Copper(II) Gluconate Boosts the Anti-SARS-CoV-2 Effect of Disulfiram in Vitro

Disulfiram is a 70-year-old anti-alcoholism drug, while copper(II) gluconate (Cu(Glu)2) is a commonly used food additive or copper supplement. Here we disclose that the combination of disulfiram and copper(II) gluconate drastically enhances the anti-SARS-CoV-2 activity at the cellular level as compared to disulfiram or copper(II) gluconate alone. A 1:1 mixture of disulfiram and copper(II) gluconate shows an EC50 value of 154 nM against SARS-CoV-2 at the cellular level, much lower than the 17.45 M reported for disulfiram alone. Notably, previous clinical trials have shown that a combination of 250 mg disulfiram (0.843 mmol) and 8 mg copper(II) gluconate (0.0176 mmol) oral capsules per day is well tolerated (NCT03034135, NCT00742911). A preliminary mechanism is proposed to rationalize the observed promotional effect.