PXD042352

PXD042352 is an original dataset announced via ProteomeXchange.

Title	Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics
Description	Targeted protein degradation (TPD), as exemplified by proteolysis-targeting chimera (PROTAC), is a prominent paradigm in drug discovery. In this study, we applied conventional and novel PROTAC approaches to develop broad-spectrum antivirals (targeting key host factors for many different viruses) and virus-specific antivirals (targeting unique viral proteins). With respect to host-directed antivirals, we identified a small molecule degrader, FM-74-103, with pan-antiviral activities, as shown by inhibiting both RNA and DNA viruses. FM-74-103 elicits the selective degradation of human GSPT1, a translation termination factor, which further shuts down translation initiation. With respect to virus-specific antivirals, we developed viral RNA oligonucleotide-based bifunctional molecules (Destroyers). We provided proof-ofprinciple that RNA mimics of viral promoter sequences can be used as molecular glues to recruit viral polymerase (vPOL) and target it for degradation. Collectively, this study shows that TPD can be exploited to rationally design and develop the next generations of antivirals.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_06:42:25.952.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeffrey Johnson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-18 22:05:50	ID requested
1	2023-06-15 10:43:50	announced
⏵ 2	2023-11-14 06:42:26	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: PROTAC

Influenza

SARS-CoV-2

CMV

GSPT1

Oligonucleotide

Antiviral Therapeutics

Jeffrey R Johnson
contact affiliation	Microbiology Department at the Icahn School of Medicine at Mount Sinai
contact email	jeffrey.johnson@mssm.edu
lab head
Jeffrey Johnson
contact affiliation	Icahn School of Medicine at Mount Sinai
contact email	jeffrey.johnson@mssm.edu
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/2023/06/PXD042352

PRIDE project URI

• PRIDE
  1. PXD042352
     1. Label: PRIDE project
     2. Name: Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics