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Edoxaban for COVID-19

Edoxaban has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Olivera et al., Edoxaban Versus Low-Molecular-Weight Heparin in Hospitalized COVID-19 Patients With Atrial Fibrillation, Clinical and Applied Thrombosis/Hemostasis, doi:10.1177/10760296231180865
Objective During the first wave of the SARS-CoV-2 pandemic, management of anticoagulation therapy in hospitalized patients with atrial fibrillation (AF) was simplified to low-molecular-weight heparin (LMWH) followed by oral anticoagulation, mainly owing to the risk of drug–drug interactions. However, not all oral anticoagulants carry the same risk. Methods Observational, retrospective, and multicenter study that consecutively included hospitalized patients with AF anticoagulated with LMWH followed by oral anticoagulation or edoxaban concomitantly with empirical COVID-19 therapy. Time-to-event (mortality, total bleeds, and admissions to ICU) curves, using an unadjusted Kaplan-Meier method and Cox regression model adjusted for potential confounders were constructed. Results A total of 232 patients were included (80.3 ± 7.7 years, 50.0% men, CHA2DS2-VASc 4.1 ± 1.4; HAS-BLED 2.6 ± 1.0). During hospitalization, patients were taking azithromycin (98.7%), hydroxychloroquine (89.7%), and ritonavir/lopinavir (81.5%). The mean length of hospital stay was 14.6 ± 7.2 days, and total follow-up was 31.6 ± 13.4 days; 12.9% of patients required admission to ICU, 18.5% died, and 9.9% had a bleeding complication (34.8% major bleeding). Length of hospital stay was longer in patients taking LMWH (16.0 ± 7.7 vs 13.3 ± 6.5 days; P = .005), but mortality and total bleeds were similar in patients treated with edoxaban and those treated with LMWH followed by oral anticoagulation. Conclusions Mortality rates, arterial and venous thromboembolic complications, and bleeds did not significantly differ between AF patients receiving anticoagulation therapy with edoxaban or LMWH followed by oral anticoagulation. However, the duration of hospitalization was significantly lower with edoxaban. Edoxaban had a similar therapeutic profile to LMWH followed by oral anticoagulation and may provide additional benefits.
Rensi et al., Homology Modeling of TMPRSS2 Yields Candidate Drugs That May Inhibit Entry of SARS-CoV-2 into Human Cells, American Chemical Society (ACS), doi:10.26434/chemrxiv.12009582.v1
The most rapid path to discovering treatment options for the novel coronavirus SARS-CoV-2 is to find existing medications that are active against the virus. We have focused on identifying repurposing candidates for the transmembrane serine protease family member II (TMPRSS2), which is critical for entry of coronaviruses into cells. Using known 3D structures of close homologs, we created seven homology models. We also identified a set of serine protease inhibitor drugs, generated several conformations of each, and docked them into our models. We used three known chemical (non-drug) inhibitors and one validated inhibitor of TMPRSS2 in MERS as benchmark compounds and found six compounds with predicted high binding affinity in the range of the known inhibitors. We also showed that a previously published weak inhibitor, Camostat, had a significantly lower binding score than our six compounds. All six compounds are anticoagulants with significant and potentially dangerous clinical effects and side effects. Nonetheless, if these compounds significantly inhibit SARS-CoV-2 infection, they could represent a potentially useful clinical tool.
Tsegay et al., A repurposed drug screen identifies compounds that inhibit the binding of the COVID-19 spike protein to ACE2, bioRxiv, doi:10.1101/2021.04.08.439071
AbstractRepurposed drugs that block the interaction between the SARS-CoV-2 spike protein and its receptor ACE2 could offer a rapid route to novel COVID-19 treatments or prophylactics. Here, we screened 2701 compounds from a commercial library of drugs approved by international regulatory agencies for their ability to inhibit the binding of recombinant, trimeric SARS-CoV-2 spike protein to recombinant human ACE2. We identified 56 compounds that inhibited binding by <90%, measured the EC50 of binding inhibition, and computationally modeled the docking of the best inhibitors to both Spike and ACE2. These results highlight an effective screening approach to identify compounds capable of disrupting the Spike-ACE2 interaction as well as identifying several potential inhibitors that could serve as templates for future drug discovery efforts.
Tsegay et al., A Repurposed Drug Screen Identifies Compounds That Inhibit the Binding of the COVID-19 Spike Protein to ACE2, Frontiers in Pharmacology, doi:10.3389/fphar.2021.685308
Repurposed drugs that block the interaction between the SARS-CoV-2 spike protein and its receptor ACE2 could offer a rapid route to novel COVID-19 treatments or prophylactics. Here, we screened 2,701 compounds from a commercial library of drugs approved by international regulatory agencies for their ability to inhibit the binding of recombinant, trimeric SARS-CoV-2 spike protein to recombinant human ACE2. We identified 56 compounds that inhibited binding in a concentration-dependent manner, measured the IC50of binding inhibition, and computationally modeled the docking of the best inhibitors to the Spike-ACE2 binding interface. The best candidates were Thiostrepton, Oxytocin, Nilotinib, and Hydroxycamptothecin with IC50’s in the 4–9 μM range. These results highlight an effective screening approach to identify compounds capable of disrupting the Spike-ACE2 interaction, as well as identify several potential inhibitors of the Spike-ACE2 interaction.
Oliver et al., Different drug approaches to COVID-19 treatment worldwide: an update of new drugs and drugs repositioning to fight against the novel coronavirus, Therapeutic Advances in Vaccines and Immunotherapy, doi:10.1177/25151355221144845
According to the World Health Organization (WHO), in the second half of 2022, there are about 606 million confirmed cases of COVID-19 and almost 6,500,000 deaths around the world. A pandemic was declared by the WHO in March 2020 when the new coronavirus spread around the world. The short time between the first cases in Wuhan and the declaration of a pandemic initiated the search for ways to stop the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or to attempt to cure the disease COVID-19. More than ever, research groups are developing vaccines, drugs, and immunobiological compounds, and they are even trying to repurpose drugs in an increasing number of clinical trials. There are great expectations regarding the vaccine’s effectiveness for the prevention of COVID-19. However, producing sufficient doses of vaccines for the entire population and SARS-CoV-2 variants are challenges for pharmaceutical industries. On the contrary, efforts have been made to create different vaccines with different approaches so that they can be used by the entire population. Here, we summarize about 8162 clinical trials, showing a greater number of drug clinical trials in Europe and the United States and less clinical trials in low-income countries. Promising results about the use of new drugs and drug repositioning, monoclonal antibodies, convalescent plasma, and mesenchymal stem cells to control viral infection/replication or the hyper-inflammatory response to the new coronavirus bring hope to treat the disease.
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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