Search Results (2,532)

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

Background: Since the COVID-19 pandemic, managing acute infections in symptomatic individuals, regardless of vaccination status, has been widely debated and extensively studied. Even more concerning, however, is the impact of COVID-19 on pregnant women—especially its effects on fetuses and newborns. Several studies have documented complications in both expectant mothers and their infants following infection. Methods: In our previous works, we provided scientific evidence of the bacteriophage behavior of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). This demonstrated that a well-defined combination of two antibiotics, amoxicillin and rifaximin, is associated with the same statistics for subjects affected by severe cases of SARS-CoV-2, regardless of vaccination status. We considered the few cases in the literature regarding the management of pregnancies infected with SARS-CoV-2, as well as previous data published in our works. In this brief case series, we present two pregnancies from the same unvaccinated mother—one prior to the COVID-19 pandemic and the other during the spread of the Omicron variant—as well as one pregnancy from a mother vaccinated against COVID-19. We describe the management of acute maternal infection using a previously published protocol that addresses the bacteriophage and toxicological mechanisms associated with SARS-CoV-2. Results: The three pregnancies are compared based on fetal growth and ultrasound findings. This report highlights that, even in unvaccinated mothers, timely and well-guided management of symptomatic COVID-19 can result in positive outcomes. In all cases, intrauterine growth remained within excellent percentiles, and the births resulted in optimal APGAR scores. Conclusions: This demonstrates that a careful and strategic approach, guided by ultrasound controls, can support healthy pregnancies during SARS-CoV-2 infection, regardless of vaccination status. 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

Enteric diseases represent one of the main causes of morbidity and mortality in poultry production, especially in turkeys (Meleagris gallopavo), significantly affecting the profitability of the sector. Turkey enteric complex (PEC) is a multifactorial syndrome characterized by diarrhea, stunting, poor feed conversion, and increased mortality in young turkeys. Its aetiologia includes multiple avian enteric viruses, including astrovirus, rotavirus, reovirus, parvovirus, adenovirus, and coronavirus, which can act singly or in co-infection, increasing clinical severity. This study performs a systematic review of the literature on these viruses and a meta-analysis of their prevalence in different regions of the world. Phylogenetic analyses were used to assess the genetic diversity of the main viruses and their geographical distribution. The results show a wide regional and genetic variability, which underlines the need for continuous epidemiological surveillance. Health and production implications are discussed, proposing control strategies based on biosecurity, targeted vaccination, and optimized nutrition. These findings highlight the importance of integrated management to mitigate the impact of CSF in poultry. Full article

COVID-19 vaccine hesitancy in Pakistan is a barrier to optimal vaccine uptake and has been situated within a context of hesitancy towards other vaccines. A mixed-methods study was conducted during the initial COVID-19 vaccine roll-out in 2021 in four union councils in Peshawar, consisting of a cross-sectional survey, eight focus group discussions (FGDs) with community members and eight in-depth interviews with healthcare workers (HCWs) to assess perceptions toward vaccines. Multivariable logistic regression was used to assess factors associated with COVID-19 vaccine hesitancy. Of 400 survey participants, 57.3% were vaccine acceptant and 42.8% vaccine hesitant. Just over half (56.8%) perceived COVID-19 vaccines to be safe. Most (88%) reported trust in HCWs to provide accurate vaccine information. FGDs revealed that women received less information about the vaccine compared to men and cultural restrictions were barriers even for those willing to be vaccinated. Correlates of vaccine acceptance included male sex (aOR 2.25; 95% CI 1.29–3.91), age 50 years or greater (aOR 1.74; 95% CI 1.19–6.31), social network support (e.g., vaccine acceptance among an individual’s social network) in receiving COVID-19 vaccines (aOR 2.38; 95% CI 1.45–3.89), community concern about COVID-19 spread (aOR 2.84; 95% CI 1.73–4.66), and trust in HCWs to provide vaccine information (aOR 3.47; 95% CI 1.62–7.42). Future vaccine promotion should prioritize engaging community leaders, sharing transparent information, combatting misinformation and rumors, and implementing household-based interventions especially targeting the importance of vaccination among women and young people to increase uptake. Full article

