PXD063557

PXD063557 is an original dataset announced via ProteomeXchange.

Title	Degraders of the dengue virus capsid protein exhibit differentiated pharmacology relative to capsid inhibitors
Description	Due to the limited size of viral genomes, most viral proteins are multifunctional; yet most direct-acting antivirals are designed as single-function inhibitors. The dengue virus (DENV) capsid protein serves as a building block for new virions while also interacting with multiple host factors to remodel the cellular environment. Using established capsid inhibitor ST148 as a targeting ligand, we developed a DENV capsid degrader, RPG-01-132, that exhibits a broadened spectrum of activity against the four DENV serotypes and a known ST148-resistant virus. Using multiple approaches, we show that RPG-01-132's sub-micromolar antiviral activity is due to CRL4CRBN-dependent degradation of capsid and that this mechanism both prevents formation of virions and blocks capsid's antagonism of the interferon response. This pharmacology is well-differentiated from ST148, which prevents virion budding but has no demonstrated effect on capsid's nonstructural functions. Targeted protein degradation can thus enable improved activity spectrum and new antiviral pharmacology.
HostingRepository	PRIDE
AnnounceDate	2026-03-30
AnnouncementXML	Submission_2026-03-29_17:28:47.387.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-02 06:23:25	ID requested
⏵ 1	2026-03-29 17:28:48	announced

10.1038/s41467-026-69263-w;

Chakravarty A, Wang LN, Golden RP, Li Z, Donovan KA, Afanzar O, Zhang Y, Fischer ES, Gray NS, Yang PL, Degraders of the dengue virus capsid protein exhibit differentiated pharmacology relative to capsid inhibitors. Nat Commun, 17(1):(2026) [pubmed]

submitter keyword: Degrader, dengue, capsin, virus, CRBN, chemical biology, PROTAC, ubiquitin

Eric Fischer
contact affiliation	Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
contact email	eric_fischer@dfci.harvard.edu
lab head
Eric Fischer
contact affiliation	Dana-Farber Cancer Institute
contact email	eric_fischer@dfci.harvard.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/2026/03/PXD063557

PRIDE project URI

• PRIDE
  1. PXD063557
     1. Label: PRIDE project
     2. Name: Degraders of the dengue virus capsid protein exhibit differentiated pharmacology relative to capsid inhibitors