Zika virus (ZIKV), a single-stranded RNA virus, is a mosquito transmitted flavivirus. A study using HUVECs and human retinal vascular endothelial cells (HRvECs) showed that AMPK restricts the replication of ZIKV in the endothelial cells [16]. Activation of AMPK with the help of two well-known AMPK activators, metformin and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) led to attenuation of ZIKV replication. Activated AMPK further potentiated the expression of certain genes with known antiviral properties such as IFNs, OAS2, ISG15, and MX1 while inhibiting inflammatory mediators like TNF-α and CCL5. It would be useful to explore whether the same is observed for SARS-CoV-2. A recent study has reported that inhibition of glycolysis by non-toxic concentration of 2-DG completely attenuated SARS-CoV-2 replication in Caco-2 cells [17]. All of these indicate towards a possible frontline role of metformin against COVID-19.