Background: Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder characterized by bone fragility, most often caused by pathogenic variants in type I collagen genes. In this context, we aimed to describe the clinical and epidemiological characteristics of patients with OI who were hospitalized for coronavirus disease (COVID)-19 in Brazil between 2020 and 2024. Methods: We conducted a retrospective descriptive analysis using data from the Brazilian Unified Health System (SUS, which stands for the Portuguese Sistema Único de Saúde) through the Open-Data-SUS platform. Patients with a confirmed diagnosis of OI and hospitalization due to COVID-19 were included. Descriptive statistical analysis was performed to evaluate demographic, clinical, and outcome-related variables. We included all hospitalized COVID-19 cases with a confirmed diagnosis of OI between 2020 and 2024. Results: Thirteen hospitalized patients with OI and COVID-19 were identified. Most were adults (9; 69.2%), male (7; 53.8%), self-identified as White (9; 69.2%), and all were residents of urban areas (13; 100.0%). The most frequent symptoms were fever (10; 76.9%), cough (9; 69.2%), oxygen desaturation (9; 69.2%), dyspnea (8; 61.5%), and respiratory distress (7; 53.8%). Two patients had heart disease, one had chronic lung disease, and one was obese. As for vaccination status, five patients (38.5%) had been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Four patients (30.8%) required admission to an intensive care unit (ICU), and six (46.2%) required noninvasive ventilatory support. Among those admitted to the ICU, only two required invasive mechanical ventilation. The clinical outcome was death in two cases (15.4%). Both patients were male, White, and had not been vaccinated against SARS-CoV-2. One was 47 years old, was not admitted to the ICU, but required noninvasive ventilation. Despite the underlying condition most patients had favorable outcomes, consistent with an international report. Conclusions: This is the first report to describe the clinical and epidemiological profile of patients with OI hospitalized for COVID-19 in Brazil, providing initial insights into how a rare bone disorder intersects with an acute respiratory infection. The generally favorable outcomes observed—despite the underlying skeletal fragility—suggest that individuals with OI are not necessarily at disproportionate risk of severe COVID-19, particularly when appropriately monitored. The occurrence of deaths only among unvaccinated patients underscores the critical role of SARS-CoV-2 vaccination in this population. Although pharmacological treatment data were unavailable, the potential protective effects of bisphosphonates and vitamin D merit further exploration. These findings support the need for early preventive strategies, systematic vaccination efforts, and dedicated clinical protocols for rare disease populations during infectious disease outbreaks. Full article

Background: Kidney transplant recipients (KTRs) exhibit a significantly diminished immune response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccines compared with the general population, primarily due to ongoing immunosuppressive therapy. This study evaluated the immunogenicity of a third SARS-CoV-2 mRNA vaccine dose in KTRs and assessed the association between antibody response and protection against SARS-CoV-2 breakthrough infection. Additionally, the clinical and immunological correlates of post-vaccination SARS-CoV-2 infection were examined. Methods: A prospective cohort of 135 KTRs received a third vaccine dose approximately six months following the second dose. Plasma samples were collected at baseline (pre-vaccination), six months after the second dose, and six weeks following the third dose. Humoral responses were assessed using SARS-CoV-2-specific Immunoglobulin G (IgG) titers and virus neutralization assays against wild-type (WT) and viral strains, including multiple Omicron sub-lineages. Results: After the third vaccine dose, 74% of the KTRs had detectable SARS-CoV-2-specific IgG antibodies, compared with 48% following the second dose. The mean IgG titers increased approximately ten-fold post-booster. Despite this increase, neutralizing activity against the Omicron variants remained significantly lower than that against the WT strain. KTRs who subsequently experienced a SARS-CoV-2 breakthrough infection demonstrated reduced neutralizing antibody activity across all variants tested. Additionally, individuals receiving triple immunosuppressive therapy had a significantly higher risk of SARS-CoV-2 breakthrough infection compared with those on dual or monotherapy. A multivariate machine learning analysis identified age and neutralizing activity against WT, Delta, and Omicron BA.2 as the most robust correlates of SARS-CoV-2 breakthrough infection. Conclusions: A third SARS-CoV-2 mRNA vaccine dose significantly improves SARS-CoV-2-specific IgG levels in KTRs; however, the neutralizing response against Omicron variants remains suboptimal. Diminished neutralizing capacity and intensified immunosuppression are key determinants of SARS-CoV-2 breakthrough infection in this immunocompromised population. Full article

The emergence of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus closely related to SARS-CoV and officially known as Betacoronavirus pandemicum precipitated a substantial surge in vaccine development that culminated during the global COVID-19 pandemic. At present, there are dozens of vaccines for the prevention of SARS-CoV-2 being utilized across the globe. However, only 10 of these vaccines have been authorized by the World Health Organization (WHO). These include mRNA-based, viral vector, subunit and whole-virion inactivated vaccines. At the current end of the pandemic, there has been a decline in the global vaccination rate, both for the general population and for those most at risk of severe illness from the virus. This suggests that the effectiveness of the vaccines may be waning. The decline occurs alongside a decrease in testing and sequencing for SARS-CoV-2. Furthermore, the process of tracking viruses becomes increasingly complex, thereby providing a selective advantage for SARS-CoV-2 and allowing it to evolve stealthily. In this review, we provide a comprehensive overview of viral evolution and vaccine development. We also discuss ways to overcome viral variability and test universal vaccines for all SARS-CoV-2 variants. Full article

