Search Results (1,450)

Background/Objectives: Viral respiratory infections have a significant impact on global health and the economy. While vaccines are effective in preventing infection, they might not be available or sufficient when used alone and must be complemented by specific therapeutic strategies. The development of new antiviral agents is increasingly important due to the continual emergence of novel respiratory pathogens. Previously we identified bovine lactoferrin (bLf)-derived tetrapeptides and peptidomimetics that showed potent in vitro activity against the influenza A virus in the picomolar range. Methods: Inspired by these results, in this study, we evaluated the antiviral potential of these compounds against HCoV-229E, a human coronavirus that can cause severe disease in immunocompromised individuals, using a compound repositioning approach. Results: Functional studies revealed that SK(N-Me)HS (3) interferes with viral entry and replication, while compound SNKHS (5) primarily blocks infection in the early stages. Biophysical analyses confirmed the occurrence of high-affinity binding to the viral spike protein, and computational studies suggested that the compounds target a region involved in conformational changes necessary for membrane fusion. Conclusions: These findings highlight these compounds as promising candidates for coronavirus entry inhibition and underscore the value of compound repurposing in antiviral development. Full article

Surveillance of swine influenza A virus (swIAV) traditionally focuses on respiratory matrices, yet emerging evidence suggests that fecal shedding and secondary environmental contamination may also contribute to viral dissemination. In this study, we collected and analyzed nasal, rectal, environmental, milk, and colostrum samples from naturally infected pigs in a commercial farm in Minas Gerais, Brazil. IAV RNA was detected in 25% of samples, including 42% from asymptomatic animals, with nasal swabs showing higher detection rates (30%) than rectal swabs (20%), though rectal Ct values were consistently higher, indicative of lower viral loads. We successfully isolated viable viruses from feces and effluent samples. Whole-genome sequencing revealed co-circulation of enzootic pH1N1 clade #2 (HA) and pN1 clade #4 (NA), alongside human-origin H3N2 sequences clustering within clade 3C.2a1b.2a.2a.1, and N2 segments related to pre-3C human lineages from 2001 to 2002. Phylogenetic and p-distance analyses support both recent reverse zoonosis and historical transmission events. Detection of complete HA/NA sequences from rectal swabs and treated effluent further emphasizes the surveillance value of non-respiratory matrices. The integration of respiratory and fecal/environmental sampling appears important to achieve more comprehensive IAV monitoring in swine herds and may have significant implications for One Health strategies in Brazil and beyond. Full article

Artificial intelligence (AI) techniques—ranging from hybrid mechanistic–machine learning (ML) ensembles to gradient-boosted decision trees, support-vector machines, and deep neural networks—are transforming the management of seasonal influenza, respiratory syncytial virus (RSV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptom-based triage models using eXtreme Gradient Boosting (XGBoost) and Random Forests, as well as imaging classifiers built on convolutional neural networks (CNNs), have improved diagnostic accuracy across respiratory infections. Transformer-based architectures and social media surveillance pipelines have enabled real-time monitoring of COVID-19. In HIV research, support-vector machines (SVMs), logistic regression, and deep neural network (DNN) frameworks advance viral-protein classification and drug-resistance mapping, accelerating antiviral and vaccine discovery. Despite these successes, persistent challenges remain—data heterogeneity, limited model interpretability, hallucinations in large language models (LLMs), and infrastructure gaps in low-resource settings. We recommend standardized open-access data pipelines and integration of explainable-AI methodologies to ensure safe, equitable deployment of AI-driven interventions in future viral-outbreak responses. Full article

