin receptor, AXL, kidney injury molecule-1, and neuropilin 1 are also identified as potential receptors to mediate SARS-CoV-2 infection. Therefore, how to inhibit or delay the binding of SARS-CoV-2 with the abovementioned receptors is a key step for the prevention and treatment of COVID-19. As the third gasotransmitter, hydrogen sulfide (H2S) plays an important role in many physiological and pathophysiological processes. Recently, survivors were reported to have significantly higher H2S levels in COVID-19 patients, and mortality was significantly greater among patients with decreased H2S levels. Considering that the beneficial role of H2S against COVID-19 and COVID-19-induced comorbidities and multiorgan damage has been well-examined and reported in some excellent reviews, this review will discuss the recent findings on the potential receptors of SARS-CoV-2 and how H2S modulates the above receptors, in turn blocking SARS-CoV-2 entry into host cells.


Subject(s)
Antiviral Agents/pharmacology , Hydrogen Sulfide/pharmacology , Receptors, Cell Surface/metabolism , SARS-CoV-2/metabolism , Animals , Humans , Organ Specificity/drug effects , Protective Agents/pharmacology , SARS-CoV-2/drug effects
5.
Oxid Med Cell Longev ; 2021: 9919466, 2021.
Article in English | MEDLINE | ID: covidwho-1358940

ABSTRACT

Thrombus is considered to be the pathological source of morbidity and mortality of cardiovascular disease and thrombotic complications, while oxidative stress is regarded as an important factor in vascular endothelial injury and thrombus formation. Therefore, antioxidative stress and maintaining the normal function of vascular endothelial cells are greatly significant in regulating vascular tension and maintaining a nonthrombotic environment. Leonurine (LEO) is a unique alkaloid isolated from Leonurus japonicus Houtt (a traditional Chinese medicine (TCM)), which has shown a good effect on promoting blood circulation and removing blood stasis. In this study, we explored the protective effect and action mechanism of LEO on human umbilical vein endothelial cells (HUVECs) after damage by hydrogen peroxide (H2O2). The protective effects of LEO on H2O2-induced HUVECs were determined by measuring the cell viability, cell migration, tube formation, and oxidative biomarkers. The underlying mechanism of antioxidation of LEO was investigated by RT-qPCR and western blotting. Our results showed that LEO treatment promoted cell viability; remarkably downregulated the intracellular generation of reactive oxygen species (ROS), malondialdehyde (MDA) production, and lactate dehydrogenase (LDH); and upregulated the nitric oxide (NO) and superoxide dismutase (SOD) activity in H2O2-induced HUVECs. At the same time, LEO treatment significantly promoted the phosphorylation level of angiogenic protein PI3K, Akt, and eNOS and the expression level of survival factor Bcl2 and decreased the expression level of death factor Bax and caspase3. In conclusion, our findings suggested that LEO can ameliorate the oxidative stress damage and insufficient angiogenesis of HUVECs induced by H2O2 through activating the PI3K/Akt-eNOS signaling pathway.


Subject(s)
Gallic Acid/analogs & derivatives , Oxidative Stress/drug effects , Signal Transduction/drug effects , Cell Movement/drug effects , Cell Survival/drug effects , Gallic Acid/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , Hydrogen Peroxide/pharmacology , Malondialdehyde/metabolism , Medicine, Chinese Traditional , Neovascularization, Physiologic/drug effects , Nitric Oxide Synthase Type III/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Protective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism
6.
Biomed Pharmacother ; 142: 111957, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1330662

