Interferon and Toll-Like Receptor 7 Response in COVID-19: Implications of Topical Imiquimod for Prophylaxis and Treatment

Szeto, Mindy D; Maghfour, Jalal; Sivesind, Torunn; Anderson, Jarett; Olayinka, J.; Mamo, Andrina; Runion, Taylor M; Dellavalle, Robert P.

doi:10.1159/000518471

Cited by 8 publications

(7 citation statements)

References 59 publications

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“…After endocytosis of SRS-Cov-2 to the type II pneumocytes of the lungs, viral nucleotides are transported into endosomes where TLR3 and TLR7 are present. Through slightly different pathways, TLR3 and TLR7 activate NF-κB signaling, which results in the production of type I IFNs and proinflammatory cytokines IL-6, TNF-α, and IFN-γ [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study

Alseoudy¹,

Elgamal²,

Abdelghany³

et al. 2022

Clinical Immunology

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Toll-like receptor 3 (TLR3) and TLR7 genes are involved in the host immune response against viral infections including SARS-COV-2. This study aimed to investigate the association between the TLR3(rs3775290) and TLR7(rs179008) polymorphisms with the prognosis and susceptibility to COVID-19 pneumonia accompanying SARS-COV-2 infection. This case-control study included 236 individuals: 136 COVID-19 pneumonia patients and 100 age and sex-matched controls. Two polymorphisms (TLR3 rs3775290 and TLR7 rs179008) were genotyped by allelic discrimination through TaqMan real-time PCR. This study also investigated predictors of mortality in COVID-19 pneumonia through logistic regression. The mutant ‘T/T' genotypes and the ‘T' alleles of TLR3(rs3775290) and TLR7(rs179008) polymorphisms were significantly associated with increased risk of COVID-19 pneumonia. This study did not report association between the mutant ‘T/T' genotypes of TLR3(rs3775290) and TLR7(rs179008) and the disease outcome. In multivariate analysis, the independent predictors of mortality in COVID-19 pneumonia were male sex, SPO2 ≤ 82%, INR > 1, LDH ≥ 1000 U/L, and lymphocyte count<900/mm3 ( P < 0.05).

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Section: Discussionmentioning

confidence: 99%

Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study

Alseoudy¹,

Elgamal²,

Abdelghany³

et al. 2022

Clinical Immunology

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“…[43,44] Therefore, TLRs may be potential targets for manufacturing SARS-CoV-2 vaccines and targeted drugs. [45] To validate the KEGG enrichment results, we molecularly docked the core targets in the above 5 signaling pathways with the corresponding Chinese herbal active ingredients. [46] Molecular docking showed that (2S…”

Section: Discussionmentioning

confidence: 99%

Exploration of Fuzheng Yugan Mixture on COVID-19 based on network pharmacology and molecular docking

Jiang

Zhou

et al. 2023

Medicine

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After the World Health Organization declared coronavirus disease 2019 , as a global pandemic, global health workers have been facing an unprecedented and severe challenge. Currently, a mixturetion to inhibit the exacerbation of pulmonary inflammation caused by COVID-19, Fuzheng Yugan Mixture (FZYGM), has been approved for medical institution mixturetion notification. However, the mechanism of FZYGM remains poorly defined. This study aimed to elucidate the molecular and related physiological pathways of FZYGM as a potential therapeutic agent for COVID-19. Active molecules of FZYGM were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), while potential target genes of COVID-19 were identified by DrugBank and GeneCards. Compound-target networks and protein-protein interactions (PPI) were established by Cytoscape_v3.8.2 and String databases, respectively. The gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Finally, a more in-depth study was performed using molecular docking. Our study identified 7 active compounds and 3 corresponding core targets. The main potentially acting signaling pathways include the interleukin (IL)-17 signaling pathway, tumor necrosis factor (TNF) signaling pathway, Toll-like receptor signaling pathway, Th17 cell differentiation, and coronavirus disease-COVID-19. This study shows that FZYGM can exhibit anti-COVID-19 effects through multiple targets and pathways. Therefore, FZYGM can be considered a drug candidate for the treatment of COVID-19, and it provides good theoretical support for subsequent experiments and clinical applications of COVID-19. Abbreviations: BP = biological processes, CC = cell composition, COVID-19 = coronavirus disease 2019, FZYGM = Fuzheng Yugan Mixture, GO = gene ontology, IL = interleukin, KEGG = Kyoto encyclopedia of genes and genomes, MAPKs = mitogenactivated protein kinases, NF-κB = transcription factor family nuclear factor kappa-B, PPI = protein-protein interaction, TCMSP = traditional Chinese medicine systems pharmacology database and analysis platform, TCM = traditional Chinese medicine, TNF = tumor necrosis factor, TLR = toll-like receptor.

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“…TLRs are a family comprised of 11 transmembrane proteins, which are crucial components in the initiation of innate immune responses ( Szeto et al., 2021 ). TLRs recognize pathogen-associated molecular patterns and trigger the production of pro-inflammatory cytokines as well as type I and II interferons system.…”

Section: Genetic Variations Associated With Severity Of Covid-19mentioning

confidence: 99%

“…Since the production of IFN is mediated via the TLR7 signaling pathway, therapies that directly stimulate endogenous TLR7 could have potential therapeutic benefit for the prevention and treatment of severe COVID-19 infection ( Szeto et al., 2021 ). In addition, genetic variations in TLR7 that located on the X chromosome, may be a possible explanation of the sex biases in COVID-19 severity.…”

Section: Genetic Variations Associated With Severity Of Covid-19mentioning

confidence: 99%

Human genetic basis of severe or critical illness in COVID-19

Chen

et al. 2022

Front. Cell. Infect. Microbiol.

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Coronavirus Disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to considerable morbidity and mortality worldwide. The clinical manifestation of COVID-19 ranges from asymptomatic or mild infection to severe or critical illness, such as respiratory failure, multi-organ dysfunction or even death. Large-scale genetic association studies have indicated that genetic variations affecting SARS-CoV-2 receptors (angiotensin-converting enzymes, transmembrane serine protease-2) and immune components (Interferons, Interleukins, Toll-like receptors and Human leukocyte antigen) are critical host determinants related to the severity of COVID-19. Genetic background, such as 3p21.31 and 9q34.2 loci were also identified to influence outcomes of COVID-19. In this review, we aimed to summarize the current literature focusing on human genetic factors that may contribute to the observed diversified severity of COVID-19. Enhanced understanding of host genetic factors and viral interactions of SARS-CoV-2 could provide scientific bases for personalized preventive measures and precision medicine strategies.

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Interferon and Toll-Like Receptor 7 Response in COVID-19: Implications of Topical Imiquimod for Prophylaxis and Treatment

Cited by 8 publications

References 59 publications

Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study

Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study

Exploration of Fuzheng Yugan Mixture on COVID-19 based on network pharmacology and molecular docking

Human genetic basis of severe or critical illness in COVID-19

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