Coronavirus disease 2019 (COVID-19) produced devastating health and economic impacts worldwide. While progress has been made in vaccine development, effective antiviral treatments remain limited, particularly those targeting the papain-like protease (PLpro) of SARS-CoV-2. PLpro plays a key role in viral replication and immune evasion, making it an attractive yet underexplored target for drug repurposing. In this study, we combined machine learning, molecular dynamics, and molecular docking to identify potential PLpro inhibitors in existing drugs. We performed long-timescale molecular dynamics simulations on PLpro–ligand complexes at two known binding sites, followed by structural clustering to capture representative structures. These were used for molecular docking, including a training set of 127 compounds and a library of 1107 FDA-approved drugs. A random forest model, trained on the docking scores of the representative conformations, yielded 76.4% accuracy via leave-one-out cross-validation. Applying the model to the drug library and filtering results based on prediction confidence and the applicability domain, we identified five drugs as promising candidates for repurposing for COVID-19 treatment. Our findings demonstrate the power of integrating computational modeling with machine learning to accelerate drug repurposing against emerging viral targets. Full article

Despite current vaccines and therapeutics targeting SARS-CoV-2, the causative agent of the COVID-19 pandemic, cases remain high causing a burden on health care systems. Spike-protein mediated membrane fusion of SARS-CoV-2 is a critical step in viral entry. Herein, we describe entry inhibitors identified by first screening a library of about 160 compounds and then analogue synthesis. Specifically, compound 261 was found to inhibit SARS-CoV-2 infection in a tissue model with IC₅₀ of 0.3 µM. Using NMR, we found that 261 interacts with key residues in the aromatic-rich region of the spike protein directly next to the transmembrane domain. Molecular dynamic simulations of the 261 binding pocket in the spike protein was also mapped to the transmembrane domain, consistent with NMR findings. The amino acids in the binding site are conserved among different coronaviruses known to infect humans; therefore, inhibitors targeting this conserved binding site could be a useful addition to current therapeutics and may have pan-coronavirus antiviral activities. Full article

Background: Feline infectious peritonitis (FIP) is a complex and devastating viral disease in cats caused by feline coronavirus (FCoV). While FCoV is commonly encountered and typically innocuous, the emergence of a mutated variant can lead to the development of FIP, a severe and often fatal condition. Method and Results: This review article provides a comprehensive overview of the etiological factors, epidemiology, clinical manifestations, and challenges associated with FIP. Additionally, it underscores the critical need for further research to enhance diagnostic capabilities and develop effective therapeutic interventions. Conclusion: By shedding light on the intricate dynamics of FIP, this review paper aims to contribute to a deeper understanding of the disease via fostering therapeutic advancements that can improve outcomes for afflicted felines. Full article

The coronavirus disease 2019 (COVID-19) pandemic has led to substantial health and financial burdens worldwide, and vaccines provide hope for reducing the burden of this pandemic. However, vaccinated people remain at risk for SARS-CoV-2 infection. Genome-wide association studies (GWASs) may identify potential genetic factors involved in the development of COVID-19 breakthrough infections (BIs); however, very few or no GWASs have been conducted for COVID-19 BI thus far. We conducted a GWAS and detailed bioinformatics analysis on COVID-19 BIs in a European population via the UK Biobank (UKBB). We conducted a series of analyses at different levels, including SNP-based, gene-based, pathway, and transcriptome-wide association analyses, to investigate genetic factors associated with COVID-19 BIs and hospitalized infections. The polygenic risk score (PRS) and Hoeffding’s test were performed to reveal the genetic relationships between BIs and other medical conditions. Two independent loci (LD-clumped at r² = 0.01) reached genome-wide significance (p < 5 × 10⁻⁸), including rs36170929, which mapped to LOC102725191/VWDE, and rs28645263, which mapped to RETREG1. A pathway enrichment analysis highlighted pathways such as viral myocarditis, Rho-selective guanine exchange factor AKAP13 signaling, and lipid metabolism. The PRS analyses revealed significant genetic overlap between COVID-19 BIs and heart failure and between HbA1c and type 1 diabetes. Genetic dependence was also observed between COVID-19 BIs and asthma, lung abnormalities, schizophrenia, and type 1 diabetes on the basis of Hoeffding’s test. This GWAS revealed two significant loci that may be associated with COVID-19 BIs and a number of genes and pathways that may be involved in BIs. Genetic overlap with other diseases was identified. Further studies are warranted to replicate these findings and elucidate the mechanisms involved. Full article