ABSTRACT

The outbreak of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, in December 2019, and its global dissemination became the coronavirus disease 2019 (COVID-19) pandemic declared by the World Health Organization (WHO) on 11 March 2020. In patients undergoing immunotherapy, the effect and path of viral infection remain uncertain. In addition, viral-infected mice and humans show T-cell exhaustion, which is identified after infection with SARS-CoV-2. Notably, they regain their T-cell competence and effectively prevent viral infection when treated with anti-PD-1 antibodies. Four clinical trials are officially open to evaluate anti-PD-1 antibody administration's effectiveness for cancer and non-cancer individuals influenced by COVID-19 based on these findings. The findings may demonstrate the hypothesis that a winning strategy to combat SARS-CoV-2 infection could be the restoration of exhausted T-cells. In this review, we outline the potential protective function of the anti-PD-1 blockade against SARS-CoV-2 infection with the aim to develop SARS-CoV-2 therapy.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antiviral Agents/immunology , COVID-19/drug therapy , COVID-19/immunology , Humans , Immune Checkpoint Inhibitors/immunology , Immune Checkpoint Inhibitors/pharmacology , Immunotherapy/methods , Mice , Protective Agents/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , T-Lymphocytes/immunology
7.
Cell ; 184(9): 2316-2331.e15, 2021 04 29.
Article in English | MEDLINE | ID: covidwho-1135277

ABSTRACT

Most human monoclonal antibodies (mAbs) neutralizing SARS-CoV-2 recognize the spike (S) protein receptor-binding domain and block virus interactions with the cellular receptor angiotensin-converting enzyme 2. We describe a panel of human mAbs binding to diverse epitopes on the N-terminal domain (NTD) of S protein from SARS-CoV-2 convalescent donors and found a minority of these possessed neutralizing activity. Two mAbs (COV2-2676 and COV2-2489) inhibited infection of authentic SARS-CoV-2 and recombinant VSV/SARS-CoV-2 viruses. We mapped their binding epitopes by alanine-scanning mutagenesis and selection of functional SARS-CoV-2 S neutralization escape variants. Mechanistic studies showed that these antibodies neutralize in part by inhibiting a post-attachment step in the infection cycle. COV2-2676 and COV2-2489 offered protection either as prophylaxis or therapy, and Fc effector functions were required for optimal protection. Thus, natural infection induces a subset of potent NTD-specific mAbs that leverage neutralizing and Fc-mediated activities to protect against SARS-CoV-2 infection using multiple functional attributes.


Subject(s)
Antibodies, Monoclonal/pharmacology , Antibodies, Neutralizing/pharmacology , Protective Agents/pharmacology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Animals , Binding, Competitive , COVID-19/immunology , COVID-19/virology , Chemokines/metabolism , Chlorocebus aethiops , HEK293 Cells , Humans , Immunoglobulin Fab Fragments/metabolism , Immunoglobulin G/metabolism , Lung/metabolism , Mice, Inbred C57BL , Models, Molecular , Mutagenesis/genetics , Neutralization Tests , Protein Domains , Vero Cells
8.
Clin Obes ; 11(2): e12439, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1015529

ABSTRACT

The aim of the present manuscript is to discuss on potential pros and cons of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as glucose-lowering agents during COVID-19 pandemic, and what is more to evaluate them as potential candidates for the treatment of patients, affected by COVID-19 infection, with or even without diabetes mellitus type 2. Besides being important glucose-lowering agents, GLP-1RAs pose promising anti-inflammatory and anti-obesogenic properties, pulmonary protective effects, as well as beneficial impact on gut microbiome composition. Hence, taking everything previously mentioned into consideration, GLP-1RAs seem to be potential candidates for the treatment of patients, affected by COVID-19 infection, with or even without type 2 diabetes mellitus, as well as excellent antidiabetic (glucose-lowering) agents during COVID-19 pandemic times.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/pharmacology , Obesity , COVID-19/drug therapy , COVID-19/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Drug Repositioning/methods , Humans , Obesity/drug therapy , Obesity/metabolism , Protective Agents/pharmacology , SARS-CoV-2
9.
Molecules ; 25(23)2020 Dec 07.
Article in English | MEDLINE | ID: covidwho-966360

