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 ([NCT03034135][1], [NCT00742911][2]). A preliminary mechanism is proposed to rationalize the observed promotional effect. ### Competing Interest Statement The authors have declared no competing interest. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03034135&atom=%2Fbiorxiv%2Fearly%2F2021%2F10%2F01%2F2021.09.17.460613.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00742911&atom=%2Fbiorxiv%2Fearly%2F2021%2F10%2F01%2F2021.09.17.460613.atom