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. 2021 Mar 26;4(2):898–907. doi: 10.1021/acsptsci.1c00022

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© 2021 American Chemical Society

This article is made available via the ACS COVID-19 subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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Disulfiram and ebselen can target multiple SARS-CoV-2 nsps to block the viral polyprotein cleavage and RNA replication/transcription. These Zn²⁺-ejector drugs target PL^pro of nsp3 and M^pro of nsp5 to inhibit viral polypeptide proteolysis. They also directly target nsp10, nsp13, and nsp14 as well as indirectly target nsp12 and nsp16 to inhibit viral RNA genome replication and translation of the structural and accessory viral proteins. They can act in concert with remdesivir to synergistically inhibit SARS-CoV-2 replication.