Proteomics

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Zapnometinib treatment and influenza A virus infection induce alteration on the HLA class I ligandome of human lung adenocarcinoma cells

ABSTRACT: Targeting cellular factors is considered a promising approach to combat viral infection and overcome the resistance issue associated with direct-acting antiviral (DAA) drugs administration. In the context of drug repurposing strategies, we have previously explored the antiviral efficacy of the MEK inhibitor zapnometinib against influenza virus and SARS-CoV-2. Herein, since zapnometinib was originally promoted as an anti-cancer drug, we aimed to investigate the impact of zapnometinib on the HLA class I ligandome post-treatment and IAV infection. By implementing the immunopeptidomics approach, the influence on the HLA-I allotype distribution of the HLA ligands was observed to coincide with alteration in the relative abundance of HLA-I-presented peptides. Furthermore, functional annotation analysis of the corresponding source proteins of presented ligands revealed a remarkable gene enrichment of distinct cellular processes. Taken together, zapnometinib and IAV showed a remarkable effect on the HLA-I ligandome plasticity as well as quantitative alterations in HLA ligandome composition.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Influenza

SUBMITTER: Hazem Hamza Ewess  

LAB HEAD: Prof. Dr. Oliver Planz

PROVIDER: PXD041578 | Pride | 2026-06-15

REPOSITORIES: Pride

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Zapnometinib treatment and influenza A virus infection modulate the HLA class I ligandome in human lung adenocarcinoma cells.

Hamza Hazem H   Ghosh Michael M   Rammensee Hans-Georg HG   Planz Oliver O  

Frontiers in immunology 20260526

<h4>Introduction</h4>Influenza viruses continue to pose a global health threat, and available antiviral therapies are limited by resistance and reduced efficacy. Host-directed drugs such as MEK inhibitors have emerged as promising alternatives. Zapnometinib, a clinical-stage MEK inhibitor, has shown both antiviral and immunomodulatory activity. However, its impact on antigen presentation at the level of the HLA-I ligandome has not been investigated.<h4>Methods</h4>Label-free LC-MS/MS was applied  ...[more]

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