Avian influenza viruses (AIVs) pose significant risks to occupational populations engaged in poultry farming, livestock handling, and live poultry market operations due to frequent exposure to infected animals and contaminated environments. This review synthesizes evidence on AIV exposure patterns and risk factors through a comprehensive analysis of viral characteristics, host dynamics, environmental influences, and human behaviors. The main routes of transmission include direct animal contact, respiratory contact during slaughter/milking, and environmental contamination (aerosols, raw milk, shared equipment). Risks increase as the virus adapts between species, survives longer in cold/wet conditions, and spreads through wild bird migration (long-distance transmission) and live bird trade (local transmission). Recommended control measures include integrated animal–human–environment surveillance, stringent biosecurity measures, vaccination, and education. These findings underscore the urgent need for global ‘One Health’ collaboration to assess risk and implement preventive measures against potentially pandemic strains of influenza A viruses, especially in light of undetected mild/asymptomatic cases and incomplete knowledge of viral evolution. Full article

Respiratory pathogens are significant causes of morbidity and mortality worldwide. Since the emergence of SARS-CoV-2 in 2019 and the mitigation measures implemented to control the pandemic, other respiratory viruses’ transmission and circulation patterns were substantially disrupted. We leveraged the influenza hospitalization surveillance in Tanzania to understand the distribution of respiratory viruses shortly after nonpharmaceutical interventions (NPIs) were lifted. A total of 475 samples that tested negative for SARS-CoV-2 and influenza from March through May 2022 were included in this study. The samples were tested for 16 virus targets using Anyplex II RV16 multiplex assays. The findings indicate that most hospitalizations (74%) were among children under 15 years, with human bocavirus (HBoV) being the most prevalent (26.8%), followed by rhinovirus (RV, 12.3%), parainfluenza viruses (PIVs1–4, 10.2%), respiratory syncytial virus (RSV, 8.7%), adenovirus (AdV, 4.3%), and metapneumovirus (MPV, 2.9%). Notably, 54% of respiratory hospitalizations had no viruses detected. The findings highlight the broad circulation of respiratory viruses shortly after NPIs were lifted in Tanzania. Surveillance for respiratory pathogens beyond influenza and SARS-CoV-2 can inform public health officials of emerging threats in the country and should be considered an important pandemic preparedness measure at a global level. Full article

The COVID-19 pandemic significantly impacted the circulation, seasonality, and disease burden of viral respiratory infections. This study aimed to evaluate the impact of SARS-CoV-2 on the frequency of viral respiratory infections at a teaching hospital in Southern Italy by comparing data from before, during, and after the COVID-19 pandemic and by investigating how the emergence of SARS-CoV-2 affected the circulation and seasonality of other respiratory viruses. This retrospective and prospective study was performed on de-identified nasopharyngeal specimens classified as pre-COVID-19 (before 15 March 2020), during-COVID-19 (from 16 March 2020 to 5 May 2023), and post-COVID-19 (from 6 May 2023 to 31 December 2024). Overall, 790 out of 3930 (20%) patient samples tested positive for at least one respiratory virus. The mean age of patients was 60 ± 19 years, with significant positivity rates observed in the 65–98 age group (p ≤ 0.05) across all periods. In the pre-COVID-19 period, the most prevalent virus was influenza A (47.5%, 47/99), followed by the human rhinovirus (19.2%, 19/99). During the COVID-19 pandemic, SARS-CoV-2 was the most prevalent (64.9%, 290/447), before decreasing to 38% (92/244) after the pandemic, while influenza A’s positivity prevalence increased to 14.3% (35/244). Rhinovirus/enterovirus remained relatively stable throughout all periods. The pandemic notably altered viral co-infection dynamics, with its effects lasting into the post-COVID-19 period. Specifically, a marked decrease in influenza A circulation was observed, while respiratory syncytial virus (RSV) epidemiology remained stable and significant co-circulation of rhinovirus/enterovirus with SARS-CoV-2 persisted. Therefore, since COVID-19 and influenza affect the same high-risk groups, those individuals must be vaccinated against both viruses. Full article

