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Can pioglitazone be potentially useful therapeutically in treating patients with COVID-19?

ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic disease (COVID-19) that has spread globally causing more than 30,000 deaths. Despite the immense and ongoing global effort, no efficacious drugs to fight this plague have been identified and patients admitted to the intensive care units (ICU), for respiratory distress, are managed mostly by means of supportive care based on oxygen maintenance. Several authors have reported that the prevalence of hypertension, diabetes, cardiovascular and cerebrovascular diseases comorbidities were indeed frequent among patients with COVID-19, which suggests that these conditions are likely to aggravate and complicate the prognosis. What the aforementioned diseases have in common is a latent chronic inflammatory state that may be associated with the alteration of laboratory parameters that are typical of the metabolic syndrome and insulin resistance. In severe COVID-19 patients laboratory markers of inflammation such as C-reactive protein, IL-6, D-dimer, serum ferritin and lactate dehydrogenase are elevated in many patients; assessed since the 4th-6th day of illness onset, such increases seem to be predictive of an adverse prognosis. Our hypothesis is that drugs belonging to the family of thiazolidinediones (TZD) such as pioglitazone or rosiglitazone, approved for treating the condition of insulin resistance and the accompanying inflammation, could ameliorate the prognosis of those COVID-19 patients with diabetes, hypertension and cardiovascular disorders comorbidities. TZD are PPAR? agonists that act on nuclear receptors, thereby triggering certain transcription factors. TZD were widely used for type-2 diabetes in the first decade of this century and although concerns have been raised for possible side effects associated with long-term treatment, their use has been recently revaluated for their anti-inflammatory properties in numerous medical conditions.

SUBMITTER: Carboni E

PROVIDER: S-EPMC7175844 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Can pioglitazone be potentially useful therapeutically in treating patients with COVID-19?

Carboni Elena E Carta Anna R AR Carboni Ezio E

Medical hypotheses 20200422

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic disease (COVID-19) that has spread globally causing more than 30,000 deaths. Despite the immense and ongoing global effort, no efficacious drugs to fight this plague have been identified and patients admitted to the intensive care units (ICU), for respiratory distress, are managed mostly by means of supportive care based on oxygen maintenance. Several authors have reported that the prevalence of hypertension, ...[more]

PMID: 32344313

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Project description:Estrogen-stimulating principles have been demonstrated to relieve postmenopausal syndrome effectively. Gardenia jasminoides Ellis (GJE) is an herbal medicine possessing multiple pharmacological effects on human health with low toxicity. However, the therapeutic effects of GJE on the management of postmenopausal syndrome and its mechanism of action have not been fully elucidated. In this study, network pharmacology-based approaches were employed to examine steroidogenesis under the influence of GJE. In addition, the possibility of toxicity of GJE was ruled out and four probable active compounds were predicted. In parallel, a chromatographic fraction of GJE with estrogen-stimulating effect was identified and nine major compounds were isolated from this active fraction. Among the nine compounds, four of them were identified by network pharmacology, validating the use of network pharmacology to predict active compounds. Then the phenotypic approaches were utilized to verify that rutin, chlorogenic acid (CGA) and geniposidic acid (GA) exerted an estrogen-stimulating effect on ovarian granulosa cells. Furthermore, the results of target-based approaches indicated that rutin, CGA, and GA could up-regulate the FSHR-aromatase pathway in ovarian granulosa cells. The stimulation of estrogen production by rat ovarian granulosa cells under the influence of the three compounds underwent a decline when the follicle-stimulating hormone receptor (FSHR) was blocked by antibodies against the receptor, indicating the involvement of FSHR in the estradiol-stimulating activity of the three compounds. The effects of the three compounds on estrogen biosynthesis- related gene expression level were further confirmed by Western blot assay. Importantly, the MTT results showed that exposure of breast cancer cells to the three compounds resulted in reduction of cell viability, demonstrating the cytotoxicity of the three compounds. Collectively, rutin, chlorogenic acid and geniposidic acid may contribute to the therapeutic potential of GJE for the treatment of postmenopausal syndrome.

Project description:Background and aimsVaccines are the first line of defense against coronavirus disease 2019 (Covid-19). However, the antiviral drugs provide a new tool to fight the Covid-19 pandemic. Here we aimed for a comparative evaluation of authorized drugs for treating Covid-19 patients.MethodsWe searched in PubMed and Google Scholar using keywords and terms such as Covid, SARS-CoV-2, Coronavirus disease 2019, therapeutic management, hospitalized Covid-19 patients, Covid-19 treatment. We also gathered information from reputed newspapers, web portals, and websites. We thoroughly observed, screened, and included the studies relevant to our inclusion criteria. We included only the United States Food and Drug Administration (FDA) authorized drugs for this review.ResultsWe found that molnupiravir and paxlovid are available for oral use, and remdesivir is for only hospitalized patients. Paxlovid is a combination of nirmatrelvir and ritonavir, nirmatrelvir is a protease inhibitor (ritonavir increases the concentration of nirmatrelvir), and the other two (remdesivir and molnupiravir) are nucleoside analog prodrugs. Remdesivir and molnupiravir doses do not need to adjust in renal and hepatic impairment. However, the paxlovid dose adjustment is required for mild to moderate renal or hepatic impaired patients. Also, the drug is not allowed for Covid-19 patients with severe renal or hepatic impairment. Preliminary studies showed oral antiviral drugs significantly reduce hospitalization or death among mild to severe patients. Moreover, the US FDA has approved four monoclonal antibodies for Covid-19 treatment. Studies suggest that these drugs would reduce the risk of hospitalization or severity of symptoms. World Health Organization strongly recommended the use of corticosteroids along with other antiviral drugs for severe or critically hospitalized patients.ConclusionAll authorized drugs are effective in inhibiting viral replication for most SARS-CoV-2 variants. Therefore, along with vaccines, these drugs might potentially aid in fighting the Covid-19 pandemic.

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Can pioglitazone be potentially useful therapeutically in treating patients with COVID-19?

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Can pioglitazone be potentially useful therapeutically in treating patients with COVID-19?

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