Evidence map›Paper›PMID 42107085›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

ZDHHC18-Mediated Palmitoylation of ORF3a Promotes SARS-CoV-2 Pathogenesis by Antagonizing TRIM16-Mediated Ubiquitination and Proteasomal Degradation.

Sidi Yang, Kun Li, Lihong Liu, Linsen Zeng, Qifeng Deng, Jiacheng Huang, Xiaoran Dong, Xin Wang, Jianwei Liang, Hongchao Liu and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 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. 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

18 authors.

Sidi YangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.ORCID https://orcid.org/0000-0003-0251-0162
Kun LiKey Laboratory of Tropical Disease Control of Ministry of Education, Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, P. R. China.
Lihong LiuState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
Linsen ZengState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
Qifeng DengMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, P. R. China.
Jiacheng HuangGuangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou, P. R. China.
Xiaoran DongGuangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou, P. R. China.
Xin WangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
Jianwei LiangGuangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou, P. R. China.
Hongchao LiuState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
Hong PengCentre for Infection and Immunity (CII), School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, P. R. China.
Yuxin LinState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
Xiaolu XieState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
Yuzhen YeState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
Tiefeng XuState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
Zhaohuan WangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
Chun-Mei LiCentre for Infection and Immunity (CII), School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, P. R. China.
Deyin GuoState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.

Funding

Guangdong Basic and Applied Basic Research Foundation 2023A1515110979Guangdong Basic and Applied Basic Research Foundation 2024A1515011305Guangdong Provincial Center for Disease Control and Prevention Supports Talent Projects 0720240122Major Project of Guangzhou National Laboratory GZNL2023A01008National Natural Science Foundation of China 32200109National Natural Science Foundation of China 32400118National Natural Science Foundation of China 82394461Young Scientists Program of Guangzhou Laboratory QNPG23-08
6 · The paper itself

Abstract

SARS-CoV-2 accessory protein ORF3a contributes to viral pathogenesis through membrane remodeling, immune evasion, and inflammation induction. However, the molecular mechanisms underlying ORF3a-mediated pathogenesis remain poorly characterized, and no therapeutic strategies targeting ORF3a currently exist. Here, we demonstrate that palmitoylation, a post-translational modification, governs ORF3a-mediated viral pathogenesis. Specifically, ORF3a undergoes ZDHHC18-mediated palmitoylation at evolutionarily conserved Cys130/Cys133 residues, which stabilizes the protein by masking an intrinsic proteasomal degradation signal. This palmitoylation competitively inhibits tripartite motif-containing 16 (TRIM16)-dependent K27-linked polyubiquitination, thereby preventing ORF3a degradation and enhancing viral replication and inflammatory responses. A designed ORF3a-mimicking palmitoylation-inhibitory peptide (OPIP) blocked ORF3a palmitoylation, promoted its degradation, and significantly reduced SARS-CoV-2 pathogenicity. Collectively, these findings establish ZDHHC18-mediated palmitoylation as a central regulator of ORF3a stability and virulence, revealing a potentially druggable axis for disrupting SARS-CoV-2 pathogenesis.

Indexed as

AcyltransferasesCOVID-19DNA-Binding ProteinsSARS-CoV-2Ubiquitin-Protein LigasesViroporin ProteinsAnimalsHEK293 CellsHumansLipoylationProteasome Endopeptidase ComplexProtein Processing, Post-TranslationalProteolysisUbiquitinationVirus ReplicationAcyltransferasesDNA-Binding ProteinsORF3a protein, SARS-CoV-2Proteasome Endopeptidase ComplexUbiquitin-Protein LigasesViroporin ProteinsORF3apalmitoylationSARS‐CoV‐2viral pathogenesis

Identifiers

PMID42107085
PMCPMC13335985

What OpenQuestion holds

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Registered trials

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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.