The scientific community’s interest in natural compounds with antiviral properties has considerably increased after the emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), especially for their potential use in the treatment of the COVID-19 infection. From this perspective, bovine coronavirus (BCoV), member of the genus β-CoV, represents a valuable virus model to study human β-CoVs, bypassing the risks of handling highly pathogenic and contagious viruses. Pimarane diterpenes are a significant group of secondary metabolites produced by phytopathogenic fungi, including several Diplodia species. Among the members of this class of natural products, sphaeropsidin A (SphA) and its analog sphaeropsidin B (SphB) are well known for their bioactivities, such as antimicrobial, insecticidal, herbicidal, and anticancer. In this study, the antiviral effects of SphA and SphB were evaluated for the first time on bovine (MDBK) cells infected with BCoV. Our findings showed that both sphaeropsidins significantly increased cell viability in infected cells. These substances also caused substantial declines in the virus yield and in the levels of the viral spike S protein. Interestingly, during the treatment, a cellular defense mechanism was detected in the downregulation of the aryl hydrocarbon receptor (AhR) signaling, which is affected by BCoV infection. We also observed that the presence of SphA and SphB determined the deacidification of the lysosomal environment in infected cells, which may be related to their antiviral activities. In addition, in silico investigations have been performed to elucidate the molecular mechanism governing the recognition of bovine AhR (bAhR) by Sphs. Molecular docking studies revealed significant insights into the structural determinants driving the bAhR binding by the examined compounds. Hence, in vitro and in silico results demonstrated that SphA and SphB are promising drug candidates for the development of efficient therapies able to fight a β-CoV-like BCoV during infection. Full article

Spores of filamentous fungi are common biological particles in indoor air that can negatively impact human health, particularly among immunocompromised individuals and patients with chronic respiratory conditions. Airborne viruses represent an equally pervasive threat, with some carrying the potential for pandemic spread, affecting both healthy individuals and the immunosuppressed alike. This study investigated the abundance and diversity of airborne fungal spores in both hospital and residential environments, using custom designed air samplers with or without the presence of negative air ions (NAIs) inside the sampler. The main purpose of investigation was the assessment of biological effects of NAIs on fungal spore viability, deposition, mycelial growth, and sporulation, as well as airborne viral load. The precise assessment of mentioned biological effects is otherwise difficult to carry out due to low concentrations of studied specimens; therefore, specially devised and designed, ion-bioaerosol interaction air samplers were used for prolonged collection of specimens of interest. The total fungal spore concentrations were quantified, and fungal isolates were identified using cultural and microscopic methods, complemented by MALDI-TOF mass spectrometry. Results indicated no significant difference in overall spore concentration between environments or treatments; however, presence of NAIs induced a delay in the sporulation process of Cladosporium herbarum, Aspergillus flavus, and Aspergillus niger within 72 h. These effects of NAIs are for the first time demonstrated in this work; most likely, they are mediated by oxidative stress mechanisms. A parallel experiment demonstrated a substantially reduced concentration of aerosolized equine herpesvirus 1 (EHV-1) DNA within 10–30 min of exposure to NAIs, with more than 98% genomic load reduction beyond natural decay. These new results on the NAIs interaction with a virus, as well as new findings regarding the fungal sporulation, resulted in part from a novel interaction setup designed for experiments with the bioaerosols. Our findings highlight the potential of NAIs as a possible approach for controlling fungal sporulation and reducing airborne viral particle quantities in indoor environments. Full article

Nipah virus (NiV) and Hendra virus (HeV), which both belong to the genus henipavirus, are zoonotic pathogens that cause severe systemic, neurological, and/or respiratory disease in humans and a variety of mammals. Therefore, monitoring viral prevalence in natural reservoirs and rapidly diagnosing cases of henipavirus infection are critical to limiting the spread of these viruses. Current laboratory methods for detecting NiV and HeV include virus isolation, reverse transcription quantitative real-time PCR (RT-qPCR), and antigen detection via an enzyme-linked immunosorbent assay (ELISA), all of which require highly trained personnel and specialized equipment. Here, we describe the development of a point-of-care customized immunochromatographic lateral flow (ILF) assay that uses recombinant human ephrin B2 as a capture ligand on the test line and a NiV-specific monoclonal antibody (mAb) on the conjugate pad to detect NiV and HeV. The ILF assay detects NiV and HeV with a diagnostic specificity of 94.4% and has no cross-reactivity with other viruses. This rapid test may be suitable for field testing and in countries with limited laboratory resources. Full article

