Evidence map›Paper›PMID 33875421›Full record

ArticleAntimicrobial agents and chemotherapy2021

Structural Insights into the Mechanisms of Action of Functionally Distinct Classes of Chikungunya Virus Nonstructural Protein 1 Inhibitors.

Kristina Kovacikova, Marina Gorostiola González, Rhian Jones, Juan Reguera, Alba Gigante, María-Jesús Pérez-Pérez, Gerhard Pürstinger, Julia Moesslacher, Thierry Langer, Lak Shin Jeong and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
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

12 citing papers in PubMed, 17 citations in OpenAlex.

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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

15 authors at 8 institutions in 6 countries.

Kristina KovacikovaDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands.
Marina Gorostiola GonzálezDivision of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.
Rhian JonesAix-Marseille Université, INSERM, CNRS, AFMB UMR 7257, Marseille, France.
Juan RegueraAix-Marseille Université, INSERM, CNRS, AFMB UMR 7257, Marseille, France.
Alba GiganteInstituto de Química Médica (IQM-CSIC), Madrid, Spain.
María-Jesús Pérez-PérezInstituto de Química Médica (IQM-CSIC), Madrid, Spain.
Gerhard PürstingerDepartment of Pharmaceutical Chemistry, University of Innsbruck, Innsbruck, Austria.
Julia MoesslacherDepartment of Pharmacy, University of Innsbruck, Innsbruck, Austria.
Thierry LangerDepartment of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
Lak Shin JeongCollege of Pharmacy, Seoul National University, Seoul, South Korea.
Leen DelangKU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
Johan NeytsKU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
Eric J SnijderDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands.
Gerard J P van WestenDivision of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.
Martijn J van HemertDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands.
Leiden University Medical Center · NLCentre National de la Recherche Scientifique · FRInstituto de Química Médica · ESLeiden University · NLRega Institute for Medical Research · BEUniversität Innsbruck · ATSeoul National University · KRUniversity of Vienna · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chikungunya virus (CHIKV) nonstructural protein 1 (nsP1) harbors the methyltransferase (MTase) and guanylyltransferase (GTase) activities needed for viral RNA capping and represents a promising antiviral drug target. We compared the antiviral efficacies of nsP1 inhibitors belonging to the MADTP, CHVB, and FHNA series (6'-fluoro-homoneplanocin A [FHNA], its 3'-keto form, and 6'-β-fluoro-homoaristeromycin). Cell-based phenotypic cross-resistance assays revealed that the CHVB and MADTP series had similar modes of action that differed from that of the FHNA series. In biochemical assays with purified Semliki Forest virus and CHIKV nsP1, CHVB compounds strongly inhibited MTase and GTase activities, while MADTP-372 had a moderate inhibitory effect. FHNA did not directly inhibit the enzymatic activity of CHIKV nsP1. The first-of-their-kind molecular-docking studies with the cryo-electron microscopy (cryo-EM) structure of CHIKV nsP1, which is assembled into a dodecameric ring, revealed that the MADTP and CHVB series bind at the

Indexed as

Chikungunya virusViral Nonstructural ProteinsAdenosineCryoelectron MicroscopyMolecular Docking SimulationVirus Replication6'-beta-fluoro-homoaristeromycinAdenosineViral Nonstructural Proteinsantiviralsbinding pocketcappingChikungunya virusGTPinhibitorsmolecular dockingnsP1resistanceSAM

Identifiers

PMID33875421
PMCPMC8218635
OpenAlexW3154459164

What OpenQuestion holds

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LicenceCC BY
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 OpenQuestion graph.