Evidence map›Paper›PMID 40685447›Full record

ArticleScientific reports2025

Statine-based peptidomimetics as SARS-CoV-2 Papain-like protease inhibitors: in Silico and in vitro studies.

Raiane Dandara Pereira Pimentel, Priscila Goes Camargo, Pedro Henrique R de A Azevedo, Larissa Esteves Carvalho Constant, Stephany da Silva Costa, Diego Allonso, Carlos Rangel Rodrigues, Magaly Girão Albuquerque, Luiza R S Dias, Estela Maris F Muri and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Raiane Dandara Pereira PimentelFederal University of Rio de Janeiro, CCMN, Chemistry Institute, Postgraduate Program in Chemistry - PGQu, Rio de Janeiro, RJ, 21941-853, Brazil.ORCID http://orcid.org/0000-0002-6982-8215
Priscila Goes CamargoCCS, Pharmacy Faculty, Federal University of Rio de Janeiro, Rio de Janeiro, 21941- 853, RJ, Brazil.ORCID http://orcid.org/0000-0003-4483-2119
Pedro Henrique R de A AzevedoPharmacy Faculty, Medicinal Chemistry Laboratory, Fluminense Federal University, Niterói, 24241-000, RJ, Brazil.ORCID http://orcid.org/0000-0003-2512-5267
Larissa Esteves Carvalho ConstantDA - Laboratory of Biotechnology and Tissue Bioengineering, Federal University of Rio de Janeiro, LECC, SSC, Carlos Chagas Filho Biophysic Institute, CCS, Rio de Janeiro, 21941-902, RJ, Brazil.ORCID http://orcid.org/0000-0003-4011-8532
Stephany da Silva CostaDA - Laboratory of Biotechnology and Tissue Bioengineering, Federal University of Rio de Janeiro, LECC, SSC, Carlos Chagas Filho Biophysic Institute, CCS, Rio de Janeiro, 21941-902, RJ, Brazil.ORCID http://orcid.org/0009-0001-1041-5627
Diego AllonsoDA - Laboratory of Biotechnology and Tissue Bioengineering, Federal University of Rio de Janeiro, LECC, SSC, Carlos Chagas Filho Biophysic Institute, CCS, Rio de Janeiro, 21941-902, RJ, Brazil.ORCID http://orcid.org/0000-0002-1410-480X
Carlos Rangel RodriguesCCS, Pharmacy Faculty, Federal University of Rio de Janeiro, Rio de Janeiro, 21941- 853, RJ, Brazil.ORCID http://orcid.org/0000-0001-8453-7654
Magaly Girão AlbuquerqueFederal University of Rio de Janeiro, CCMN, Chemistry Institute, Postgraduate Program in Chemistry - PGQu, Rio de Janeiro, RJ, 21941-853, Brazil.ORCID http://orcid.org/0000-0003-1558-0928
Luiza R S DiasPharmacy Faculty, Medicinal Chemistry Laboratory, Fluminense Federal University, Niterói, 24241-000, RJ, Brazil.ORCID http://orcid.org/0000-0001-5809-5602
Estela Maris F MuriPharmacy Faculty, Medicinal Chemistry Laboratory, Fluminense Federal University, Niterói, 24241-000, RJ, Brazil.ORCID http://orcid.org/0000-0001-8489-1848
Camilo Henrique da Silva LimaFederal University of Rio de Janeiro, CCMN, Chemistry Institute, Postgraduate Program in Chemistry - PGQu, Rio de Janeiro, RJ, 21941-853, Brazil. camilolima@iq.ufrj.br.ORCID http://orcid.org/0000-0002-5579-7809

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 001Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro SEI-260003/019723/2022, SEI-260003/007043/2022, SEI-260003/003788/2022, E-26/210.403.2022, E-26/201.303/2022
6 · The paper itself

Abstract

We investigated statin-based peptidomimetic compounds as inhibitors of SARS-CoV-2 papain-like protease (PLpro) by in silico methods, including molecular docking/dynamic simulations and ADMET prediction, as well as enzymatic in vitro assays. Five compounds (LQMed 426, 428, 430, 431, and 432) were identified as having promising interactions with the active site and an allosteric site of PLpro. The docking poses in the active site revealed that the compounds interacted with the catalytic triad (Cys111, His272, and Asp286). Compound 426 stood out for forming significant hydrophobic interactions and hydrogen bonds. In molecular dynamic (MD) simulations, there was a tendency for the compounds to migrate to a pocket in the ubiquitin-like (Ubl) domain region, indicating possible allosteric inhibition. Principal component analysis (PCA) and free energy landscape (FEL) plot showed significant differences in the conformational stability of protein-ligand complexes. Complex 432 had the highest stability (PC1: 24.9%, PC2: 10.5%) with restricted movements, while complex 430 had the lowest stability and the highest PC1, indicating broader movements. Complexes 426 and 428 had intermediate stability. FEL analysis confirmed that complex 432 had multiple minimum energy clusters, suggesting a greater likelihood of stable enzyme-ligand complex. In vitro assays demonstrated that all compounds inhibited PLpro activity by at least 50%, with IC

Indexed as

Coronavirus 3C ProteasesPeptidomimeticsProtease InhibitorsSARS-CoV-2Antiviral AgentsCatalytic DomainCoronavirus Papain-Like ProteasesCOVID-19HumansMolecular Docking SimulationMolecular Dynamics SimulationAntiviral AgentsCoronavirus 3C ProteasesCoronavirus Papain-Like Proteasespapain-like protease, SARS-CoV-2PeptidomimeticsProtease InhibitorsCoViD-19InhibitorsMolecular DockingMolecular dynamicsPLproStatine

Identifiers

PMID40685447
PMCPMC12277432

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.