While viral pathogens are often subdivided into neurotropic and non-neurotropic categories, systemic inflammation caused by non-neurotropic viruses still possesses the ability to alter the central nervous system (CNS). Studies of CNS disease induced by viral infection, whether neurotropic or not, are presented with a unique set of challenges. First, because brain biopsies are rarely necessary to diagnose viral-associated neurological disorders, antemortem tissue samples are not readily available for study and human pathological studies must rely on end-stage, postmortem evaluations. Second, in vitro models fail to fully capture the nuances of an intact immune system, necessitating the use of animal models to fully characterize pathogenesis and identify potential therapeutic approaches. Non-human primates (NHP) represent a particularly attractive animal model in that they overcome many of the limits posed by more distant species and most closely mirror human disease pathogenesis and susceptibility. Here, we review NHP infection models of viruses known to infect and/or replicate within cells of the CNS, including West Nile virus, the equine encephalitis viruses, Zika virus, and herpesviruses, as well as those known to alter the immune status of the brain in the absence of significant CNS penetrance, including human immunodeficiency virus (HIV) in the current era of combination antiretroviral therapy (cART) and the coronavirus of severe acute respiratory syndrome (SARS)-CoV−2. This review focuses on viruses with an established role in causing CNS disease, including encephalitis, meningitis, and myelitis and NHP models of viral infection that are directly translatable to the human condition through relevant routes of infection, comparable disease pathogenesis, and responses to therapeutic intervention. Full article

The broad-spectrum insect growth regulator (IGR) and insecticide 2-((1-(4-Phenoxyphenoxy)propan-2-yl)oxy)pyridine (MPEP; also known as pyriproxyfen) is increasingly being used to address public health programs for vector control, initiated by the spread of Zika virus in 2015–2016. While considered relatively safe for humans under normal conditions, limited toxicology data are available. Current studies were undertaken to address the data gap regarding potential immunotoxicity of MPEP, with particular emphasis on host resistance to viral infection. Hsd:Harlan Sprague Dawley SD^® rats were treated for 28 days by oral gavage with doses of 0, 62.5, 125, 250 or 500 mg/kg/day of MPEP in corn oil. There was a dose-dependent increase in liver weights which is consistent with the liver playing a dominant role in MPEP metabolism. However, no histological correlates were observed. Following treatment, rats were subjected to a battery of immune tests as well as an established rat model of influenza virus infection to provide a comprehensive assessment of immune function and host resistance. While several of the immune tests showed minor exposure-related changes, evidenced by negative dose–response trends, most did not show significant differences in any of the MPEP treatment groups relative to vehicle control. Most notable was a negative trend in pulmonary mononuclear cell phagocytosis with increases in dose of MPEP. There was also a positive trend in early humoral immune response (5 days after immunization) to keyhole limpet hemocyanin (KLH) as evidenced by increased serum anti-KLH IgM antibodies which was followed later (14 days following immunization) by decreasing trends in anti-KLH IgM and IgG antibody levels. However, MPEP treatment had no effect on the ability of rats to clear the influenza virus nor the T-dependent IgM and IgG antibody response to the virus. The lack of effects of MPEP on host resistance to influenza suggests the immune effects were minimal and unlikely to present a hazard with respect to susceptibility to respiratory viral infection. Full article

