Roflumilast for COVID-19
c19early.org
COVID-19 Treatment Clinical Evidence
COVID-19 involves the interplay of 400+ viral and host proteins and factors, providing many therapeutic targets.
c19early analyzes 6,000+ studies for 210+ treatments—over 17 million hours of research.
Only three high-profit early treatments are approved in the US.
In reality, many treatments reduce risk,
with 25 low-cost treatments approved across 163 countries.
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Naso/
oropharyngeal treatment Effective Treatment directly to the primary source of initial infection. -
Healthy lifestyles Protective Exercise, sunlight, a healthy diet, and good sleep all reduce risk.
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Immune support Effective Vitamins A, C, D, and zinc show reduced risk, as with other viruses.
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Thermotherapy Effective Methods for increasing internal body temperature, enhancing immune system function.
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Systemic agents Effective Many systemic agents reduce risk, and may be required when infection progresses.
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High-profit systemic agents Conditional Effective, but with greater access and cost barriers.
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Monoclonal antibodies Limited Utility Effective but rarely used—high cost, variant dependence, IV/SC admin.
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Acetaminophen Harmful Increased risk of severe outcomes and mortality.
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Remdesivir Harmful Increased mortality with longer followup. Increased kidney and liver injury, cardiac disorders.
Roflumilast may be beneficial for
COVID-19 according to the studies below.
COVID-19 involves the interplay of 400+ viral and host proteins and factors providing many therapeutic targets.
Scientists have proposed 11,000+ potential treatments.
c19early.org analyzes
210+ treatments.
We have not reviewed roflumilast in detail.
, Repositioning Triazoles as Phosphodiesterase‐4 Inhibitors to Suppress
COVID
‐19 Cytokine Storms and Fungal Co‐Infections via Docking and Simulation, Journal of Cellular and Molecular Medicine, doi:10.1111/jcmm.70902
ABSTRACT Severe COVID‐19 cases are often characterised by a hyperinflammatory cytokine storm, which leads to immune dysregulation and increased mortality. Simultaneously, opportunistic fungal infections such as mucormycosis have been increasingly reported, especially in immunocompromised individuals. Triazole antifungals are widely used to treat such infections, but their potential immunomodulatory effects remain underexplored. This study aimed to investigate the off‐target potential of commonly used antifungal triazoles itraconazole, ketoconazole, posaconazole and voriconazole against human phosphodiesterase‐4 (PDE‐4), a key enzyme involved in the regulation of pro‐inflammatory cytokine expression. To our knowledge, this is the first study to explicitly propose and computationally validate the dual role of triazole antifungals as both antifungal and immunomodulatory agents. A computational approach comprising molecular docking, molecular dynamics (MD) simulations and quantum chemical analysis was employed to evaluate the interaction of the selected triazoles with PDE‐4. Binding affinity and interaction stability were compared with roflumilast, a known PDE‐4 inhibitor. Among the tested triazoles, posaconazole exhibited the most favourable binding energy (−44.60 kcal/mol via MM‐GBSA), forming stable interactions with key residues in the catalytic site of PDE‐4, similar to those observed with roflumilast. MD simulations further confirmed the binding stability of posaconazole, as evidenced by favourable RMSD and hydrogen bonding patterns. Quantum chemical analysis indicated strong electrophilicity and reactivity of posaconazole, supporting its potential PDE‐4 inhibitory activity. The findings suggest that certain triazole antifungals, especially posaconazole, may both fight fungal infections and reduce the cytokine storm in severe COVID‐19, offering a promising rapid‐response therapeutic strategy.
, Integration of human organoids single‐cell transcriptomic profiles and human genetics repurposes critical cell type‐specific drug targets for severe COVID ‐19, Cell Proliferation, doi:10.1111/cpr.13558
AbstractHuman organoids recapitulate the cell type diversity and function of their primary organs holding tremendous potentials for basic and translational research. Advances in single‐cell RNA sequencing (scRNA‐seq) technology and genome‐wide association study (GWAS) have accelerated the biological and therapeutic interpretation of trait‐relevant cell types or states. Here, we constructed a computational framework to integrate atlas‐level organoid scRNA‐seq data, GWAS summary statistics, expression quantitative trait loci, and gene–drug interaction data for distinguishing critical cell populations and drug targets relevant to coronavirus disease 2019 (COVID‐19) severity. We found that 39 cell types across eight kinds of organoids were significantly associated with COVID‐19 outcomes. Notably, subset of lung mesenchymal stem cells increased proximity with fibroblasts predisposed to repair COVID‐19‐damaged lung tissue. Brain endothelial cell subset exhibited significant associations with severe COVID‐19, and this cell subset showed a notable increase in cell‐to‐cell interactions with other brain cell types, including microglia. We repurposed 33 druggable genes, including IFNAR2, TYK2, and VIPR2, and their interacting drugs for COVID‐19 in a cell‐type‐specific manner. Overall, our results showcase that host genetic determinants have cellular‐specific contribution to COVID‐19 severity, and identification of cell type‐specific drug targets may facilitate to develop effective therapeutics for treating severe COVID‐19 and its complications.