PXD075140-1

PXD075140 is an original dataset announced via ProteomeXchange.

Title	Human Angiotensin-Converting Enzyme 2-Specific Benzothiazole Allosteric Inhibitor against Pan-Sarbecoviruses
Description	Emerging SARS-CoV-2 variants of concern (VOCs) have demonstrated exceptional transmissibility and a strong dependence on the cellular receptor human angiotensin-converting enzyme 2 (hACE2). In this study, we present MB-32, a benzothiazole-based small molecule allosteric inhibitor of hACE2, which exhibits broad-spectrum antiviral activity against multiple SARS-CoV-2 VOCs, SARS-CoV-1, and bat/pangolin-derived sarbecoviruses. MB-32 effectively inhibits lung infections and prevents contact transmission of the SARS-CoV-2 Omicron in animal models. We subsequently studied the binding site of MB-32 on hACE2 using formaldehyde (FA) crosslinking coupled with mass spectrometry. To investigate FA crosslinking modifications, we utilized the mass of 558.22 Da, which is derived from the monoisotopic mass of MB-32 (534.22 Da) combined with a 2-carbon (24 Da) bridge, using PEAKS Studio 11. Focusing on four fixed amino acid type—saspartic acid, tyrosine, arginine, and lysine—we detected a 558.22 Da adduct in the combined mass of two peptides containing Y83 (EQSTLAQMY83PLQEIQNLTVK) and K94 (EQSTLAQMYPLQEIQNLTVK94), with high confidence scores of 1000.
HostingRepository	PRIDE
AnnounceDate	2026-05-01
AnnouncementXML	Submission_2026-05-01_02:10:27.859.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kong Hung SZE
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-03 05:19:51	ID requested
⏵ 1	2026-05-01 02:10:28	announced

Dataset with its publication pending

submitter keyword: Human, MB-32, entry inhibtor, Angiotensin-Converting Enzyme 2, COVID19, allosteric inhibitor, sarbecovirus, benzothiazole, Formaldehyde crosslinking

Dr. Liu Li
contact affiliation	Department of Microbiology, The University of Hong Kong, Hong Kong, SAR, China
contact email	liuli71@hku.hk
lab head
Kong Hung SZE
contact affiliation	Department of Microbiology, University of Hong Kong
contact email	konghungsze@gmail.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/2026/05/PXD075140

PRIDE project URI

• PRIDE
  1. PXD075140
     1. Label: PRIDE project
     2. Name: Human Angiotensin-Converting Enzyme 2-Specific Benzothiazole Allosteric Inhibitor against Pan-Sarbecoviruses