ArticleFrontiers in molecular biosciences2020
Insights Into Dynamics of Inhibitor and Ubiquitin-Like Protein Binding in SARS-CoV-2 Papain-Like Protease.
Article in Frontiers in molecular biosciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- A Review of In Silico Research, SARS-CoV-2, and Neurodegeneration: Focus on Papain-Like Protease.Neurotoxicity research · 2022Pooled it
- Computational Evaluation of Multitarget Capabilities of Phenylethanoid Glycosides Against SARS-CoV-2's 3CLPharmaceuticals (Basel, Switzerland) · 2026Article
- Structural analysis of the flexibility of the Ubl2 domain within the papain-like protease of SARS-CoV-2.Acta crystallographica. Section F, Structural biology communications · 2026Article
- Analysis of Structures of SARS-CoV-2 Papain-like Protease Bound with Ligands Unveils Structural Features for Inhibiting the Enzyme.Molecules (Basel, Switzerland) · 2025Review
- Viral deubiquitinating proteases and the promising strategies of their inhibition.Virus research · 2024Review
- Myrtucommulones and Related Acylphloroglucinols from Myrtaceae as a Promising Source of Multitarget SARS-CoV-2 Cycle Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Identification of Triazolopyrimidinyl Scaffold SARS-CoV-2 Papain-Like Protease (PLPharmaceutics · 2024Article
- Regulation of cGAS and STING signaling during inflammation and infection.The Journal of biological chemistry · 2023Review
- SARS-CoV-2 Papain-Like Protease: Structure, Function and Inhibition.Chembiochem : a European journal of chemical biology · 2022Review
- Parthenolide reveals an allosteric mode to inhibit the deISGylation activity of SARS-CoV‑2 papain-like protease.Acta biochimica et biophysica Sinica · 2022Article
- Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2.Chemical reviews · 2022Review
- Inhibitor induced conformational changes in SARS-COV-2 papain-like protease.Scientific reports · 2022Article
- Identification of bio-active food compounds as potential SARS-CoV-2 PLpro inhibitors-modulators via negative image-based screening and computational simulations.Computers in biology and medicine · 2022Article
- Identification of potent food constituents as SARS-CoV-2 papain-like protease modulators through advanced pharmacoinformatics approaches.Journal of molecular graphics & modelling · 2022Article
- Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease.Frontiers in chemistry · 2022Article
- COVID-19: A review of newly formed viral clades, pathophysiology, therapeutic strategies and current vaccination tasks.International journal of biological macromolecules · 2021Review
- Structure-Function Characteristics of SARS-CoV-2 Proteases and Their Potential Inhibitors from Microbial Sources.Microorganisms · 2021Review
- Article
- Non-Toxic Dimeric Peptides Derived from the Bothropstoxin-I Are Potent SARS-CoV-2 and Papain-like Protease Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- Inhibition of interferon-stimulated gene 15 and lysine 48-linked ubiquitin binding to the SARS-CoV-2 papain-like protease by small molecules:Chemical physics letters · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Covid-19 is caused by a novel form of coronavirus for which there are currently no vaccines or anti-viral drugs. This virus, termed SARS-CoV-2 (CoV2), contains Papain-like protease (PLpro) involved in viral replication and immune response evasion. Drugs targeting this protease therefore have great potential for inhibiting the virus, and have proven successful in older coronaviruses. Here, we introduce two effective inhibitors of SARS-CoV-1 (CoV1) and MERS-CoV to assess their potential for inhibiting CoV2 PLpro. We ran 1 μs molecular dynamics (MD) simulations of CoV2, CoV1, and MERS-CoV ligand-free PLpro to characterize the dynamics of CoV2 PLpro, and made comparisons between the three to elucidate important similarities and differences relevant to drug design and ubiquitin-like protein binding for deubiquitinating and deISGylating activity of CoV2. Next, we simulated the inhibitors bound to CoV1 and CoV2 PLpro in various poses and at different known binding sites to analyze their binding modes. We found that the naphthalene-based ligand shows strong potential as an inhibitor of CoV2 PLpro by binding at the putative naphthalene inhibitor binding site in both computational predictions and experimental assays. Our modeling work suggested strategies to improve naphthalene-based compounds, and our results from molecular docking showed that the newly designed compounds exhibited improved binding affinity. The other ligand, chemotherapy drug 6-mercaptopurine (6MP), showed little to no stable intermolecular interaction with PLpro and quickly dissociated or remained highly mobile. We demonstrate multiple ways to improve the binding affinity of the naphthalene-based inhibitor scaffold by engaging new residues in the unused space of the binding site. Analysis of CoV2 PLpro also brings insights into recognition of ubiquitin-like proteins that may alter innate immune response.
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Registered trials
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