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A Mathematical Model of Metformin Action on COVID-19 Risk Infection in Cardiovascular Diabetic Patients Studied by FTIR Spectroscopy

Mylonas et al., International Journal of Molecular Sciences, doi:10.3390/ijms26136332, Jun 2025
https://c19early.org/mylonas.html
Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020, now with p < 0.00000000001 from 105 studies.
No treatment is 100% effective. Protocols combine treatments.
5,900+ studies for 173 treatments. c19early.org
Ex vivo Fourier-transform infrared (FTIR) spectroscopy of coronary-artery tissue and fractional-calculus risk modelling showing that metformin use is associated with lower predicted COVID-19 infection and mortality than insulin or thiazolidinediones in type-2 diabetic cardiovascular patients. Authors propose that metformin’s four NH groups form hydrogen bonds with the SARS-CoV-2 spike glycoprotein, directly blocking attachment, while its AMP-kinase activation and antioxidant properties lower advanced glycation end-products, indirectly reducing viral entry.
Mylonas et al., 30 Jun 2025, peer-reviewed, 6 authors.
Ex Vivo studies are an important part of preclinical research, however results may be very different in vivo.
A Mathematical Model of Metformin Action on COVID-19 Risk Infection in Cardiovascular Diabetic Patients Studied by FTIR Spectroscopy
Evangelos Mylonas, Christina Mamareli, Michael Filippakis, Ioannis Mamarelis, Jane Anastassopoulou, Theophile Theophanides
International Journal of Molecular Sciences, doi:10.3390/ijms26136332
Several studies have revealed that patients with type 2 diabetes (T2D) infected with COVID-19 who were medicated with metformin showed higher recovery rates than those administered other antidiabetic drugs. To determine the mechanism of action of antidiabetic drugs against COVID-19, we developed a mathematical model that was based on the number of infected and recovered T2D patients. Moreover, the "diagnostic frequencies" of the infected T2D patients, determined using Fourier-Transform Infrared (FTIR) spectroscopy, were very helpful. In particular, the band at 1775 cm -1 , attributed to IgG antibodies, could be used as a "diagnostic frequency" for COVID-19 infection. The increased intensity of the band of vC-O-C sugar moieties suggests an increased number of OH chemical groups that enhance the binding sites of SARS-CoV-2 spike protein for entering host cells. The changes were more pronounced in patients medicated with thiazolidinediones than those using insulin and metformin. Both FTIR spectra and the developed mathematical model confirmed that patients using thiazolidinediones showed a higher risk of COVID-19 infection and mortality. The data support the hypothesis that the NH chemical groups of metformin molecules interact directly through the SARS-CoV-2 spike protein, preventing the entry of COVID-19 into the host membrane cells. Indirectly, metformin inhibits the host binding sites for COVID-19 entry by lowering AGE production.
Author Contributions: E.M., mathematical model simulation, modeling. M.F., supervision of mathematical model simulation. C.M., literature on diabetes-COVID-19 interactions. I.M., supervision of the cardiovascular contribution of patients. J.A., supervision, designing, methodology, FTIR interpretation. T.T., review, editing, FTIR interpretation of characteristic vibrations. All authors have read and agreed to the published version of the manuscript. Funding: This study did not receive any external funding. Conflicts of Interest: The authors declare no conflicts of interest. Abbreviations The following abbreviations are used in the manuscript: ACE2 Angiotensin
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DOI record: { "DOI": "10.3390/ijms26136332", "ISSN": [ "1422-0067" ], "URL": "http://dx.doi.org/10.3390/ijms26136332", "abstract": "<jats:p>Several studies have revealed that patients with type 2 diabetes (T2D) infected with COVID-19 who were medicated with metformin showed higher recovery rates than those administered other antidiabetic drugs. To determine the mechanism of action of antidiabetic drugs against COVID-19, we developed a mathematical model that was based on the number of infected and recovered T2D patients. Moreover, the “diagnostic frequencies” of the infected T2D patients, determined using Fourier-Transform Infrared (FTIR) spectroscopy, were very helpful. In particular, the band at 1775 cm−1, attributed to IgG antibodies, could be used as a “diagnostic frequency” for COVID-19 infection. The increased intensity of the band of vC-O-C sugar moieties suggests an increased number of OH chemical groups that enhance the binding sites of SARS-CoV-2 spike protein for entering host cells. The changes were more pronounced in patients medicated with thiazolidinediones than those using insulin and metformin. Both FTIR spectra and the developed mathematical model confirmed that patients using thiazolidinediones showed a higher risk of COVID-19 infection and mortality. The data support the hypothesis that the NH chemical groups of metformin molecules interact directly through the SARS-CoV-2 spike protein, preventing the entry of COVID-19 into the host membrane cells. Indirectly, metformin inhibits the host binding sites for COVID-19 entry by lowering AGE production.</jats:p>", "alternative-id": [ "ijms26136332" ], "author": [ { "affiliation": [ { "name": "Department of Digital Systems, University of Piraeus, 80 M. Karaoli & A. 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Please send us corrections, updates, or comments. c19early involves the extraction of 200,000+ 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. IMA and WCH provide treatment protocols.
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