Synergistic Inhibition of SARS-CoV-2 Replication Using Disulfiram/Ebselen and Remdesivir.

ABSTRACT: The SARS-CoV-2 replication and transcription complex (RTC) comprising nonstructural protein (nsp) 2-16 plays crucial roles in viral replication, reducing the efficacy of broad-spectrum nucleoside analog drugs such as remdesivir and evading innate immune responses. Most studies target a specific viral component of the RTC such as the main protease or the RNA-dependent RNA polymerase. In contrast, our strategy is to target multiple conserved domains of the RTC to prevent SARS-CoV-2 genome replication and to create a high barrier to viral resistance and/or evasion of antiviral drugs. We show that the clinically safe Zn-ejector drugs disulfiram and ebselen can target conserved Zn²⁺ sites in SARS-CoV-2 nsp13 and nsp14 and inhibit nsp13 ATPase and nsp14 exoribonuclease activiti

SUBMITTER: Chen T 

PROVIDER: S-EPMC8009100 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature