Evidence map›Paper›PMID 37781611›Full record

ArticlebioRxiv : the preprint server for biology2023

Polymorphic Structure Determination of the Macrocyclic Drug Paritaprevir by MicroED.

G Bu, E Danelius, L H Wieske, T Gonen

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

G BuDepartment of Biological Chemistry, University of California Los Angeles, 615 Charles E.Young Drive South, Los Angeles, CA 90095, USA.
E DaneliusDepartment of Biological Chemistry, University of California Los Angeles, 615 Charles E.Young Drive South, Los Angeles, CA 90095, USA.
L H WieskeDepartment of Chemistry - BMC, Uppsala University, Husargatan 3, 75237 Uppsala, Sweden.
T GonenDepartment of Biological Chemistry, University of California Los Angeles, 615 Charles E.Young Drive South, Los Angeles, CA 90095, USA.

Funding

TRD4: Design and Engineering of MicroED hardware for nanocrystallization and time resolved studiesP41GM136508 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GONEN, TAMIR · 2020 to 2024
$7.6M
NIGMS NIH HHS P41 GM136508
6 · The paper itself

Abstract

Paritaprevir is an orally bioavailable, macrocyclic drug used for treating chronic Hepatitis C virus infection. Its structures had been elusive to the public until recently when one of the crystal forms was solved by MicroED. In this work, we report the MicroED structures of two distinct polymorphic crystal forms of paritaprevir from the same experiment. The different polymorphs show conformational changes in the macrocyclic core, as well as the cyclopropylsulfonamide and methylpyrazinamide substituents. Molecular docking shows that one of the conformations fits well into the active site pocket of the NS3/4A serine protease target, and can interact with the pocket and catalytic triad via hydrophobic interactions and hydrogen bonds. These results can provide further insight for optimization of the binding of acylsulfonamide inhibitors to the NS3/4A serine protease. In addition, this also demonstrate the opportunity of deriving different polymorphs and distinct macrocycle conformations from the same experiments using MicroED.

Indexed as

CryoEMHCV ProteaseMacrocyclesMicroEDMolecular ChameleonsPolymorphism

Identifiers

PMID37781611
PMCPMC10541134

What OpenQuestion holds

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Registered trials

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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.