Repurposing Cardio-Metabolic Drugs to Fight Covid19.
Ontology highlight
ABSTRACT:
SUBMITTER: Battistoni A
PROVIDER: S-EPMC8441229 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The current 2019 novel coronavirus disease (COVID-19), an emerging infectious disease, is undoubtedly the most challenging pandemic in the 21st century. A total of 92,977,768 confirmed cases of COVID-19 and 1,991,289 deaths were reported globally up to January 14, 2021. COVID-19 also affects people's mental health and quality of life. At present, there is no effective therapeutic strategy for the management of this disease. Therefore, in the absence of a specific vaccine or curative treatment, it is an urgent need to identify safe, effective and globally available drugs for reducing COVID-19 morbidity and fatalities. In this review, we focus on selective serotonin reuptake inhibitors (SSRIs: a class of antidepressant drugs with widespread availability and an optimal tolerability profile) that can potentially be repurposed for COVID-19 and are currently being tested in clinical trials. We also summarize the existing literature on what is known about the link between serotonin (5-HT) and the immune system. From the evidence reviewed here, we propose fluoxetine as an adjuvant therapeutic agent for COVID-19 based on its known immunomodulatory, anti-inflammatory and antiviral properties. Fluoxetine may potentially reduce pro-inflammatory chemokine/cytokines levels (such as CCL-2, IL-6, and TNF-α) in COVID-19 patients. Furthermore, fluoxetine may help to attenuate neurological complications of COVID-19.
| S-EPMC7973060 | biostudies-literature
Project description:Currently, there are no treatment options available for the deadly contagious disease, coronavirus disease 2019 (COVID-19). Drug repurposing is a process of identifying new uses for approved or investigational drugs and it is considered as a very effective strategy for drug discovery as it involves less time and cost to find a therapeutic agent in comparison to the de novo drug discovery process. The present review will focus on the repurposing efficacy of the currently used drugs against COVID-19 and their mechanisms of action, pharmacokinetics, dosing, safety, and their future perspective. Relevant articles with experimental studies conducted in-silico, in-vitro, in-vivo, clinical trials in humans, case reports, and news archives were selected for the review. Number of drugs such as remdesivir, favipiravir, ribavirin, lopinavir, ritonavir, darunavir, arbidol, chloroquine, hydroxychloroquine, tocilizumab and interferons have shown inhibitory effects against the SARS-CoV2 in-vitro as well as in clinical conditions. These drugs either act through virus-related targets such as RNA genome, polypeptide packing and uptake pathways or target host-related pathways involving angiotensin-converting enzyme-2 (ACE2) receptors and inflammatory pathways. Using the basic knowledge of viral pathogenesis and pharmacodynamics of drugs as well as using computational tools, many drugs are currently in pipeline to be repurposed. In the current scenario, repositioning of the drugs could be considered the new avenue for the treatment of COVID-19.
| S-EPMC7474498 | biostudies-literature
Project description:Influenza viruses still constitute a real public health problem today. To cope with the emergence of new circulating strains, but also the emergence of resistant strains to classic antivirals, it is necessary to develop new antiviral approaches. This review summarizes the state-of-the-art of current antiviral options against influenza infection, with a particular focus on the recent advances of anti-influenza drug repurposing strategies and their potential therapeutic, regulatory and economic benefits. The review will illustrate the multiple ways to reposition molecules for the treatment of influenza, from adventitious discovery to in silico-based screening. These novel antiviral molecules, many of which targeting the host cell, in combination with conventional antiviral agents targeting the virus, will ideally enter the clinics and reinforce the therapeutic arsenal to combat influenza virus infections.
| S-EPMC6434107 | biostudies-literature
Project description:Cancers are regarded as one of the main causes of death and result in high health burden worldwide. The management of cancer include chemotherapy, surgery and radiotherapy. The chemotherapy, which involves the use of chemical agents with cytotoxic actions is utilised as a single treatment or combined treatment. However, these managements of cancer such as chemotherapy poses some setbacks such as cytotoxicity on normal cells and the problem of anticancer drug resistance. Therefore, the use of other therapeutic agents such as antidiabetic drugs is one of the alternative interventions used in addressing some of the limitations in the use of anticancer agents. Antidiabetic drugs such as sulfonylureas, biguanides and thiazolidinediones showed beneficial and repurposing actions in the management of cancer, thus, the activities of these drugs against cancer is attributed to some of the metabolic links between the two disorders and these includes hyperglycaemia, hyperinsulinemia, inflammation, and oxidative stress as well as obesity. Furthermore, some studies showed that the use of antidiabetic drugs could serve as risk factors for the development of cancerous cells particularly pancreatic cancer. However, the beneficial role of these chemical agents overweighs their detrimental actions in cancer management. Hence, the present review indicates the metabolic links between cancer and diabetes and the mechanistic actions of antidiabetic drugs in the management of cancers.
| S-EPMC8447515 | biostudies-literature
Project description:ObjectiveThere has been a significant increase in the prescribing of medication for chronic non-cancer pain. In a UK population sample, we aimed to assess cardio-metabolic (CM) health in those taking these chronic pain medications.Methods133,401 participants from the UK Biobank cohort were studied. BMI, waist cm and hypertension were compared between those on drugs prescribed for chronic pain and CM drugs to those on CM drugs only. Multiple confounders were controlled for.ResultsThose taking opiates and CM drugs had the worst CM health profile with a 95%, 82% and 63% increased odds of reporting obesity, 'very high risk' waist circumference and hypertension, respectively (OR [95% CI] 1.95 [1.75-2.17], 1.82 [1.63-2.03], 1.63 [1.45-1.84]), compared to those on CM drugs alone. Those taking neuropathic pain medications and CM drugs also demonstrate worse CM profile than those taking CM drugs only.ConclusionsThe impact of medications for chronic pain and sleep upon CM health and obesity is of concern for these classes of drugs which have been recently labelled as dependency forming medications. The results from this cross sectional study warrants further investigation and adds further support to calls for these medications to be prescribed for shorter periods.
