Challenges in Repurposing Drugs in COVID-19 Pandemic. Debating on Potential New Refinements.
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ABSTRACT:
SUBMITTER: Frega G
PROVIDER: S-EPMC7655924 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Challenges in Repurposing Drugs in COVID-19 Pandemic. Debating on Potential New Refinements.
Frega Giorgio G Palloni Andrea A Di Pasquale Giuseppe G Saccoccio Gioconda G Rizzo Alessandro A Poluzzi Elisabetta E Iannone Primiano P Brandi Giovanni G
Frontiers in pharmacology 20201028
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Project description:The coronavirus disease (COVID-19) pandemic has affected an estimated 16 million persons and caused 0.6 million deaths worldwide by September 2020. The pandemic has led to a rush to repurpose existing drugs, although the underlying evidence base is of variable quality. The improving knowledge of the virology and clinical presentation of COVID-19 is leading to a broadening pool of potential pharmacological targets. The aim of this review is to describe regulatory and pharmacological aspects of drug repurposing and to identify drugs proposed for repurposing in COVID-19 based on registered clinical trials, discussing the evidence to support their use in the treatment of this disease. The challenges of the correct interpretation of existing pre-clinical/clinical evidence as well as the generation of new evidence concerning drug repurposing in COVID-19 will also be discussed. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04321174, NCT04342663, NCT04280705, NCT04244591, NCT04359329, NCT04348695, NCT04304313, NCT043505931.
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Project description:As the COVID-19 is still growing throughout the globe, a thorough investigation into the specific immunopathology of SARS-CoV-2, its interaction with the host immune system and pathogen evasion mechanism may provide a clear picture of how the pathogen can breach the host immune defenses in elderly patients and patients with comorbid conditions. Such studies will also reveal the underlying mechanism of how children and young patients can withstand the disease better. The study of the immune defense mechanisms and the prolonged immune memory from patients population with convalescent plasma may help in designing a suitable vaccine candidate not only for the current outbreak but also for similar outbreaks in the future. The vital drug candidates, which are being tested as potential vaccines or therapeutics against COVID-19, include live attenuated vaccine, inactivated or killed vaccine, subunit vaccine, antibodies, interferon treatment, repurposing existing drugs, and nucleic acid-based vaccines. Several organizations around the world have fast-tracked the development of a COVID-19 vaccine, and some drugs already went to phase III of clinical trials. Hence, here, we have tried to take a quick glimpse of the development stages of vaccines or therapeutic approaches to treat this deadly disease.
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Project description:Novel coronavirus first appeared in Wuhan, China, in December 2019, and it speedily expanded globally. Some medications which are used to treat other diseases seem to be effective in treating COVID-19 even without explicit support. The existing drugs that are summarized in this review primarily focused on therapeutic agents that possessed activity against other RNA viruses such as MERS-CoV and SARS-CoV. Drug repurposing or repositioning is a promising field in drug discovery that identifies new therapeutic opportunities for existing drugs such as corticosteroids, RNA-dependent RNA polymerase inhibitors, interferons, protease inhibitors, ivermectin, melatonin, teicoplanin, and some others. A search for new drug/drug targets is underway. Thus, blocking coronavirus structural protein, targeting viral enzyme, dipeptidyl peptidase 4, and membrane fusion blocker (angiotensin-converting enzyme 2 and CD147 inhibitor) are major sites based on molecular targets for the management of COVID-19 infection. The possible impact of biologics for the management of COVID19 is promising and includes a wide variety of options such as cytokines, nucleic acid-based therapies targeting virus gene expression, bioengineered and vectored antibodies, and various types of vaccines. This review demonstrates that the available data are not sufficient to suggest any treatment for the eradication of COVID-19 to be used at the clinical level. This article aims to review the roles of existing drugs and drug targets for COVID-19 treatment.
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Project description:The novel coronavirus disease 2019 (COVID-19) pandemic has caused catastrophic damage to human life across the globe along with social and financial hardships. According to the Johns Hopkins University Coronavirus Resource Center, more than 41.3 million people worldwide have been infected, and more than 1,133,000 people have died as of October 22, 2020. At present, there is no available vaccine and a scarcity of efficacious therapies. However, there is tremendous ongoing effort towards identifying effective drugs and developing novel vaccines. Early data from Adaptive COVID-19 Treatment Trials (ACTT) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and compassionate use study have shown promise for remdesivir, leading to emergency authorization by the Food and Drug Administration (FDA) for treatment of hospitalized COVID-19 patients. However, several randomized studies have now shown no benefit or increased adverse events associated with remdesivir treatment. Drug development is a time-intensive process and requires extensive safety and efficacy evaluations. In contrast, drug repurposing is a time-saving and cost-effective drug discovery strategy geared towards using existing drugs instead of de novo drug discovery. Treatments for cancer and COVID-19 often have similar goals of controlling inflammation, inhibiting cell division, and modulating the host microenvironment to control the disease. In this review, we focus on anti-cancer drugs that can potentially be repurposed for COVID-19 and are currently being tested in clinical trials.
