PXD010685

PXD010685 is an original dataset announced via ProteomeXchange.

Title	Receptor Tyrosine Kinase Inhibitors Block proliferation of coronavirus mainly through p38 mitogen-activated protein kinase pathways
Description	Emerging coronaviruses (CoVs) primarily cause severe gastroenteric or respiratory diseases in humans and animals, for which no approved therapeutics are available so far. Here A9, a receptor tyrosine kinase inhibitors (RTKIs) of the tyrphostin class was identified as a robust inhibitor of TGEV (Transmissible gastroenteritis virus) infection in cell-based assays. Time-of-addition studies suggested that A9 mainly acts at post-adsorption stage of the TGEV life cycle. Moreover, it also exhibited potent antiviral activity against various coronavirus replication, including MHV, PEDV and FIPV. We further investigated the mechanism of action of A9 against TGEV infection in vitro with comparative phosphoproteomics analysis. We specifically identified the A9 target, p38 and JNK1, the downstream molecules of receptor tyrosine kinases (RTKs) as required for efficient TGEV replication in vitro through plaque assay, qRT-PCR and western blotting assays. Additionally, tests of p38 and JNK1 inhibitors also indicated that interventions targeting p38 was more effective in suppressing TGEV propagation than the JNK. In conclusion, these findings indicate that the receptor tyrosine kinase inhibitor A9 can directly inhibits TGEV replication and its inhibitory activity on TGEV replication mainly regulated by targeting p38, which provide vital clues to design novel drugs against coronavirus.
HostingRepository	PRIDE
AnnounceDate	2020-05-26
AnnouncementXML	Submission_2020-05-26_12:02:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	xiaomei li
SpeciesList	scientific name: Sus scrofa (Pig); NCBI TaxID: 9823;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-08-06 02:54:27	ID requested
⏵ 1	2020-05-26 12:02:07	announced

Dong W, Xie W, Liu Y, Sui B, Zhang H, Liu L, Tan Y, Tong X, Fu ZF, Yin P, Fang L, Peng G, Receptor tyrosine kinase inhibitors block proliferation of TGEV mainly through p38 mitogen-activated protein kinase pathways. Antiviral Res, 173():104651(2020) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Emerging coronaviruses, RTKIs, Transmissible gastroenteritis virus, LC–MS/MS Analysis.

guiqing peng
contact affiliation	The State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China
contact email	penggq@mail.hzau.edu.cn
lab head
xiaomei li
contact affiliation	PTM Biolabs lnc.
contact email	xiaomei_li@ptm-biolab.com
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/2020/05/PXD010685

PRIDE project URI

• PRIDE
  1. PXD010685
     1. Label: PRIDE project
     2. Name: Receptor Tyrosine Kinase Inhibitors Block proliferation of coronavirus mainly through p38 mitogen-activated protein kinase pathways