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Deguelin for COVID-19

Deguelin has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Ko et al., Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19, bioRxiv, doi:10.1101/2020.02.25.965582
AbstractTherapeutic options for coronavirus remain limited. To address this unmet medical need, we screened 5,406 compounds, including United States Food and Drug Administration (FDA)- approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6. Time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI>100), atovaquone, an anti-malarial (TI>34), and ciclosonide, an inhalable corticosteroid (TI>6). Furthermore, utilizing the severe acute respiratory syndrome CoV-2 (SARS-CoV-2), combinations of remedesivir with selected dugs were evaluated, which identified ciclosonide and nelfinavir to be additive and synergistic drugs in vitro, respectively. Together, we screened FDA-approved drugs using patient-derived MERS-CoV, triaged hits to discriminate between early and late viral life cycle inhibitors, confirmed selected drugs using SARS-CoV-2, and demonstrated the added value of selected medications in combination with remedesivir. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses.
Sperry et al., Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients, PLOS Computational Biology, doi:10.1371/journal.pcbi.1011050 (Table 2)
Drug repurposing requires distinguishing established drug class targets from novel molecule-specific mechanisms and rapidly derisking their therapeutic potential in a time-critical manner, particularly in a pandemic scenario. In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. However, it is unknown if different statins exhibit consistent function or may have varying therapeutic benefit. A Bayesian network tool was used to predict drugs that shift the host transcriptomic response to SARS-CoV-2 infection towards a healthy state. Drugs were predicted using 14 RNA-sequencing datasets from 72 autopsy tissues and 465 COVID-19 patient samples or from cultured human cells and organoids infected with SARS-CoV-2. Top drug predictions included statins, which were then assessed using electronic medical records containing over 4,000 COVID-19 patients on statins to determine mortality risk in patients prescribed specific statins versus untreated matched controls. The same drugs were tested in Vero E6 cells infected with SARS-CoV-2 and human endothelial cells infected with a related OC43 coronavirus. Simvastatin was among the most highly predicted compounds (14/14 datasets) and five other statins, including atorvastatin, were predicted to be active in > 50% of analyses. Analysis of the clinical database revealed that reduced mortality risk was only observed in COVID-19 patients prescribed a subset of statins, including simvastatin and atorvastatin. In vitro testing of SARS-CoV-2 infected cells revealed simvastatin to be a potent direct inhibitor whereas most other statins were less effective. Simvastatin also inhibited OC43 infection and reduced cytokine production in endothelial cells. Statins may differ in their ability to sustain the lives of COVID-19 patients despite having a shared drug target and lipid-modifying mechanism of action. These findings highlight the value of target-agnostic drug prediction coupled with patient databases to identify and clinically evaluate non-obvious mechanisms and derisk and accelerate drug repurposing opportunities.
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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