ArticleInternational journal of antimicrobial agents2020
Amantadine disrupts lysosomal gene expression: A hypothesis for COVID19 treatment.
Article in International journal of antimicrobial agents, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04894617 (Amantadine for COVID-19), which is not on this map. Cited by 73 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Amantadine for COVID-19: A Randomized, Placebo Controlled, Double-blinded, Clinical Trial
Who cites it
73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 citations in OpenAlex.
- A Systematic Review of the Global Intervention for SARS-CoV-2 Combating: From Drugs Repurposing to Molnupiravir Approval.Drug design, development and therapy · 2022Pooled it
- COVID-19 and Parkinson's Disease: What Do We Know So Far?Journal of Parkinson's disease · 2021Pooled it
- Amantadine in unvaccinated patients with early, mild to moderate COVID-19: A randomized, placebo-controlled, double-blind trial.European journal of neurology · 2024Trial
- Drug Repurposing as a Broad-Spectrum Strategy Against Coronaviruses: Frontiers in Mechanisms and Clinical Translation.Viruses · 2026Review
- Cathepsin L and transmembrane serine protease 11E mediate trypsin-independent entry of porcine deltacoronavirus into Huh7 cells.Journal of virology · 2025Article
- Navigating the COVID-19 Therapeutic Landscape: Unveiling Novel Perspectives on FDA-Approved Medications, Vaccination Targets, and Emerging Novel Strategies.Molecules (Basel, Switzerland) · 2024Review
- Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.Molecular aspects of medicine · 2023Review
- Ethical challenges of clinical trials with a repurposed drug in outbreaks.Medicine, health care, and philosophy · 2023Article
- Spatial Distribution of SARS-CoV-2 Receptors and Proteases in Testicular Cells.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2023Article
- Receptors and Cofactors That Contribute to SARS-CoV-2 Entry: Can Skin Be an Alternative Route of Entry?International journal of molecular sciences · 2023Review
- SARS-CoV-2 infection alkalinizes the ERGIC and lysosomes through the viroporin activity of the viral envelope protein.Journal of cell science · 2023Article
- Autophagy in Inflammatory Response against SARS-CoV-2.International journal of molecular sciences · 2023Review
- Links between COVID-19 and Parkinson's disease/Alzheimer's disease: reciprocal impacts, medical care strategies and underlying mechanisms.Translational neurodegeneration · 2023Review
- COVID-19 and neurological disorders: what might connect Parkinson's disease to SARS-CoV-2 infection.Frontiers in neurology · 2023Review
- Adamantanes for the treatment of neurodegenerative diseases in the presence of SARS-CoV-2.Frontiers in neuroscience · 2023Review
- The development of COVID-19 treatment.Frontiers in immunology · 2023Review
- Advances of CRISPR-Cas13 system in COVID-19 diagnosis and treatment.Genes & diseases · 2022Review
- Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022Review
- Psychotic Disorders in the Course of SARS-CoV-2 Infection or Uncomplicated Amantadine Treatment?-Case Report.International journal of environmental research and public health · 2022Article
- Overview of Antiviral Drug Therapy for COVID-19: Where Do We Stand?Biomedicines · 2022Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-coronavirus 2 is the causal agent of the COVID-19 outbreak. SARS-Cov-2 entry into a cell is dependent upon binding of the viral spike (S) protein to cellular receptor and on cleavage of the spike protein by the host cell proteases such as Cathepsin L and Cathepsin B. CTSL/B are crucial elements of lysosomal pathway and both enzymes are almost exclusively located in the lysosomes. CTSL disruption offers potential for CoVID-19 therapies. The mechanisms of disruption include: decreasing expression of CTSL, direct inhibition of CTSL activity and affecting the conditions of CTSL environment (increase pH in the lysosomes). We have conducted a high throughput drug screen gene expression analysis to identify compounds that would downregulate the expression of CTSL/CTSB. One of the top significant results shown to downregulate the expression of the CTSL gene is amantadine (10uM). Amantadine was approved by the US Food and Drug Administration in 1968 as a prophylactic agent for influenza and later for Parkinson's disease. It is available as a generic drug. Amantadine in addition to downregulating CTSL appears to further disrupt lysosomal pathway, hence, interfering with the capacity of the virus to replicate. It acts as a lysosomotropic agent altering the CTSL functional environment. We hypothesize that amantadine could decrease the viral load in SARS-CoV-2 positive patients and as such it may serve as a potent therapeutic decreasing the replication and infectivity of the virus likely leading to better clinical outcomes. Clinical studies will be needed to examine the therapeutic utility of amantadine in COVID-19 infection.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.