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Molecular Mechanisms and Treatments Targeting Respiratory Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 26 January 2026 | Viewed by 353

Special Issue Editor


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Guest Editor
Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Innsbruck, Innsbruck, Austria
Interests: macrophage; COVID-19; monocyte

Special Issue Information

Dear Colleagues,

Respiratory diseases are common, diverse and responsible for a significant cause of illness and death resulting in one of the main causes of death. Beside acute respiratory diseases like infections with bacteria, virus or fungi, also chronic respiratory diseases such as COPD, asthma, cystic fibrosis or tumors can decrease the quality of life and may result in life-threating situations. Due to the constant exposure to the environment the respiratory tract is a great example how the innate immune system coordinates detection and defense of inhaled material. Nevertheless, many aspects of the host-pathogen interactions or the exact molecular mechanisms of these chronic respiratory diseases are still unknown. Due to the wide range of diseases the field also allows a broad scope of treatment options with diverse targeting points and application ways. New techniques like 3D cell culture further allow to study new aspects of respiratory diseases and the treatment of these in a more realistic in vivo-like approach. 

This special issue welcomes original research articels and reviews adressing new aspects of molecular mechanisms of respiratory diseases and their treatment.

Dr. Stefanie Dichtl
Guest Editor

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Keywords

  • respiratory diseases
  • respiratory infections
  • COPD
  • cystic fibrosis
  • lung tumor
  • therapy
 

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Published Papers (1 paper)

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Research

19 pages, 5363 KB  
Article
Human Small Airway Epithelia Reveal Dichloroacetate as a Broad-Spectrum Antiviral Against Respiratory Viruses
by Paula Martínez de Iturrate, Bruno Hernáez, Patricia de los Santos, Yolanda Sierra-Palomares, Alba García-Gómez, Alonso Sánchez-Cruz, Catalina Hernández-Sánchez, Luis Rivas, Margarita del Val and Eduardo Rial
Int. J. Mol. Sci. 2025, 26(20), 9853; https://doi.org/10.3390/ijms26209853 (registering DOI) - 10 Oct 2025
Viewed by 235
Abstract
Respiratory viral infections are a major cause of morbidity and mortality worldwide. The COVID-19 pandemic has evidenced the need for broad-spectrum antivirals and improved preclinical models that more accurately recapitulate human respiratory disease. These new strategies should also involve the search for drug [...] Read more.
Respiratory viral infections are a major cause of morbidity and mortality worldwide. The COVID-19 pandemic has evidenced the need for broad-spectrum antivirals and improved preclinical models that more accurately recapitulate human respiratory disease. These new strategies should also involve the search for drug targets in the infected cell that hamper the development of resistance and of potential efficacy against diverse viruses. Since many viruses reprogram cellular metabolism to support viral replication, we performed a comparative analysis of inhibitors targeting the PI3K/AKT/mTOR pathway, central to virus-induced metabolic adaptations, using MRC5 lung fibroblasts and Huh7 hepatoma cells. HCoV-229E infection in MRC5 cells caused the expected shift in the energy metabolism but the inhibitors had markedly different effects on the metabolic profile and antiviral activity in these two cell lines. Dichloroacetate (DCA), a clinically approved inhibitor of aerobic glycolysis, showed antiviral activity against HCoV-229E in MRC5 cells, but not in Huh7 cells, underscoring that the screening model is more critical than previously assumed. We further tested DCA in polarized human small airway epithelial cells cultured in air–liquid interface, a 3D model that mimics the human respiratory tract. DCA reduced the viral progeny of HCoV-229E, SARS-CoV-2, and respiratory syncytial virus by 2–3 orders of magnitude, even when administered after infection was established. Our work reinforces the need for advanced human preclinical screening models to identify antivirals that target host metabolic pathways frequently hijacked by respiratory viruses, and establishes DCA as a proof-of-concept candidate. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatments Targeting Respiratory Diseases)
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