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2.
Med Sci Monit ; 28: e934102, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1651076

ABSTRACT

BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action needs further study. This study aimed to explore the anti-coronavirus basis and mechanism of HDHs. MATERIAL AND METHODS Database mining was performed on 7 HDHs. Core ingredients and targets were screened according to ADME rules combined with Neighborhood, Co-occurrence, Co-expression, and other algorithms. GO enrichment and KEGG pathway analyses were performed using the R language. Finally, high-throughput molecular docking was used for verification. RESULTS HDHs mainly acts on NOS3, EGFR, IL-6, MAPK8, PTGS2, MAPK14, NFKB1, and CASP3 through quercetin, luteolin, wogonin, indirubin alkaloids, ß-sitosterol, and isolariciresinol. These targets are mainly involved in the regulation of biological processes such as inflammation, activation of MAPK activity, and positive regulation of NF-kappaB transcription factor activity. Pathway analysis further revealed that the pathways regulated by these targets mainly include: signaling pathways related to viral and bacterial infections such as tuberculosis, influenza A, Ras signaling pathways; inflammation-related pathways such as the TLR, TNF, MAPK, and HIF-1 signaling pathways; and immune-related pathways such as NOD receptor signaling pathways. These pathways play a synergistic role in inhibiting lung inflammation and regulating immunity and antiviral activity. CONCLUSIONS HDHs play a role in the treatment of coronavirus infection by regulating the body's immunity, fighting inflammation, and antiviral activities, suggesting a molecular basis and new strategies for the treatment of COVID-19 and a foundation for the screening of new antiviral drugs.


Subject(s)
COVID-19/drug therapy , Coronavirus/drug effects , Drugs, Chinese Herbal/pharmacology , SARS-CoV-2/drug effects , Alkaloids/chemistry , Alkaloids/pharmacology , Caspase 3/drug effects , Caspase 3/genetics , Coronavirus/metabolism , Coronavirus Infections/drug therapy , Cyclooxygenase 2/drug effects , Cyclooxygenase 2/genetics , Databases, Pharmaceutical , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Flavanones/chemistry , Flavanones/pharmacology , Humans , Indoles/chemistry , Indoles/pharmacology , Interleukin-6/genetics , Lignin/chemistry , Lignin/pharmacology , Luteolin/chemistry , Luteolin/pharmacology , Mitogen-Activated Protein Kinase 14/drug effects , Mitogen-Activated Protein Kinase 14/genetics , Mitogen-Activated Protein Kinase 8/drug effects , Mitogen-Activated Protein Kinase 8/genetics , Molecular Docking Simulation , NF-kappa B p50 Subunit/drug effects , NF-kappa B p50 Subunit/genetics , Naphthols/chemistry , Naphthols/pharmacology , Nitric Oxide Synthase Type III/drug effects , Nitric Oxide Synthase Type III/genetics , Protein Interaction Maps , Quercetin/chemistry , Quercetin/pharmacology , SARS-CoV-2/metabolism , Signal Transduction , Sitosterols/chemistry , Sitosterols/pharmacology , Transcriptome/drug effects , Transcriptome/genetics
3.
Pathog Glob Health ; 116(3): 178-184, 2022 05.
Article in English | MEDLINE | ID: covidwho-1437790

ABSTRACT

For COVID-19 (Coronavirus Disease-2019) cases, detecting host-based factors that predispose to infection is a very important research area. In this study, the aim is to investigate the MBL2 and NOS3 gene polymorphisms in COVID-19 patients with lung involvement, whose first nasopharyngeal PCR results were negative. Seventy-nine patients diagnosed with COVID-19 between April-June 2020 who were admitted to a university hospital, and 100 healthy controls were included. In the first statistical analysis performed between PCR-positive, CT-negative and PCR-negative, CT-positive patients; the AB of MBL2 genotype was significantly higher in the first group (p = 0.049). The B allele was also significantly higher in the same subgroup (p = 0.001). The absence of the AB genotype was found to increase the risk of CT positivity by 6.9 times. The AB genotype of MBL2 was higher in healthy controls (p = 0.006). The absence of the AB genotype was found to increase the risk of CT positivity; also, it can be used for early detection and isolation of patients with typical lung involvement who had enough viral loads, but whose initial PCR results were negative.


