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Respiratory Virus Infection
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Respiratory Virus Infection

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 20 January 2026 | Viewed by 2813

Special Issue Editor

Dr. Nikolaos Siafakas

E-Mail Website
Guest Editor
National and Kapodistrian University of Athens, School of Medicine, Clinical Microbiology Laboratory, ATTIKON University Hospital, Athens, Greece
Interests: molecular virology; COVID; SARS-CoV-2
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Respiratory virus infections are responsible for significant morbidity and mortality worldwide, with grave societal and economic consequences. The profound genetic plasticity of many respiratory viruses and their extremely high transmissibility have contributed to their perpetual evolutionary success and subsequent prevalence. The continuous emergence of novel variants of viruses like influenza and SARS-CoV-2 has caused devastating epidemics and pandemics. The constant surge in infections caused by other respiratory viruses has also imposed an additional, significant burden on societies and healthcare systems.

Therefore, efficient diagnosis, surveillance, and accurate characterization of novel variants with possibly increased virulence and epidemic potential are of critical importance. The limited therapeutic options and vaccines currently available also pose another significant challenge. There is an urgent need for further basic research on the various biological stages of the virus within the host and the pathophysiology that ensues in order to recognize potential therapeutic targets and design efficient antiviral drugs and vaccines.

This Special Issue of the International Journal of Molecular Sciences aspires to provide further insight into the challenges posed by respiratory virus infections in diagnosis, pathophysiology, epidemiology, and therapy, as well as to inform about the lessons that we have learnt from the recent, devastating epidemics.

Dr. Nikolaos Siafakas
Guest Editor

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Keywords

  • respiratory virus
  • diagnosis
  • surveillance
  • epidemiology
  • therapy
  • vaccination
  • influenza virus
  • coronavirus
  • respiratory syncytial virus
  • rhinovirus/enterovirus

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Published Papers (3 papers)

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Research

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22 pages, 7524 KiB  
Article
Role of Hypoxia-Inducible Factors in Respiratory Syncytial Virus Infection-Associated Lung Disease
by Dorothea R. Morris, Yue Qu, Aline Haas de Mello, Yava L. Jones-Hall, Tianshuang Liu, Meredith Weglarz, Teodora Ivanciuc, Roberto P. Garofalo and Antonella Casola
Int. J. Mol. Sci. 2025, 26(7), 3182; https://doi.org/10.3390/ijms26073182 - 29 Mar 2025
Viewed by 481
Abstract
Hypoxia-inducible factors (HIFs) are transcription factors that enable cells to adapt to low-oxygen environments. Viruses can exploit this pathway to enhance infection, making HIF modulation a potential antiviral strategy. In previous in vitro studies, we found that respiratory syncytial virus (RSV) stabilizes HIFs [...] Read more.
Hypoxia-inducible factors (HIFs) are transcription factors that enable cells to adapt to low-oxygen environments. Viruses can exploit this pathway to enhance infection, making HIF modulation a potential antiviral strategy. In previous in vitro studies, we found that respiratory syncytial virus (RSV) stabilizes HIFs under normoxic conditions with inhibition of HIF-1α reducing replication. Despite several HIF-modulating compounds being tested or approved in other non-infectious models, little is known about their efficacy against respiratory viruses in relevant animal models. This study aimed to characterize the disease-modulating properties and antiviral potential of HIF-1α (PX478) and HIF-2α PT2385 inhibitors in RSV-infected BALB/c mice. We found that the inhibition of HIF-1α worsened clinical disease parameters while simultaneously improving airway function. Blocking HIF-1α also significantly reduced peak RSV replication in the lung. In contrast, the inhibition of HIF-2α was associated with improved clinical parameters, no changes in airway function, and reduced viral replication following RSV infection. The analysis of lung cells found significant modification in the T-cell compartment that correlated with changes in lung pathology and viral titers for each HIF inhibitor. This study underscores the differential roles of HIF proteins in RSV infection and highlights the need for further characterization of compounds currently in use or under therapeutic consideration. Full article
(This article belongs to the Special Issue Respiratory Virus Infection)
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19 pages, 4617 KiB  
Article
Coumarins and Hesperetin Inhibit Human Respiratory Syncytial Virus Infection
by Jéssica Maróstica de Sá, Ilada Thongpan, Jefferson de Souza Busso, Thainá dos Santos Rodrigues, Phylip Chen, Alvaro Luiz Helena, Luis Octavio Regasini, Marcelo Andres Fossey, Ícaro Putinhon Caruso, Fátima Pereira de Souza and Mark Edward Peeples
Int. J. Mol. Sci. 2024, 25(24), 13301; https://doi.org/10.3390/ijms252413301 - 11 Dec 2024
Cited by 1 | Viewed by 1151
Abstract
Respiratory syncytial virus (RSV) is one of the most prevalent viruses that causes severe acute lower respiratory tract infections (ALRTIs) in the elderly and young children. There is no specific drug to treat RSV, only a broad-spectrum antiviral, ribavirin, which is only used [...] Read more.
Respiratory syncytial virus (RSV) is one of the most prevalent viruses that causes severe acute lower respiratory tract infections (ALRTIs) in the elderly and young children. There is no specific drug to treat RSV, only a broad-spectrum antiviral, ribavirin, which is only used in critical cases. Our research group is investigating antiviral agents of natural origin, such as coumarins and flavonoids, that may help reduce or prevent RSV infection. The cytotoxic concentrations of coumarins and hesperetin were tested on A549 and HEp-2 cells and used in inhibition tests in which 80% of the cells were viable. The anti-RSV action of the molecules was analyzed in A549 and HEp-2 cells and in HBE cell cultures infected with RSV-luc or rgRSV. We also encapsulated the compounds using β-cyclodextrin to improve the permeability and solubility of the molecules. Esculetin and 4-methyl inhibited rgRSV effectively on A549 and HEp-2 cells after 24 hpi, and when they were encapsulated, coumarin, esculetin, and hesperetin presented inhibition against rgRSV in HBE culture. The coumarins inhibit RSV replication in cell culture and even manage to overcome the mucus barriers of the HBE cultures, and β-cyclodextrin was essential for some of the coumarins to enter the cell and therefore to reach their targets. Full article
(This article belongs to the Special Issue Respiratory Virus Infection)
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Review