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Project description:Corona Virus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a global pandemic. Additionally, the SARS-CoV-2 infection in the patients of Gastric Cancer (GC; the third leading cause of death in the world) pose a great challenge for the health management of the patients. Since there have been uncertainties to develop a new drug against COVID-19, there is an urgent need for repurposing drugs that can target key proteins of both SARS-CoV-2 and GC. The SARS-CoV-2-RdRp protein contains the NiRAN domain, which is known to have kinase-like folds. A docking study of the FDA approved drugs against GC was performed using AutoDock 4.2 and Glide Schrodinger suite 2019 against SARS-CoV-2-RdRp protein. MMGBSA and MD simulation studies were performed to investigate the binding and stability of the inhibitors with the target protein. In this study, we have found 12 kinase inhibitors with high binding energies namely Baricitinib, Brepocitinib, Decernotinib, Fasudil, Filgotinib, GSK2606414, Peficitinib, Ruxolitinib, Tofacitinib, Upadacitinib, Pamapimod and Ibrutinib. These FDA approved drugs against GC can play a key role in the treatment of COVID-19 patients along with GC as comorbidity. We also hypothesize that JAK, ITK, Rho-associated kinases, FGFR2, FYN, PERK, TYK2, p38-MAPK and SYK kinases can be considered as key therapeutic targets in COVID-19 treatment. Taken altogether, we have proposed the SARS-CoV-2-RdRp as a potential therapeutic target through in-silico studies. However, further in-vitro and in-vivo studies are required for the validation of the proposed targets and drugs for the treatment of COVID-19 patients already suffering from GC.
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Project description:A nationwide survey of dentists was carried out in Brazil, a new pandemic epicenter, to analyze how dental care coverage has been affected in public versus private networks, changes in routine and burdens, and how local prevalence of COVID-19 affects dental professionals. Dentists were recruited via email and Instagram®. Responses to a pre-tested questionnaire were collected May 15-24, 2020. COVID-19 case/death counts in the state where respondents work was used to test associations between contextual status and decreases in weekly appointments, fear of contracting COVID-19 at work, and current work status (α = 0.05). Over 10 days, 3,122 responses were received (response rate ~2.1%) from all Brazilian states. Work status was affected for 94%, with less developed regions being more impacted. The pandemic impact on clinical routine was high/very high for 84%, leading to varied changes to clinic infrastructure, personal protective equipment use, and patient screening, as well as increased costs. COVID-19 patients had been seen by 5.3% of respondents; 90% reported fearing contracting COVID-19 at work. Multilevel models showed that greater case and death rates (counted as 1000 cases and 100 deaths per million inhabitants) in one's state increased the odds of being fearful of contracting the disease (18% and 25%). For each additional 1000 cases/100 deaths, the odds of currently not working or treating only emergencies increased by 36% and 58%. The reduction in patients seen weekly was significantly greater in public (38.7±18.6) than in private clinics (22.5±17.8). This study provides early evidence of three major impacts of the pandemic on dentistry: increasing inequalities due to coverage differences between public and private networks; the adoption of new clinical routines, which are associated with an economic burden for dentists; and associations of regional COVID-19 incidence/mortality with fear of contracting the disease at work.
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Project description:By utilizing Optum Life Sciences Claims Data, we constructed Real World Data (RWD) cohorts comprising over 3 million patients and simulated a clinical trial observational study design to evaluate over 200 FDA-approved drugs with COVID-19 repurposing potential, and identified a dozen candidates exhibiting significant reduction in the odds of severe COVID-19 outcomes such as death, intensive care unit (ICU) admission, hospitalization and pneumonia. Notably, certain drug combinations demonstrated effects comparable to those of COVID-19 vaccines. Furthermore, our study revealed a novel finding: a quantitative linear relationship between COVID-19 outcomes and overall patient health risks. This discovery enabled a more precise estimation of drug efficacy using the risk adjustment. The top performing drugs identified include emtricitabine, tenofovir, folic acid, progesterone, estradiol, epinephrine, disulfiram, nitazoxanide and some drug combinations including aspirin-celecoxib.
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