Evidence map›Paper›PMID 41319177›Full record

ArticleChemistry (Weinheim an der Bergstrasse, Germany)2026

Tricarbonyl Rhenium-Based PROTACs Degrade the SARS-CoV-2 Mpro Protease.

Liuruiqi Luo, Yuxiang Lu, He Meng, Wenkai Lin, Kai Lu, Jing Wang, Jinghui Wang, Yufang Xiong, Zong-Wan Mao, Wei Xia

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Liuruiqi LuoMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry, Sun Yat-Sen University, Guangzhou, China.
Yuxiang LuMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry, Sun Yat-Sen University, Guangzhou, China.
He MengMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry, Sun Yat-Sen University, Guangzhou, China.
Wenkai LinMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry, Sun Yat-Sen University, Guangzhou, China.
Kai LuMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry, Sun Yat-Sen University, Guangzhou, China.
Jing WangMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry, Sun Yat-Sen University, Guangzhou, China.
Jinghui WangMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry, Sun Yat-Sen University, Guangzhou, China.
Yufang XiongMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry, Sun Yat-Sen University, Guangzhou, China.
Zong-Wan MaoMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry, Sun Yat-Sen University, Guangzhou, China.
Wei XiaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry, Sun Yat-Sen University, Guangzhou, China.ORCID https://orcid.org/0000-0001-6480-3265

Funding

National Natural Science Foundation of China 22077142
6 · The paper itself

Abstract

Targeted protein degradation (TPD) using proteolysis-targeting chimeras (PROTACs) offers advantages over occupancy-based inhibitors but faces challenges, including ligand discovery and cellular permeability. To address these limitations, we developed Re2, a metallo-PROTAC integrating a covalent rhenium(I) complex warhead targeting SARS-CoV-2 main protease (Mpro) Cys145 with the cereblon E3 ligase ligand pomalidomide. Re2 induced effective intracellular Mpro degradation at 100 nM within 72 h, which is significantly below its parent complex's enzymatic inhibition concentration. In vitro and ex vivo studies confirmed covalent Mpro binding and ubiquitin-proteasome system-dependent degradation. Crucially, Re2 exhibited three- to fourfold higher cellular uptake and greater intracellular accumulation than its demetallated organic counterpart, demonstrating that metalation overcomes intrinsic PROTAC permeability barriers. This work establishes metallo-PROTACs, exploiting the tunable coordination chemistry of metal complexes for enhanced target engagement and cellular delivery, as a potent strategy for designing high-potent PROTACs.

Indexed as

Coordination ComplexesCoronavirus 3C ProteasesRheniumSARS-CoV-2Antiviral AgentsHumansProteasome Endopeptidase ComplexProteolysisProteolysis Targeting ChimeraThalidomideUbiquitin-Protein Ligases3C-like proteinase, SARS-CoV-2Antiviral AgentsCoordination ComplexesCoronavirus 3C ProteasespomalidomideProteasome Endopeptidase ComplexProteolysis Targeting ChimeraRheniumThalidomideUbiquitin-Protein Ligasesmetal complexesPROTACprotein degradationSARS‐CoV‐2 main protease

Identifiers

PMID41319177
PMCPMC13451563

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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.