key: cord-0272909-npknibr8
authors: Xu, Luyan; Xu, Wei; Zhao, Simeng; Zhao, Suwen; Lu, Lu; Lin, Bo-Lin
title: Copper(II) Gluconate Boosts the Anti-SARS-CoV-2 Effect of Disulfiram in vitro
date: 2021-09-18
journal: bioRxiv
DOI: 10.1101/2021.09.17.460613
sha: d66b49b0f4023a3cdf1e153a90854ce73792cc6f
doc_id: 272909
cord_uid: npknibr8

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

measurements showed that the EC50 of the 1:1 combination of disulfiram and copper(II) gluconate against 23 SARS-COV-2 at the cellular level was 154 nM (Figure 1) , significantly lower than that of disulfiram 24 alone (17.45 μM). 1 25 Table 1 . Inhibitory ratio of various chemicals by single-point inhibition assay at 10 μM onto SARS-26 COV-2 at the cellular level, determined by qRT-PCR analysis. n = 3 biological replicates. 27 As shown in Figure 1 , the mixture of disulfiram and copper(II) gluconate had much improved 29 inhibitory activity of against SARS-CoV-2 infection with an EC50 of 154 nM (Figure 1) . The results 30

showed that viral RNA levels of the mixture of disulfiram and copper(II) gluconate were significantly 31 lower than that of the non-mixture groups (disulfiram or copper(II) gluconate). 32 UV-vis spectroscopy revealed that the appearance and growth of an absorption peak at 433 nm from 33 

A clinical isolate of SARS-CoV-2(SARS-CoV-2 / SH01 / human / 2020 / CHN，GenBank MT121215). 73

The virus was purified by phagocytosis, reproduced in Vero-E6 cells, and stored in -80 ℃ for future use. 

Multi-targeting 91 of functional cysteines in multiple conserved SARS-CoV-2 domains by clinically safe Zn-ejectors

Targeted Oxidation Strategy (TOS) for potential inhibition of 94 coronaviruses by Disulfiram -a 70-year old anti-alcoholism drug

A computational evaluation of targeted oxidation strategy (TOS) 97 for potential inhibition of SARS-CoV-2 by disulfiram and analogues

Universal anticancer Cu(DTC) 2 99 discriminates between thiols and zinc(II) thiolates oxidatively

Qian Wang of Core Facility of Microbiology and Parasitology of Fudan University. We 103 are very grateful to

Medical College of Fudan University for their continuous support. This work was supported by the 105 National Natural Science Foundation of China

The authors declare no competing interests 108 109 110