Inhaled corticosteroids (ICSs) are widely used to manage chronic respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), and human immunodeficiency virus (HIV). However, prolonged use of ICS is associated with the development of oropharyngeal candidiasis, a fungal infection primarily caused by Candida albicans, due to local immunosuppression in the oral cavity. The incidence of oropharyngeal candidiasis varies depending on geographic region, patient age, and comorbidities, with immunocompromised individuals, those with diabetes, and the elderly being particularly vulnerable. Key risk factors include high ICS doses, poor oral hygiene, and improper use of inhalers. Prevention is the cornerstone of managing oropharyngeal candidiasis associated with the chronic use of inhaled corticosteroids. Patient education on proper inhaler technique and oral hygiene is essential to reduce the risk of fungal overgrowth in the oral cavity. Additional preventive strategies include the use of spacers, mouth rinsing after inhalation, and proper denture care. In cases where these measures fail to prevent the infection, prompt detection and early intervention are crucial to prevent progression or recurrence. This narrative review aims to analyze the most effective prophylactic measures to prevent oropharyngeal candidiasis associated with the chronic use of inhaled corticosteroids, emphasizing patient education, oral hygiene, and proper use of inhalation devices. Full article

The recent global coronavirus pandemic highlighted the ever-present threat of respiratory virus outbreaks and the consequent need for ongoing research into antiviral therapy. To this end, structural analogues of the guanidinium-based drug camostat mesylate have been synthesised to probe their potential inhibition of Transmembrane Serine Protease 2 (TMPRSS2), a human protease that is essential for infection by many respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Our in vitro fluorescence-based protease assays and supporting computational docking studies suggest that C-terminal camostat analogues retain TMPRSS2 inhibition potencies (IC₅₀ = 1–3 nM, BE = −6.6 to −7.0 kcal/mol) that match or exceed that of the parent drug. Analogues 1c and 1d emerge as lead candidates in this regard, thereby validating the rationale behind C-terminal structural modifications and highlighting these derivatives as promising scaffolds for the future development of targeted antiviral therapeutics. Replacement of camostat’s ester functionality with peptide linkages largely preserves non-covalent binding but disrupts in vitro protease inhibition, findings consistent with the parent drug’s known role as an acylating suicide inhibitor. Docking studies confirm that the replacement of aromatic residues with flexible, equivalent-length alkyl chains is detrimental to drug binding. These function and binding data offer new directions for the synthesis of further analogues of camostat and of other guanidinium-based protease inhibitors that have yet to be refined via structure–activity relationship studies. Further investigation will support tailoring this class of drugs for repurposing in antiviral therapy. Full article

Macrophages are a principal pulmonary source of type I and III interferons (IFNs), initiating and coordinating the early antiviral response to respiratory viral infections. Yet the contribution of macrophage-derived IFNs to host defense during human metapneumovirus (HMPV) infection remains poorly defined. Here, we use human primary monocyte-derived macrophages (MDMs) and THP-1-derived macrophages to analyze the IFN responses induced by HMPV compared to its closely related human pneumovirus, respiratory syncytial virus (RSV). We show that HMPV induced a robust response of type I and type III IFNs and ISGs, whereas RSV elicited only a modest, delayed IFN response despite strong IRF activation; instead, RSV preferentially activates NF-κB and exhibits a pronounced proinflammatory cytokine output. Our results highlight the role of macrophages as key modulators of the IFN and proinflammatory responses during HMPV and RSV infection. Full article

Since 2020, the Gs/Gd H5N1 influenza virus (clade 2.3.4.4b) has established itself within wild bird populations across Asia, Europe, and the Americas, causing outbreaks in wild mammals, commercial poultry, and dairy farms. The impacts on the bird populations and the agricultural industry has been significant, requiring a One Health approach to enhanced surveillance in both humans and animals. To support pandemic preparedness efforts, we evaluated the Cepheid Xpert Xpress CoV-2/Flu/RSV plus kit and the BioFire Respiratory 2.1 Panel for their ability to detect the presence of non-seasonal, zoonotic influenza A viruses, including circulating H5N1 viruses from clade 2.3.4.4b. Both assays effectively detected the presence of influenza virus in clinically-contrived nasal swab and saliva specimens at low concentrations. The results generated using the Cepheid Xpert Xpress CoV-2/Flu/RSV plus kit and the BioFire Respiratory 2.1 Panel, in conjunction with clinical and epidemiological findings provide valuable diagnostic findings that can strengthen pandemic preparedness and surveillance initiatives. Full article