ArticleMedical hypotheses2020
The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases?
Article in Medical hypotheses, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 61 citations in OpenAlex.
- Effect of early prophylactic heparin use on prognosis in critically ill patients with acute pancreatitis: a retrospective cohort study.Scientific reports · 2025Article
- Ocular microvascular changes in COVID-19: role of hypoxia, D-dimer, IL-6 and systemic treatment.Pharmacological reports : PR · 2025Article
- Endothelial growth media components alter SARS-CoV-2 spike-directed growth kinetics.Journal of virological methods · 2025Article
- Promising Drug Fondaparinux for the Treatment of COVID-19: an In Silico Analysis of Low Molecular Weight Heparin, Direct Oral Anticoagulant, and Antiplatelet Drug Interactions with Host Protease Furin.Cardiovascular drugs and therapy · 2024Article
- Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection.Nature communications · 2023Article
- Endothelial Dysfunction in COVID-19: Potential Mechanisms and Possible Therapeutic Options.Life (Basel, Switzerland) · 2022Review
- Tinzaparin-a review of its molecular profile, pharmacology, special properties, and clinical uses.European journal of clinical pharmacology · 2022Review
- Epidemiological characteristics, clinical relevance, and risk factors of thromboembolic complications among patients with COVID-19 pneumonia at A teaching hospital: Retrospective observational study.Annals of medicine and surgery (2012) · 2022Article
- Observational
- Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors.International journal of molecular sciences · 2022Article
- Horizons of Heparin Therapy in COVID-19 and Pandemic-Related Diseases.Journal of evolutionary biochemistry and physiology · 2022Article
- Consensus docking and MM-PBSA computations identify putative furin protease inhibitors for developing potential therapeutics against COVID-19.Structural chemistry · 2022Article
- Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection.Biochemistry (Moscow) Supplement. Series B, Biomedical chemistry · 2022Article
- SARS-CoV-2 spike protein: Site-specific breakpoints for the development of COVID-19 vaccines.Journal of King Saud University. Science · 2021Review
- Pathomechanisms, therapeutic targets and potent inhibitors of some beta-coronaviruses from bench-to-bedside.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2021Review
- Heparin: A simplistic repurposing to prevent SARS-CoV-2 transmission in light of its in-vitro nanomolar efficacy.International journal of biological macromolecules · 2021Article
- Treatment of COVID-19 by stage: any space left for mesenchymal stem cell therapy?Regenerative medicine · 2021Review
- Thrombin Inhibition by Argatroban: Potential Therapeutic Benefits in COVID-19.Cardiovascular drugs and therapy · 2021Review
- Deep vein thrombosis with pulmonary thromboembolism in a case of severe COVID-19 pneumonia.BMJ case reports · 2021Article
- COVID-19 endocrinopathy with hindsight from SARS.American journal of physiology. Endocrinology and metabolism · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently, our world is facing the 2019 Novel Coronavirus (COVID-19) outbreak and tremendous efforts are made for developing drugs to treat and vaccines to prevent the disease. At present, there is no specific antiviral drug or vaccine for COVID-19. The pathogenic infectivity of the virus requires the S1 subunit of the spike (S) protein to bind the host cell receptor, angiontensin converting enzyme (ACE2). While the binding to host cell receptor is the first step of infection, the entrance of the virus into the cell needs the cleavage of S1-S2 subunits to expose S2 for fusion to cell membrane via host proteases including cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, trypsin and factor Xa. Previous in vitro studies have shown that factor Xa inhibition can decrease viral infectivity. We suppose that host cell proteases including furin (as expressed highly in lungs), factor Xa and cathepsin are possible targets to decrease viral burden, therefore unfractioned heparin and low molecular weight heparin-LMWH (specifically dalteparin and tinzaparin for their anti inflammatory action) can be potential inhibitors of multiple endoproteases involved in virus infectivity. Our hypothesis needs to be tested in in vitro and clinical studies, however as we are in an urgent situation as the burden of SARS-CoV2 is increasing all around the world, we recommend the usage of unfractioned heparin or LMWH in intensive care unit (ICU) and non-ICU hospitalized patients with the risk-benefit judgement of the clinician. Whether our hypothesis is clinically applicable and successful in decreasing viral infection will be evaluated for further studies.
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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.