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, NCT00742911). A preliminary mechanism is proposed to rationalize the observed promotional effect.

中文翻译：

---

葡萄糖酸铜 (II) 在体外增强双硫仑的抗 SARS-CoV-2 作用

双硫仑是一种已有 70 年历史的抗酒精中毒药物，而葡萄糖酸铜 (II) (Cu(Glu) ₂ ) 是一种常用的食品添加剂或铜补充剂。在这里我们披露，与单独使用双硫仑或葡萄糖酸铜 (II) 相比，双硫仑和葡萄糖酸铜 (II) 的组合在细胞水平上显着增强了抗 SARS-CoV-2 活性。双硫仑和葡萄糖酸铜 (II) 的 1:1 混合物显示 EC ₅₀在细胞水平上对 SARS-CoV-2 的值是 154 nM，远低于单独报告的双硫仑的 17.45 μM。值得注意的是，之前的临床试验表明，每天服用 250 毫克双硫仑（0.843 毫摩尔）和 8 毫克葡萄糖酸铜（II）（0.0176 毫摩尔）口服胶囊的组合耐受性良好（NCT03034135，NCT00742911）。提出了一种初步机制来合理化观察到的促销效果。