ABSTRACT

The inflammatory mediator and oxidant agent storm caused by the SARS-CoV-2 infection has been strongly associated with the failure of vital organs observed in critically ill patients with coronavirus disease 2019 (COVID-19) and the death of thousands of infected people around the world. Acute kidney injury (AKI) is a common renal disorder characterized by a sudden and sustained decrease in renal function with a critical influence on poor prognosis and lethal clinical outcomes of various etiologies, including some viral infection diseases. It is known that oxidative stress and inflammation play key roles in the pathogenesis and development of AKI. Quercetin is a natural substance that has multiple pharmacological properties, such as anti-inflammatory action, and is used as a dietary supplement. There is evidence of the anti-coronavirus activities of this compound, including against the target SARS-CoV-2 3CLpro. The ability to inhibit coronavirus and its inflammatory processes is strongly desired in a new drug for the treatment of COVID-19. Therefore, in this review, the dual effect of quercetin is discussed from a mechanistic perspective in relation to AKI kidney injury and its nephroprotective potential to SARS-CoV-2 patients.


Subject(s)
Acute Kidney Injury/drug therapy , COVID-19/complications , Quercetin/pharmacology , Acute Kidney Injury/etiology , Animals , COVID-19/drug therapy , COVID-19/epidemiology , Humans , Morbidity , Protective Agents/pharmacology , Protective Agents/therapeutic use , Quercetin/therapeutic use
10.
Oxid Med Cell Longev ; 2020: 8384742, 2020.
Article in English | MEDLINE | ID: covidwho-788248

ABSTRACT

H2 has shown anti-inflammatory and antioxidant ability in many clinical trials, and its application is recommended in the latest Chinese novel coronavirus pneumonia (NCP) treatment guidelines. Clinical experiments have revealed the surprising finding that H2 gas may protect the lungs and extrapulmonary organs from pathological stimuli in NCP patients. The potential mechanisms underlying the action of H2 gas are not clear. H2 gas may regulate the anti-inflammatory and antioxidant activity, mitochondrial energy metabolism, endoplasmic reticulum stress, the immune system, and cell death (apoptosis, autophagy, pyroptosis, ferroptosis, and circadian clock, among others) and has therapeutic potential for many systemic diseases. This paper reviews the basic research and the latest clinical applications of H2 gas in multiorgan system diseases to establish strategies for the clinical treatment for various diseases.


Subject(s)
Hydrogen/administration & dosage , Hydrogen/pharmacology , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Betacoronavirus , COVID-19 , Coronavirus Infections/therapy , Energy Metabolism/drug effects , Humans , Oxidative Stress/drug effects , Pandemics , Pneumonia, Viral/therapy , Protective Agents/pharmacology , SARS-CoV-2
12.
Nitric Oxide ; 103: 1-3, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-611235

ABSTRACT

It has long been suggested that NO may inhibit an early stage in viral replication. Furthermore, in vitro tests have shown that NO inhibits the replication cycle of severe acute respiratory syndrome coronavirus. Despite smoking being listed as a risk factor to contract Covid-19, only a low proportion of the smokers suffered from SARS-corona infection in China 2003, and from Covid-19 in China, Europe and the US. We hypothesize, that the intermittent bursts of high NO concentration in cigarette smoke may be a mechanism in protecting against the virus. Mainstream smoke from cigarettes contains NO at peak concentrations of between about 250 ppm and 1350 ppm in each puff as compared to medicinal use of no more than 80 to a maximum of 160 ppm. The diffusion of NO through the cell wall to reach the virus should be significantly more effective at the very high NO concentration in the smoke, according to classic laws of physics. The only oxide of nitrogen in the mainstream smoke is NO, and the NO2 concentration that is inhaled is very low or undetectable, and methemoglobin levels are lower in smokers than non-smokers, reasonably explained by the breaths of air in between the puffs that wash out the NO. Specialized iNO machines can now be developed to provide the drug intermittently in short bursts at high concentration dose, which would then provide both a preventative drug for those at high risk, as well as an effective treatment, without the health hazards associated with smoking.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/prevention & control , Nitric Oxide/pharmacology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Protective Agents/pharmacology , Administration, Inhalation , COVID-19 , Coronavirus Infections/drug therapy , Female , Humans , Male , Nitric Oxide/administration & dosage , Protective Agents/administration & dosage , SARS-CoV-2 , Smokers , Smoking
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