Pilocarpine for COVID-19
Pilocarpine has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
A clustering and graph deep learning-based framework for COVID-19 drug repurposing, arXiv, doi:10.48550/arXiv.2306.13995 ,
Drug repurposing (or repositioning) is the process of finding new therapeutic uses for drugs already approved by drug regulatory authorities (e.g., the Food and Drug Administration (FDA) and Therapeutic Goods Administration (TGA)) for other diseases. This involves analyzing the interactions between different biological entities, such as drug targets (genes/proteins and biological pathways) and drug properties, to discover novel drug-target or drug-disease relations. Artificial intelligence methods such as machine learning and deep learning have successfully analyzed complex heterogeneous data in the biomedical domain and have also been used for drug repurposing. This study presents a novel unsupervised machine learning framework that utilizes a graph-based autoencoder for multi-feature type clustering on heterogeneous drug data. The dataset consists of 438 drugs, of which 224 are under clinical trials for COVID-19 (category A). The rest are systematically filtered to ensure the safety and efficacy of the treatment (category B). The framework solely relies on reported drug data, including its pharmacological properties, chemical/physical properties, interaction with the host, and efficacy in different publicly available COVID-19 assays. Our machine-learning framework reveals three clusters of interest and provides recommendations featuring the top 15 drugs for COVID-19 drug repurposing, which were shortlisted based on the predicted clusters that were dominated by category A drugs. The anti-COVID efficacy of the drugs should be verified by experimental studies. Our framework can be extended to support other datasets and drug repurposing studies, given open-source code and data availability.
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.
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