Pentoxifylline: A Drug with Antiviral and Anti-Inflammatory Effects to Be Considered in the Treatment of Coronavirus Disease 2019

Ghasemnejad‐Berenji, Morteza; Pashapour, Sarvin; Sadeghpour, Sonia

doi:10.1159/000512234

Cited by 18 publications

(13 citation statements)

References 21 publications

(21 reference statements)

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“…131 Pentoxifylline has also been proposed for the treatment of COVID-19 as a drug with antiviral, anti-inflammatory and bronchodilatory effects. 132 Colchicine recently associated with impact of on mortality in patients with COVID-19 133,134 ; In addition to its anti-inflammatory effect, it may also exhibit an inhibition of TF 135,136 and has a possible antiviral effect. 137…”

Section: Tf Inhibition In Covid-19mentioning

confidence: 99%

Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It

Cañas

Cañas²,

Bautista-Vargas

et al. 2021

Clin Appl Thromb Hemost

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COVID-19 (Coronavirus Disease 2019) is a highly contagious infection and associated with high mortality rates, primarily in elderly; patients with heart failure; high blood pressure; diabetes mellitus; and those who are smokers. These conditions are associated to increase in the level of the pulmonary epithelium expression of angiotensin-converting enzyme 2 (ACE-2), which is a recognized receptor of the S protein of the causative agent SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Severe cases are manifested by parenchymal lung involvement with a significant inflammatory response and the development of microvascular thrombosis. Several factors have been involved in developing this prothrombotic state, including the inflammatory reaction itself with the participation of proinflammatory cytokines, endothelial dysfunction/endotheliitis, the presence of antiphospholipid antibodies, and possibly the tissue factor (TF) overexpression. ARS-Cov-19 ACE-2 down-regulation has been associated with an increase in angiotensin 2 (AT2). The action of proinflammatory cytokines, the increase in AT2 and the presence of antiphospholipid antibodies are known factors for TF activation and overexpression. It is very likely that the overexpression of TF in COVID-19 may be related to the pathogenesis of the disease, hence the importance of knowing the aspects related to this protein and the therapeutic strategies that can be derived. Different therapeutic strategies are being built to curb the expression of TF as a therapeutic target for various prothrombotic events; therefore, analyzing this treatment strategy for COVID-19-associated coagulopathy is rational. Medications such as celecoxib, cyclosporine or colchicine can impact on COVID-19, in addition to its anti-inflammatory effect, through inhibition of TF.

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Section: Tf Inhibition In Covid-19mentioning

confidence: 99%

Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It

Cañas

Cañas²,

Bautista-Vargas

et al. 2021

Clin Appl Thromb Hemost

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“…Protective effects of ERs mediators were also reported in murine models of pulmonary inflammation induced by influenza virus infection (Robinson et al, 2014;Vermillion et al, 2018). Consistently, ER modulators and estrogen hormones such as estradiol have been presently reviewed as beneficial agents for reducing the severity of SARS-CoV-2 infection (Ghasemnejad-Berenji et al, 2020;Suba, 2020;. It has been reported that ERs activation disrupts NF-κB transactivation and inhibits the transcription factors NF-IL6 and subsequently suppresses the expression of IL-6 gene (Liu et al, 2005).…”

Section: Genistein Effect On Estrogen Receptors (Ers)mentioning

confidence: 83%

“…In this regard, a wide range of clinical symptoms from mild forms such as myalgia, cough, and fever to moderate forms such as localized inflammation and pneumonia which require hospitalization could happen(Lechien et al, 2020 ). It should be mentioned that the cytokine storm which is a main pathological sign of COVID‐19 is an unregulated production of inflammatory cytokines inducing destructive inflammation and causing organ failure such as severe cardiovascular, pulmonary, and kidney injuries in SARS‐CoV‐2 infection (Catanzaro et al, 2020 ; Ghasemnejad‐Berenji et al, 2021 ; Robba et al, 2020 ). In addition, oxidative stress, mitochondrial dysfunction, and apoptosis pathways are involved in this multiple organ failure (de Las Heras et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

An overview of possible pivotal mechanisms of Genistein as a potential phytochemical against SARS‐CoV‐2 infection: A hypothesis

