Mechanism-informed identification of FDA-approved topoisomerase inhibitors disrupting SARS-CoV-2 nucleocapsid-RNA interactions.

Da-Wei Zhang, Xiao-Shuang Xu, Lei Xu, Liangxu Xie, Yimin Li, Shan Chang

Abstract read

In one paragraph

Article in BMC chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

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1 · What the graph read from it

What it found

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Da-Wei ZhangInstitute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, 213001, China.

Xiao-Shuang XuInstitute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, 213001, China.

Lei XuInstitute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, 213001, China.

Liangxu XieInstitute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, 213001, China.

Yimin LiCollege of Pharmacy and Key Laboratory for Research and Development of ''Qin Medicine'' of Shaanxi Administration of Chinese Medicine, Shaanxi University of Chinese Medicine, Xixian New District, Xianyang, 712046, China. 2051058@sntcm.edu.cn.

Shan ChangInstitute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, 213001, China. schang@jsut.edu.cn.

Funding

Changzhou Sci. & Tech. Program CJ20200045Key Research and Development Program of Xianyang L2023-ZDYF-SF-017)National Natural Science Foundation of China 31700297

6 · The paper itself

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (NP) interaction with viral RNA is vital for viral replication and immune evasion, making it an attractive target for antiviral development. Inspired by adenosine triphosphate (ATP)'s competitive inhibition of NP-RNA binding, we screened 121 FDA-approved ATP-competitive kinase inhibitors, identifying mitoxantrone (IC₅₀ = 1.22 µM) as a potent inhibitor. Considering its known topoisomerase inhibitory activity, we further screened 23 additional topoisomerase inhibitors, uncovering four active compounds-pixantrone (IC₅₀ = 5.67 µM), doxorubicin (IC₅₀ = 20.19 µM), epirubicin (IC₅₀ = 7.23 µM), and suramin (IC₅₀ = 0.44 µM). Biolayer interferometry (BLI) revealed distinct inhibition mechanisms: suramin bound directly to the NP C-terminal domain (CTD) with a K

Indexed as

Biolayer interferometryDrug repurposingNucleocapsid proteinRNA–protein interaction inhibitorsSARS-CoV-2Topoisomerase inhibitors

Identifiers

PMID41299609

DOI10.1186/s13065-025-01689-7

PMCPMC12751893

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LicenceCC BY-NC-ND

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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.