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15 pages, 1920 KiB  
Review
Challenges and Opportunities for Post-COVID Pulmonary Disease: A Focused Review of Immunomodulation
by Steffi Verbeeck Mendez, Isabella L. Do Orozco, Guadalupe E. Gavilanez-Chavez, Arnulfo Hernán Nava-Zavala and Maria G. Zavala-Cerna
Int. J. Mol. Sci. 2025, 26(8), 3850; https://doi.org/10.3390/ijms26083850 - 18 Apr 2025
Viewed by 467
Abstract
The resolution of the recent COVID-19 pandemic still requires attention, since the consequences of having suffered the infection, even in mild cases, are associated with several acute and chronic pathological conditions referred to as post-COVID syndrome (PCS). PCS often manifests with pulmonary disease [...] Read more.
The resolution of the recent COVID-19 pandemic still requires attention, since the consequences of having suffered the infection, even in mild cases, are associated with several acute and chronic pathological conditions referred to as post-COVID syndrome (PCS). PCS often manifests with pulmonary disease and, in up to 9% of cases, a more serious complication known as post-COVID-19 pulmonary fibrosis (PC19-PF), which has a similar clinical course as idiopathic pulmonary fibrosis (IPF). Generating knowledge to provide robust evidence about the clinical benefits of different therapeutic strategies to treat the pulmonary effects of PCS can provide new insights to amplify therapeutic options for these patients. We present evidence found after a scoping review, following extended PRIMSA guidelines, for the use of immunomodulators in pulmonary PCS. We start with a brief description of the immunomodulatory properties of the relevant drugs, their clinically proven efficacy for viral infections and chronic inflammatory conditions, and their use during the COVID-19 pandemic. We emphasize the need for well-designed clinical trials to improve our understanding the physiopathology of pulmonary PCS and PC19-PF and also to determine the efficacy and safety of candidate treatments. Full article
(This article belongs to the Special Issue Respiratory Virus Infection)
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