ArticleAntiviral research2022
A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors.
Article in Antiviral research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Computational design of 3C-like protease substrate peptide for modular detection of protease activity of coronavirus.Engineering in life sciences · 2026Article
- A luminescent attenuated SARS-CoV-2 for the identification and validation of drug-resistant mutants.Journal of virology · 2025Article
- A light-resuming strategy as a screening method for selecting Sec61 inhibitors down-modulating PD-L1 expression.Nature communications · 2025Article
- Article
- Development of a highly sensitive luciferase assay for intracellular evaluation of coronavirus Mpro activity.Frontiers in microbiology · 2025Article
- Development of a reporter feline herpesvirus-1 for antiviral screening assays.Veterinary research · 2024Article
- An automated positive selection screen in yeast provides support for boron-containing compounds as inhibitors of SARS-CoV-2 main protease.Microbiology spectrum · 2024Article
- A Gaussia luciferase reporter assay for the evaluation of coronavirus Nsp5/3CLpro activity.Scientific reports · 2024Article
- Nonlinear Regression Modelling: A Primer with Applications and Caveats.Bulletin of mathematical biology · 2024Article
- Approved drugs successfully repurposed againstFrontiers in cellular and infection microbiology · 2024Article
- A community effort in SARS-CoV-2 drug discovery.Molecular informatics · 2024Article
- Broad antagonism of coronaviruses nsp5 to evade the host antiviral responses by cleaving POLDIP3.PLoS pathogens · 2023Article
- Design and synthesis of naturally-inspired SARS-CoV-2 inhibitors.RSC medicinal chemistry · 2023Article
- What do we know about the function of SARS-CoV-2 proteins?Frontiers in immunology · 2023Review
- Dual-Reporter System for Real-Time Monitoring of SARS-CoV-2 Main Protease Activity in Live Cells Enables Identification of an Allosteric Inhibition Path.ACS bio & med chem Au · 2022Article
- The development and characterization of a stable Coxsackievirus A16 infectious clone with Nanoluc reporter gene.Frontiers in microbiology · 2022Article
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17 authors at 3 institutions in 3 countries.
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Abstract
Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for the screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified two molecules which show anti-nsp5 activity, both in our cell-based assay and in vitro on purified nsp5 protein, and inhibit SARS-CoV-2 replication in A549-ACE2 cells with EC
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