Evidence map›Paper›PMID 37243192›Full record

ArticleViruses2023

Allosteric Inhibitors of Zika Virus NS2B-NS3 Protease Targeting Protease in "Super-Open" Conformation.

Ittipat Meewan, Sergey A Shiryaev, Julius Kattoula, Chun-Teng Huang, Vivian Lin, Chiao-Han Chuang, Alexey V Terskikh, Ruben Abagyan

Abstract read
In one paragraph

Article in Viruses, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–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

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  3. Review
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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

8 authors.

Ittipat MeewanInstitute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand.
Sergey A ShiryaevSanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Julius KattoulaSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Chun-Teng HuangSanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Vivian LinSanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.ORCID 0000-0001-5886-1047
Chiao-Han ChuangSanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Alexey V TerskikhSanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.ORCID 0000-0003-4641-3997
Ruben AbagyanSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
Brain pathology and function in a chronic mouse model of ZIKV transmissionR01NS105969 · NINDS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MUOTRI, ALYSSON R., OLSON, STEVEN H · 2019 to 2023
$3.3M
Addressing biomedical challenges with computational mechanics and big dataR35GM131881 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ABAGYAN, RUBEN · 2019 to 2023
$1.9M
NCI NIH HHS P30 CA030199NIGMS NIH HHS R35 GM131881NIH HHS R01 NS105969-01NIH HHS R35GM131881
6 · The paper itself

Abstract

The Zika virus (ZIKV), a member of the Flaviviridae family, is considered a major health threat causing multiple cases of microcephaly in newborns and Guillain-Barré syndrome in adults. In this study, we targeted a transient, deep, and hydrophobic pocket of the "super-open" conformation of ZIKV NS2B-NS3 protease to overcome the limitations of the active site pocket. After virtual docking screening of approximately seven million compounds against the novel allosteric site, we selected the top six candidates and assessed them in enzymatic assays. Six candidates inhibited ZIKV NS2B-NS3 protease proteolytic activity at low micromolar concentrations. These six compounds, targeting the selected protease pocket conserved in ZIKV, serve as unique drug candidates and open new opportunities for possible treatment against several flavivirus infections.

Indexed as

Zika VirusZika Virus InfectionHumansInfant, NewbornPeptide HydrolasesProtease InhibitorsProtein ConformationSerine EndopeptidasesViral Nonstructural ProteinsPeptide HydrolasesProtease InhibitorsSerine EndopeptidasesViral Nonstructural Proteinsallosteric inhibitorssuper-open conformationZika virus NS2B-NS3 proteaseZika virus protease inhibitors

Identifiers

PMID37243192
PMCPMC10224173

What OpenQuestion holds

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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.