The global scourge of COVID-19 is a serious threat to public health, but effective therapies remain very limited for this disease. Therefore, the discovery of novel antiviral agents is urgently needed to fight against COVID-19. In the lifecycle of SARS-CoV-2, the causing pathogen of COVID-19, papain-like protease (PLpro) is responsible for the cleavage of polyprotein into functional units as well as immune evasion of vaccines. Hence, PLpro has been regarded as an attractive target to develop antiviral agents. Herein, we first developed a robust and simple sandwich-like fluorescence polarization (FP) screening assay for the discovery of PLpro inhibitors, and identified anacardic acid as a novel competitive inhibitor against PLpro in vitro with an IC 50 value of 24.26 ± 0.4 μM. This reliable FP screening assay could provide a prospective avenue for rapid discovery of antiviral agents targeting PLpro in a large-scale screening.
Dandan Hu,Tianyu Zhan,Zhiyong Guo,Sui Wang,Yufang Hu
A novel dual-modality readout biosensing method is developed for Cu(II), coenzyme (CoA) and histone acetyltransferase (HAT) analysis based on an electrosynthesized tris(bipyridine)ruthenium(II)-functionalized metal-organic framework (Ru-MOF). In this protocol, the Ru-MOF with a delicate structure serves as both an electrochemiluminescent (ECL) and fluorescent (FL) probe. Interestingly, Cu(II) can hinder the two distinct processes favorably, thus realizing bidirectional detection of Cu(II) via an “on-off” method. Simultaneously, CoA, which contains a sulfhydryl group, can ignite a reverse “off-on” process due to the polymeric interaction of CoA and Cu(II) (2: 1). Similarly, abundant CoA molecules could also be generated regularly by a typical HAT p300-driven acetylation reaction, hence accomplishing HAT p300 activity analysis. Subsequently, an ingenious “on-off” route is exhibited again by the introduction of some small molecules (including anacardic acid and C646), which present an inhibiting effect on HAT p300 activity. Furthermore, quantitative analysis of Cu(II), CoA and HAT p300 (ECL/FL) is achieved brightly with detection limits of 0.19/0.76 nM, 1.3/6.5 nM and 1.5/8.8 nM, respectively. Ultimately, this two-channel biosensor with excellent analytical performance is applied successfully in real samples, demonstrating its potential use in bioanalysis.
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