Subject(s)
COVID-19 , Mannose-Binding Lectin , COVID-19/diagnosis , Genetic Predisposition to Disease , Genotype , Humans , Mannose-Binding Lectin/genetics , Nitric Oxide Synthase Type III/genetics , Polymerase Chain Reaction/methods
4.
Nitric Oxide ; 111-112: 64-71, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1164254

ABSTRACT

Symptoms of COVID-19 range from asymptomatic/mild symptoms to severe illness and death, consequence of an excessive inflammatory process triggered by SARS-CoV-2 infection. The diffuse inflammation leads to endothelium dysfunction in pulmonary blood vessels, uncoupling eNOS activity, lowering NO production, causing pulmonary physiological alterations and coagulopathy. On the other hand, iNOS activity is increased, which may be advantageous for host defense, once NO plays antiviral effects. However, overproduction of NO may be deleterious, generating a pro-inflammatory effect. In this review, we discussed the role of endogenous NO as a protective or deleterious agent of the respiratory and vascular systems, the most affected in COVID-19 patients, focusing on eNOS and iNOS roles. We also reviewed the currently available NO therapies and pointed out possible alternative treatments targeting NO metabolism, which could help mitigate health crises in the present and future CoV's spillovers.


Subject(s)
COVID-19/metabolism , Nitric Oxide Synthase Type III/metabolism , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide/metabolism , SARS-CoV-2 , Blood Vessels/metabolism , Gene Expression Regulation, Enzymologic , Humans , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type III/genetics , Respiratory System/metabolism
5.
Ageing Res Rev ; 64: 101201, 2020 12.
Article in English | MEDLINE | ID: covidwho-907102

ABSTRACT

The COVID-19 pandemic poses an imminent threat to humanity, especially to the elderly. The molecular mechanisms underpinning the age-dependent disparity for disease progression is not clear. COVID-19 is both a respiratory and a vascular disease in severe patients. The damage endothelial system provides a good explanation for the various complications seen in COVID-19 patients. These observations lead us to suspect that endothelial cells are a barrier that must be breached before progression to severe disease. Endothelial intracellular defences are largely dependent of the activation of the interferon (IFN) system. Nevertheless, low type I and III IFNs are generally observed in COVID-19 patients suggesting that other intracellular viral defence systems are also activated to protect the young. Intriguingly, Nitric oxide (NO), which is the main intracellular antiviral defence, has been shown to inhibit a wide array of viruses, including SARS-CoV-1. Additionally, the increased risk of death with diseases that have underlying endothelial dysfunction suggest that endothelial NOS-derived nitric oxide could be the main defence mechanism. NO decreases dramatically in the elderly, the hyperglycaemic and the patients with low levels of vitamin D. However, eNOS derived NO occurs at low levels, unless it is during inflammation and co-stimulated by bradykinin. Regrettably, the bradykinin-induced vasodilation also progressively declines with age, thereby decreasing anti-viral NO production as well. Intriguingly, the inverse correlation between the percentage of WT eNOS haplotype and death per 100K population could potentially explain the disparity of COVID-19 mortality between Asian and non-Asian countries. These changes with age, low bradykinin and NO, may be the fundamental reasons that intracellular innate immunity declines with age leading to more severe COVID-19 complications.


Subject(s)
Aging/metabolism , COVID-19/metabolism , COVID-19/mortality , Nitric Oxide Synthase Type III/metabolism , Nitric Oxide/metabolism , Age Factors , Bradykinin , COVID-19/enzymology , COVID-19/genetics , Endothelial Cells/metabolism , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Haplotypes , Humans , Immunity, Innate , Nitric Oxide Synthase Type III/genetics , SARS-CoV-2/pathogenicity
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