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 μM 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 (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT03034135">NCT03034135</ext-link>, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT00742911">NCT00742911</ext-link>). A preliminary mechanism is proposed to rationalize the observed promotional effect.