Metformin Suppresses SARS-CoV-2 in Cell Culture
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Abstract
Comorbidities such as diabetes worsen COVID-19 severity and recovery. Metformin, a first-line medication for type 2 diabetes, has antiviral properties and certain studies have also indicated its prognostic potential in COVID-19. Here, we report that metformin significantly inhibits SARS-CoV-2 growth in cell culture models. First, a steady increase in AMPK phosphorylation was detected as infection progressed, suggesting its important role during viral infection. Activation of AMPK in Calu3 and Caco2 cell lines using metformin revealed that metformin suppresses SARS-CoV-2 infectious titers up to 99%, in both naïve as well as infected cells. TCID50 values from dose-variation studies in infected cells were found to be 0.8 and 3.5 mM in Calu3 and Caco2 cells, respectively. Role of AMPK in metformin’s antiviral suppression was further confirmed using other pharmacological compounds, AICAR and Compound C. Collectively, our study demonstrates that metformin is effective in limiting the replication of SARS-CoV-2 in cell culture and thus possibly could offer double benefits s diabetic COVID-19 patients by lowering both blood glucose levels and viral load.
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SciScore for 10.1101/2021.11.18.469078: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Anti-AMPKα antibody was procured from CST. Anti-AMPKαsuggested: NoneGAPDH, β-tubulin, and anti-Nucleocapsid antibodies were from ThermoFisher Scientific. GAPDH,suggested: NoneGAPDHsuggested: Noneβ-tubulinsuggested: Noneanti-Nucleocapsidsuggested: NoneExperimental Models: Cell Lines Sentences Resources Cell culture and reagents: Caco2, Huh7, and Vero cells were grown in DMEM supplemented with FBS, and Pen Strep, at 37°C and 5% CO2. Huh7suggested: NoneVerosuggested: NoneCell viability assay: … SciScore for 10.1101/2021.11.18.469078: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Anti-AMPKα antibody was procured from CST. Anti-AMPKαsuggested: NoneGAPDH, β-tubulin, and anti-Nucleocapsid antibodies were from ThermoFisher Scientific. GAPDH,suggested: NoneGAPDHsuggested: Noneβ-tubulinsuggested: Noneanti-Nucleocapsidsuggested: NoneExperimental Models: Cell Lines Sentences Resources Cell culture and reagents: Caco2, Huh7, and Vero cells were grown in DMEM supplemented with FBS, and Pen Strep, at 37°C and 5% CO2. Huh7suggested: NoneVerosuggested: NoneCell viability assay: Effect of different doses of metformin on viability of mock and infected Caco2 cells was measured using MTT assay. Caco2suggested: CLS Cat# 300137/p1665_CaCo-2, RRID:CVCL_0025)Software and Algorithms Sentences Resources Quantification was performed using ImageJ (Schneider et al., 2012). ImageJsuggested: (ImageJ, RRID:SCR_003070)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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