PXD031993

PXD031993 is an original dataset announced via ProteomeXchange.

Title	An anti-influenza A virus microbial metabolite acts by degrading viral endonuclease PA
Description	The emergence of new highly pathogenic and drug-resistant influenza strains urges the development of novel therapeutics for influenza A virus (IAV). Here, we report the discovery of an anti-IAV microbial metabolite called APL-16-5 that was originally isolated from the plant endophytic fungus Aspergillus sp. CPCC 400735. APL-16-5 binds to both the E3 ligase TRIM25 and IAV polymerase subunit PA, leading to TRIM25 ubiquitination of PA and subsequent degradation of PA in the proteasome. This mode of action conforms to that of a proteolysis targeting chimera which employs the cellular ubiquitin-proteasome machinery to chemically induce the degradation of target proteins. Importantly, APL-16-5 potently inhibits IAV and protects mice from lethal IAV infection. Therefore, we have identified a natural microbial metabolite with potent in vivo anti-IAV activity and the potential of becoming a new IAV therapeutic. The antiviral mechanism of APL-16-5 opens the possibility of improving its anti-IAV potency and specificity by adjusting its affinity for TRIM25 and viral PA protein through medicinal chemistry.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-20_08:37:35.267.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jianyuan Zhao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-02 01:35:26	ID requested
⏵ 1	2022-05-20 08:37:36	announced

Zhao J, Wang J, Pang X, Liu Z, Li Q, Yi D, Zhang Y, Fang X, Zhang T, Zhou R, Zhang T, Guo Z, Liu W, Li X, Liang C, Deng T, Guo F, Yu L, Cen S, An anti-influenza A virus microbial metabolite acts by degrading viral endonuclease PA. Nat Commun, 13(1):2079(2022) [pubmed]

submitter keyword: Influenza A virus

Proteolysis-targeting chimeras

TRIM25

phenalenone derivatives

microbial metabolites

antiviral drug

Shan Cen
contact affiliation	Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School
contact email	shancen@imb.pumc.edu.cn
lab head
Jianyuan Zhao
contact affiliation	Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School
contact email	zhaojianyuan@imb.pumc.edu.cn
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/05/PXD031993

PRIDE project URI

• PRIDE
  1. PXD031993
     1. Label: PRIDE project
     2. Name: An anti-influenza A virus microbial metabolite acts by degrading viral endonuclease PA