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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
New studies were performed in Calu3 cells and some of the data has been refined. One additional author has also been included
List of abbreviations
- AMPK
- AMP-activated protein kinase
- ACC
- Acetyl CoA carboxylase
- AICAR
- 5-Aminoimidazole-4-carboxamide ribonucleotide
- CC
- Compound C
- COVID-19
- Coronavirus disease 19
- hpi
- hours post infection
- IFIT1
- Interferon-induced protein with tetratricopeptide repeats 1
- MOI
- Multiplicity of infection
- PPARs
- peroxisome proliferator-activated receptors
- SARS-CoV-2
- Severe acute respiratory syndrome coronavirus 2
- SREBPs
- Sterol regulatory element-binding proteins
- TCID50/90
- 50%/ 90% Tissue culture infective dose
