Evidence map›Paper›PMID 42179838›Full record

ArticleFrontiers in chemistry2026

Synthesis, structure-activity relationships, and SARS-CoV-2 antiviral activity of 3,5-disubstituted isothiazolo[4,3-

Ling-Jie Gao, Demian Kalebic, Chieh Wen Lo, Aakriti Gangwal, Do Hoang Nhu Tran, Jef Rozenski, Dominique Schols, Mathy Froeyen, Wim Dehaen, Shirit Einav and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in chemistry, 2026. 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.

Ling-Jie GaoLaboratory of Medicinal Chemistry, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
Demian KalebicSustainable Chemistry for Metals and Molecules, Department of Chemistry, KU Leuven, Leuven, Belgium.
Chieh Wen LoDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, United States.
Aakriti GangwalDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, United States.
Do Hoang Nhu TranDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, United States.
Jef RozenskiLaboratory of Medicinal Chemistry, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
Dominique ScholsMolecular, Structural and Translational Virology Research Group, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
Mathy FroeyenLaboratory of Medicinal Chemistry, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
Wim DehaenSustainable Chemistry for Metals and Molecules, Department of Chemistry, KU Leuven, Leuven, Belgium.
Shirit EinavDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, United States.
Steven De JongheMolecular, Structural and Translational Virology Research Group, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: 3-Alkynyl-6-aryl-isothiazolo[4,3-b]pyridines have previously been shown to be potent inhibitors of the lipid kinase FYVE finger-containing phosphoinositide kinase (PIKfyve), displaying broad-spectrum antiviral activity. Methods: To further study their structure-activity relationship (SAR), an efficient synthesis toward 3- bromo-5-chloro-isothiazolo[4,3-b]pyridine was established. It allowed to introduce structural modifications at positions 3 and 5 by palladium-catalyzed cross-coupling reactions and nucleophilic aromatic substitutions. Results and discussion: It led to the generation of a focused library of 3,5-disubstituted isothiazolo[4,3-b]pyridines. Several derivatives exhibited potent PIKfyve inhibition (in the low nM range) in a biochemical assay and antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (in the low μM range). To gain an insight in their binding mode, molecular modeling was applied, indicating that these 3,5- disubstituted isothiazolo[4,3-b]pyridines bind to the ATP-binding site of PIKfyve, although with a different binding mode from that of the 3,6- disubstituted isothiazolo[4,3-b]pyridines.

Indexed as

antiviralisothiazolo[4,3-b]pyridinePIKfyveSARS-CoV-2structure–activity relationship

Identifiers

PMID42179838
PMCPMC13194157

What OpenQuestion holds

Textmetadata
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.