| S-EPMC5718411 | biostudies-literature
Project description:Metabolic diseases and diabetes represent an increasing global challenge for human health care. As associated with a strongly elevated risk of developing atherosclerosis, kidney failure and death from myocardial infarction or stroke, the treatment of diabetes requires a more effective approach than lowering blood glucose levels. This review summarizes the evidence for the cardioprotective benefits induced by antidiabetic agents, including sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP1-RA), along with sometimes conversely discussed effects of dipeptidyl peptidase-4 inhibitor (DPP4i) and metformin in patients with high cardiovascular risk with or without type 2 diabetes. Moreover, the proposed mechanisms of the different drugs are described based on the results of preclinical studies. Recent cardiovascular outcome trials unexpectedly confirmed a beneficial effect of GLP-1RA and SGLT2i in type 2 diabetes patients with high cardiovascular risk and with standard care, which was independent of glycaemic control. These results triggered a plethora of studies to clarify the underlying mechanisms and the relevance of these effects. Taken together, the available data strongly highlight the potential of repurposing the original antidiabetics GLP1-RA and SGLT2i to improve cardiovascular outcome even in non-diabetic patients with cardiovascular diseases.
| S-EPMC7522553 | biostudies-literature
Project description:BackgroundMany drugs approved for other indications can control the growth of tumor cells and limit adverse events (AE).Data sourcesLiterature searches with keywords 'repurposing and cancer' books, websites: https://clinicaltrials.gov/, for drug structures: https://pubchem.ncbi.nlm.nih.gov/.Areas of agreementIntroducing approved drugs, such as those developed to treat diabetes (Metformin) or inflammation (Thalidomide), identified to have cytostatic activity, can enhance chemotherapy or even replace more cytotoxic drugs. Also, anti-inflammatory compounds, cytokines and inhibitors of proteolysis can be used to control the side effects of chemo- and immuno-therapies or as second-line treatments for tumors resistant to kinase inhibitors (KI). Drugs specifically developed for cancer therapy, such as interferons (IFN), the tyrosine KI abivertinib TKI (tyrosine kinase inhibitor) and interleukin-6 (IL-6) receptor inhibitors, may help control symptoms of Covid-19.Areas of controversyBetter knowledge of mechanisms of drug activities is essential for repurposing. Chemotherapies induce ER stress and enhance mutation rates and chromosome alterations, leading to resistance that cannot always be related to mutations in the target gene. Metformin, thalidomide and cytokines (IFN, tumor necrosis factor (TNF), interleukin-2 (IL-2) and others) have pleiomorphic activities, some of which can enhance tumorigenesis. The small and fragile patient pools available for clinical trials can cloud the data on the usefulness of cotreatments.Growing pointsBetter understanding of drug metabolism and mechanisms should aid in repurposing drugs for primary, adjuvant and adjunct treatments.Areas timely for developing researchOptimizing drug combinations, reducing cytotoxicity of chemotherapeutics and controlling associated inflammation.
| S-EPMC7929227 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is a complex disorder that has evolved in recent years as the leading global cause of chronic liver damage. The main obstacle to better disease management pertains to the lack of approved pharmacological interventions for the treatment of nonalcoholic steatohepatitis (NASH) and NASH-fibrosis-the severe histological forms. Over the past decade, tremendous advances have been made in NAFLD research, resulting in the discovery of disease mechanisms and novel therapeutic targets. Hence, a large number of pharmacological agents are currently being tested for safety and efficacy. These drugs are in the initial pharmacological phases (phase 1 and 2), which involve testing tolerability, therapeutic action, and pharmacological issues. It is thus reasonable to assume that the next generation of NASH drugs will not be available for clinical use for foreseeable future. The expected delay can be mitigated by drug repurposing or repositioning, which essentially relies on identifying and developing new uses for existing drugs. Here, we propose a drug candidate selection method based on the integration of molecular pathways of disease pathogenesis into network analysis tools that use OMICs data as well as multiples sources, including text mining from the medical literature.
| S-EPMC6478618 | biostudies-literature
Project description:Drug repurposing is a fast and consolidated approach for the research of new active compounds bypassing the long streamline of the drug discovery process. Several drugs in clinical practice have been reported for modulating the major Hippo pathway's terminal effectors, namely YAP (Yes1-associated protein), TAZ (transcriptional co-activator with PDZ-binding motif) and TEAD (transcriptional enhanced associate domains), which are directly involved in the regulation of cell growth and tissue homeostasis. Since this pathway is known to have many cross-talking phenomena with cell signaling pathways, many efforts have been made to understand its importance in oncology. Moreover, this could be relevant to obtain new molecular tools and potential therapeutic assets. In this review, we discuss the main mechanisms of action of the best-known compounds, clinically approved or investigational drugs, able to cross-talk and modulate the Hippo pathway, as an attractive strategy for the discovery of new potential lead compounds.
| S-EPMC6162436 | biostudies-literature
Project description:The Repurposing Drugs in Oncology (ReDO) Project seeks to repurpose well-known and well-characterised non-cancer drugs for new uses in oncology. The rationale for this project is presented, examining current issues in oncological drug development, challenges for health systems, and existing and future patient needs. In addition to discussing the advantages of repurposing, the paper also outlines some of the characteristics used in the selection of drug candidates by this project. Challenges in moving candidate drugs into clinical trial and subsequent practice are also discussed.
| S-EPMC4096030 | biostudies-literature