Imiquimod - A toll like receptor 7 agonist - Is an ideal option for management of COVID 19

Angelopoulou, Athina; Alexandris, Nikos; Konstantinou, Evangelia; Mesiakaris, Konstantinos; Zanidis, Charilaos; Farsalinos, Konstantinos; Poulas, Konstantinos

doi:10.1016/j.envres.2020.109858

Cited by 75 publications

(91 citation statements)

References 71 publications

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“…Various other immune potentiating and immunotherapeutic approaches such as convalescent plasma therapy, 47,[62][63][64] antibodies (neutralizing antibodies, monoclonal antibodies), intravenous immunoglobulins (IVIg); 47,[65][66][67] T cells and Natural killer (NK) cells based immunotherapies, [68][69][70][71] Tolllike receptors (TLRs), 72,73 cytokine therapies, 74 and various immunomodulatory drugs, [75][76][77] have all revealed promising results to safeguard health of COVID-19 patients.…”

mentioning

confidence: 99%

COVID-19 in the elderly people and advances in vaccination approaches

Dhama

Patel

Natesan

et al. 2020

Human Vaccines & Immunotherapeutics

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mentioning

confidence: 99%

COVID-19 in the elderly people and advances in vaccination approaches

Dhama

Patel

Natesan

et al. 2020

Human Vaccines & Immunotherapeutics

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“…Imiquimod acts as an agonist of toll-like receptor 7, which is crucial in recognising single-stranded RNA viruses, such as SARS-CoV-2. Toll-like receptors generate antiviral immunity and act to induce favourable type I interferon response, which in turn induces the expression of interferon-stimulated genes leading to the inhibition of viral replication [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

Network machine learning maps phytochemically rich “Hyperfoods” to fight COVID-19

et al. 2021

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In this paper, we introduce a network machine learning method to identify potential bioactive anti-COVID-19 molecules in foods based on their capacity to target the SARS-CoV-2-host gene-gene (protein-protein) interactome. Our analyses were performed using a supercomputing DreamLab App platform, harnessing the idle computational power of thousands of smartphones. Machine learning models were initially calibrated by demonstrating that the proposed method can predict anti-COVID-19 candidates among experimental and clinically approved drugs (5658 in total) targeting COVID-19 interactomics with the balanced classification accuracy of 80–85% in 5-fold cross-validated settings. This identified the most promising drug candidates that can be potentially “repurposed” against COVID-19 including common drugs used to combat cardiovascular and metabolic disorders, such as simvastatin, atorvastatin and metformin. A database of 7694 bioactive food-based molecules was run through the calibrated machine learning algorithm, which identified 52 biologically active molecules, from varied chemical classes, including flavonoids, terpenoids, coumarins and indoles predicted to target SARS-CoV-2-host interactome networks. This in turn was used to construct a “food map” with the theoretical anti-COVID-19 potential of each ingredient estimated based on the diversity and relative levels of candidate compounds with antiviral properties. We expect this in silico predicted food map to play an important role in future clinical studies of precision nutrition interventions against COVID-19 and other viral diseases.

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“…It should be noted that stimulation of other TLRs in this early window of infection could have similar therapeutic value in immunocompromised patients. Imiquimod, for instance is an activator of TLR7 and has been proposed to enhance the innate and adaptive immunity in early stage COVID-19 patients ( Angelopoulou et al, 2020 ). Also other non-viral specific TLRs such as TLR5 which is activated by bacterial Flagellin has been proposed for vaccine or adjuvant development to generate protective innate immunity against SARS-CoV-2 ( Chakraborty et al, 2020 ).…”

Section: Multifaceted Potential Of Drug Target Tlr9 For Covid-19mentioning

confidence: 99%

“…Control of the cytokine storm by means of immunomodulators, including TLR7 and TLR8 antagonists and inhibitors of cellular mediators downstream of TLRs such as recombinant human IL-6 monoclonal antibody have been proposed and are currently under clinical investigation ( Ye et al, 2020 ; Felsenstein et al, 2020 ; Lythgoe and Middleton, 2020 ; Poulas et al, 2020 ; Patra et al, 2020 ). Moreover, the TLR7 agonist, Imiquimod, is proposed as candidate to manage early stage COVID-19 patients ( Angelopoulou et al, 2020 ). The effectiveness of TLR9 agonists for the use as vaccine adjuvants has also been suggested ( Oberemok et al, 2020 ).In contrast to the available papers that more broadly focus on TLR3, 7 and 8, the here presented work, elaborates specifically on the role of TLR9 in defense against SARS-CoV-2 and introduces the hypothetical positioning of exaggerated TLR9 activation in severe COVID-19 pathology.…”

Section: Introductionmentioning

confidence: 99%

TLR9 and COVID-19: A Multidisciplinary Theory of a Multifaceted Therapeutic Target

Bezemer

Garssen

2021

Front. Pharmacol.

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By mapping the clinical pathophysiology of the novel coronavirus disease 2019 (COVID-19) against insights from virology, immunology, genomics, epidemiology and pharmacology, it is here proposed that the pathogen recognition receptor called toll like receptor 9 (TLR9) might have a pivotal role in the pathogenesis of COVID-19. Severe Acute Respiratory Syndrome Coronavirus 2, is causing the greatest global social and economic disruption since world war II. Lack of a vaccine, lack of successful treatment and limitations of the healthcare workforce and resources needed to safeguard patients with severe COVID-19 on the edge of life, demands radical preventive measures. It is urgently needed to identify biomarkers and drug candidates so that vulnerable individuals can be recognized early and severe multi-organ complications can be prevented or dampened. The TLR9 COVID-19 hypothesis describes a mechanism of action that could explain a wide spectrum of manifestations observed in patients with severe COVID-19. The introduced hypothesis proposes biomarkers for identification of vulnerable individuals and positions TLR9 as a promising multifaceted intervention target for prevention and/or treatment of COVID-19. TLR9 agonists might have value as prophylactic vaccine adjuvants and therapeutic immune stimulators at the early onset of disease. Additionally, in this current manuscript it is proposed for the first time that TLR9 could be considered as a target of “inhibition” aimed to dampen hyperinflammation and thrombotic complications in vulnerable patients that are at risk of developing late stages of COVID-19. The readily availability of TLR9 modulating drug candidates that have reached clinical testing for other disorders could favor a fast track development scenario, an important advantage under the current high unmet medical need circumstances regarding COVID-19.

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Imiquimod - A toll like receptor 7 agonist - Is an ideal option for management of COVID 19

Cited by 75 publications

References 71 publications

COVID-19 in the elderly people and advances in vaccination approaches

COVID-19 in the elderly people and advances in vaccination approaches

Network machine learning maps phytochemically rich “Hyperfoods” to fight COVID-19

TLR9 and COVID-19: A Multidisciplinary Theory of a Multifaceted Therapeutic Target

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