Jafari

Esmaeilzadeh

Khezri

et al. 2022

Journal of Food Biochemistry

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The Coronavirus Disease 2019 (COVID‐19) pandemic has been caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It is a global problem that humanity has not yet found a definitive solution for it. In this regard, a global effort has been done to find effective or potential adjuvant therapies in order to fight this infection. Genistein is a small, biologically active phytoestrogen flavonoid that is found in high amounts in soy and plants of the Fabaceae family. This important compound is known due to its anti‐cancer, anti‐inflammatory, and antioxidant effects. Additionally, protective effects of genistein have been reported in different pathological conditions through modulating intracellular pathways such as PI3K, Akt, mTOR, NF‐κB, PPARγ, AMPK, and Nrf2. Scientific evidence suggests that genistein could have a potential role to treat COVID‐19 through its anti‐inflammatory and anti‐oxidant effects. Furthermore, it appears to interfere with intracellular pathways involved in viral entry into the cell. This review provides a basis for further research and development of clinical applications of genistein as a potential alternative therapy to decrease inflammation and oxidative stress in COVID‐19 patients. Practical applications The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the etiological agent for the Coronavirus Disease 2019 (COVID‐19), has brought unprecedented untold hardship to both developing and developed countries. The inflammation, cytokine storm, and oxidative stress have an important role in the pathogenesis of this infection. In this regard, finding plant‐derived compounds with anti‐inflammatory and anti‐oxidative effects would be very beneficial in reducing the mortality induced by this infection. Genistein an isoflavone derived from soy‐rich products possesses versatile biological activities. It has potent anti‐inflammatory and anti‐oxidative and immunomodulatory effects. Furthermore, this compound may prevent viral entry to host cells and reduce SARS‐CoV2‐induced lung injury. Therefore, we suggest further studies on the effects of genistein on SARS‐Cov‐2 infection.

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“…Clinical studies showed that TF pro-coagulant activity declined after combined treatment with a coagulation inhibitor (clopidogrel) and ASA [74] and that a combined treatment with ASA and other antiplatelet-acting drugs reduced TF levels and thrombin generation in patients with angina pectoris [75]. Similarly, TF inhibition has been discussed as a potential therapeutic strategy in COVID-19 patients in several studies [76][77][78]. Our data showed a significant increase in TF expression in the endothelial layer of the chip model after SARS-CoV-2 infection of the epithelial layer.…”

Section: Discussionmentioning

confidence: 99%

D,L-Lysine-Acetylsalicylate + Glycine (LASAG) Reduces SARS-CoV-2 Replication and Shows an Additive Effect with Remdesivir

Jungwirth

Haring

König

et al. 2022

IJMS

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease-19 (COVID-19) is still challenging healthcare systems and societies worldwide. While vaccines are available, therapeutic strategies are developing and need to be adapted to each patient. Many clinical approaches focus on the repurposing of approved therapeutics against other diseases. However, the efficacy of these compounds on viral infection or even harmful secondary effects in the context of SARS-CoV-2 infection are sparsely investigated. Similarly, adverse effects of commonly used therapeutics against lifestyle diseases have not been studied in detail. Using mono cell culture systems and a more complex chip model, we investigated the effects of the acetylsalicylic acid (ASA) salt D,L-lysine-acetylsalicylate + glycine (LASAG) on SARS-CoV-2 infection in vitro. ASA is commonly known as Aspirin® and is one of the most frequently used medications worldwide. Our data indicate an inhibitory effect of LASAG on SARS-CoV-2 replication and SARS-CoV-2-induced expression of pro-inflammatory cytokines and coagulation factors. Remarkably, our data point to an additive effect of the combination of LASAG and the antiviral acting drug remdesivir on SARS-CoV-2 replication in vitro.

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Pentoxifylline: A Drug with Antiviral and Anti-Inflammatory Effects to Be Considered in the Treatment of Coronavirus Disease 2019

Cited by 18 publications

References 21 publications

Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It

Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It

An overview of possible pivotal mechanisms of Genistein as a potential phytochemical against SARS‐CoV‐2 infection: A hypothesis

D,L-Lysine-Acetylsalicylate + Glycine (LASAG) Reduces SARS-CoV-2 Replication and Shows an Additive Effect with Remdesivir

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