PT - JOURNAL ARTICLE AU - Haripriya Parthasarathy AU - Dixit Tandel AU - Abdul Hamid Siddiqui AU - Krishnan H. Harshan TI - Metformin Suppresses SARS-CoV-2 in Cell Culture AID - 10.1101/2021.11.18.469078 DP - 2022 Jan 01 TA - bioRxiv PG - 2021.11.18.469078 4099 - http://biorxiv.org/content/early/2022/07/29/2021.11.18.469078.short 4100 - http://biorxiv.org/content/early/2022/07/29/2021.11.18.469078.full AB - 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.Competing Interest StatementThe authors have declared no competing interest.AMPKAMP-activated protein kinaseACCAcetyl CoA carboxylaseAICAR5-Aminoimidazole-4-carboxamide ribonucleotideCCCompound CCOVID-19Coronavirus disease 19hpihours post infectionIFIT1Interferon-induced protein with tetratricopeptide repeats 1MOIMultiplicity of infectionPPARsperoxisome proliferator-activated receptorsSARS-CoV-2Severe acute respiratory syndrome coronavirus 2SREBPsSterol regulatory element-binding proteinsTCID50/9050%/ 90% Tissue culture infective dose