Evidence map›Paper›PMID 41115470›Full record

ArticleMolecular & cellular proteomics : MCP2025

Identification of Cathepsin L as the Molecular Target of Hydroxychloroquine With Chemical Proteomics.

Jin Shang, Bingjie Hu, Karen Ka-Yan Kung, Jiajun Jiang, Qi Zhang, Man-Kin Wong, Hin Chu, Qian Zhao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular & cellular proteomics : MCP, 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

8 authors.

Jin ShangState Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biological and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China; Department of Applied Biological and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China; Centre for Eye and Vision Research, Hong Kong SAR, China.
Bingjie HuState Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Karen Ka-Yan KungState Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biological and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Jiajun JiangState Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biological and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China; Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.
Qi ZhangState Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biological and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China; Centre for Eye and Vision Research, Hong Kong SAR, China.
Man-Kin WongState Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biological and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China; Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China. Electronic address: mankin.wong@polyu.edu.hk.
Hin ChuState Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. Electronic address: hinchu@hku.hk.
Qian ZhaoState Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biological and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China; Department of Applied Biological and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China; Centre for Eye and Vision Research, Hong Kong SAR, China. Electronic address: q.zhao@polyu.edu.hk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hydroxychloroquine (HCQ) and chloroquine have been utilized as antimalarial drugs for decades. Recently, these compounds were reported to inhibit various viruses utilizing the endosomal entry pathway. However, their direct molecular targets in host cells remain elusive. In this study, we developed a clickable photo-crosslinking probe in combination with proteomic approaches to identified cathepsin L (CTSL) as the binding target of HCQ. Extensive biochemical and in silico analyses were conducted to validate the HCQ-CTSL interactions. HCQ significantly inhibited the protease activity of CTSL and suppressed CTSL-dependent coronavirus entry in cells that support endosomal entry pathway. These findings not only reveal the underlying mechanism of how HCQ inhibits endosomal viral entry but also guide the rational use of HCQ against other emerging infectious agents.

Indexed as

Cathepsin LHydroxychloroquineProteomicsEndosomesHumansProtein BindingSARS-CoV-2Virus InternalizationCathepsin LCTSL protein, humanHydroxychloroquineantiviruscathepsin Lchemical proteomicshydroxychloroquinemolecular probe

Identifiers

PMID41115470
PMCPMC12719729

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.