Evidence map›Paper›PMID 40175846›Full record

ArticleMolecular diversity2026

Discovery and optimization of AAK1 inhibitors based on 1H-indazole scaffold for the potential treatment of SARS-CoV-2 infection.

Zi Hui, Haowen Deng, Yueying Xu, Yuan Gao, Chenfeng Zhai, Nian-Dong Mao, Hao Che, Zhen Li, Yuting Zhang, Hang Zhang and 2 more

Abstract read
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Article in Molecular diversity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Virus infection and vesicle trafficking.Frontiers in immunology · 2025
    Review
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

12 authors.

Zi Hui *School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, P. R. China.
Haowen Deng *School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, P. R. China.
Yueying XuSchool of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, P. R. China.
Yuan GaoClinical Medicine Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, 311121, Zhejiang, P. R. China.
Chenfeng ZhaiSchool of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, P. R. China.
Nian-Dong MaoSchool of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, P. R. China.
Hao CheSchool of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, P. R. China.
Zhen LiSanOmics AI Co. Ltd, Hangzhou, 3l1103, Zhejiang, P. R. China.
Yuting ZhangSchool of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, P. R. China.
Hang ZhangSchool of Basic Medical Science, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, P. R. China. 20090096@hznu.edu.cn.
Tian XieSchool of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, P. R. China. xbs@hznu.edu.cn.
Xiang-Yang YeSchool of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, P. R. China. xyye@hznu.edu.cn.ORCID https://orcid.org/0000-0003-3739-0930

Funding

National Natural Science Foundation of China 82073686
6 · The paper itself

Abstract

The process of various virus entry into host cells, including SARS-CoV-2, is mediated by clathrin-mediated endocytosis (CME). AP-2 plays a crucial role in this process by recognizing membrane receptors and binding with clathrin, facilitating the formation of clathrin-coated vesicles and promoting CME. AAK1 catalyzes the phosphorylation of AP2M1 subunit at Thr156. Therefore, suppressing AAK1 activity can hinder virus invasion by blocking CME. indicating that AAK1 could be a potential target for developing novel antiviral drugs against SARS-CoV-2. In this study, we present a series of novel AAK1 inhibitors based on previously reported AAK1 inhibitors. Drug design was carried out by fusing the 1H-indazole scaffold of SGC-AAK1-1 with pharmacophore groups of compound 6, and further optimized with the assistance of molecular docking. Among the 42 compounds novelly synthesized, compounds 9i, 9s, 11f and 11l exhibited comparable antiviral activity against SARS-CoV-2 infection compared to reference compound 6 at the concentration of 3 μM. Particularly, 11f showed almost no cytotoxicity at all tested concentrations. Additionally, 11f exhibited favorable predictive pharmacokinetic properties. These findings support the potential of 11f as a lead compound for developing antiviral drugs targeting SARS-CoV-2 infection, as well as potentially other viruses which are dependent on the CME process to enter host cells. In summary, we have expanded the structural types of AAK1 inhibitors and successfully obtained effective AAK1 inhibitors with antiviral capabilities.

Indexed as

Angiotensin-Converting Enzyme 2Antiviral AgentsCOVID-19 Drug TreatmentIndazolesProtein Kinase InhibitorsSARS-CoV-2AnimalsChlorocebus aethiopsCOVID-19Drug DiscoveryHumansMolecular Docking SimulationVero CellsVirus InternalizationAngiotensin-Converting Enzyme 2Antiviral AgentsIndazolesProtein Kinase Inhibitors1H-indazole scaffoldAAK1Drug designSARS-CoV-2 infection

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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.