AI Article Synopsis
- - The COVID-19 pandemic, caused by the SARS-CoV-2 virus, presents a significant global health threat that highlights the urgent need for new antiviral treatments alongside vaccines.
- - Researchers focused on the virus's main protease (Mpro) as a key target for developing antiviral drugs due to its essential role in virus replication and immune evasion.
- - An improved fluorescence-based assay was created to efficiently screen for Mpro inhibitors, leading to the identification of MG-101 as a competitive inhibitor, while confirming that several other compounds are ineffective.
Article Abstract
The outbreak of coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global threat to human health. In parallel with vaccines, efficacious antivirals are urgently needed. SARS-CoV-2 main protease (Mpro) is an attractive drug target for antiviral development owing to its key roles in virus replication and host immune evasion. Due to the limitations of currently available methods, the development of novel high-throughput screening assays is of the highest importance for the discovery of Mpro inhibitors. In this study, we first developed an improved fluorescence-based assay for rapid screening of Mpro inhibitors from an anti-infection compound library using a versatile dimerization-dependent red fluorescent protein (ddRFP) biosensor. Utilizing this assay, we identified MG-101 as a competitive Mpro inhibitor in vitro. Moreover, our results revealed that ensitrelvir is a potent Mpro inhibitor, but baicalein, chloroquine, ebselen, echinatin, and silibinin are not. Therefore, this robust ddRFP assay provides a faithful avenue for rapid screening and evaluation of Mpro inhibitors to fight against COVID-19.
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| http://dx.doi.org/10.1002/jmv.29498 | DOI Listing |
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