Background: Vaccines represent one of the most affordable and efficient tools for controlling infectious diseases; however, the development of efficacious vaccines against complex pathogens remains a major challenge. Adjuvants play a relevant role in enhancing vaccine-induced immune responses. One such molecule is interferon-stimulated gene 15 (ISG15), a key modulator of antiviral immunity that acts both through ISGylation-dependent mechanisms and as a cytokine-like molecule. Methods: In this study, we assessed the immunostimulatory potential of ISG15 as an adjuvant in Modified Vaccinia virus Ankara (MVA)-based vaccine candidates targeting Zika virus (ZIKV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Early innate responses and immune cell infiltration were analyzed in immunized mice by flow cytometry and cytokine profiling. To elucidate the underlying mechanism of action of ISG15, in vitro co-infection studies were performed in macrophages. Finally, we evaluated the magnitude and functional quality of the elicited antigen-specific cellular immune responses in vivo. Results: Analysis of early innate responses revealed both platform- and variant-specific effects. ISG15AA preferentially promoted natural killer (NK) cell recruitment at the injection site, whereas ISG15GG enhanced myeloid cell infiltration in draining lymph nodes (DLNs), particularly when delivered via MVA. Moreover, in vitro co-infection of macrophages with MVA-based vaccine vectors and the ISG15AA mutant led to a marked increase in proinflammatory cytokine production, highlighting a dominant role for the extracellular, ISGylation-independent functions of ISG15 in shaping vaccine-induced immunity. Notably, co-infection of ISG15 with MVA-ZIKV and MVA-SARS-CoV-2 vaccine candidates enhanced the magnitude of antigen-specific immune responses in both vaccine models. Conclusions: ISG15, particularly in its ISGylation-deficient form, acts as a promising immunomodulatory adjuvant for viral vaccines, enhancing both innate and adaptive immune responses. Consistent with previous findings in the context of Human Immunodeficiency virus type 1 (HIV-1) vaccines, this study further supports the potential of ISG15 as an effective adjuvant for vaccines targeting viral infections such as ZIKV and SARS-CoV-2. Full article

The COVID-19 pandemic has revealed the profound and lasting impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the nervous system. Beyond acute infection, SARS-CoV-2 acts as a potent immunomodulatory agent, disrupting immune homeostasis and contributing to persistent inflammation, autoimmunity, and neurodegeneration. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by a spectrum of neurological symptoms, including cognitive dysfunction, fatigue, neuropathy, and mood disturbances. These are linked to immune dysregulation involving cytokine imbalance, blood–brain barrier (BBB) disruption, glial activation, and T-cell exhaustion. Key biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) correlate with disease severity and chronicity. This narrative review examines the immunopathological mechanisms underpinning the neurological sequelae of long COVID, focusing on neuroinflammation, endothelial dysfunction, and molecular mimicry. We also assess the role of viral variants in shaping neuroimmune outcomes and explore emerging diagnostic and therapeutic strategies, including biomarker-guided and immune-targeted interventions. By delineating how SARS-CoV-2 reshapes neuroimmune interactions, this review aims to support the development of precision-based diagnostics and targeted therapies for long COVID-related neurological dysfunction. Emerging approaches include immune-modulatory agents (e.g., anti-IL-6), neuroprotective drugs, and strategies for repurposing antiviral or anti-inflammatory compounds in neuro-COVID. Given the high prevalence of comorbidities, personalized therapies guided by biomarkers and patient-specific immune profiles may be essential. Advancements in vaccine technologies and targeted biologics may also hold promise for prevention and disease modification. Finally, continued interdisciplinary research is needed to clarify the complex virus–immune–brain axis in long COVID and inform effective clinical management. Full article

Summary: COVID-19, caused by SARS-CoV-2, has been associated with a range of cardiovascular complications, including myocarditis. This review aims to systematically present the clinical manifestations, underlying pathophysiological mechanisms, diagnostic approaches, and management strategies for both COVID-19-associated myocarditis and myocarditis related to SARS-CoV-2 vaccination. We conducted a literature search using the PubMed database, covering studies published up to early 2024. Search terms included combinations of “COVID-19”, “Coronavirus”, “SARS-CoV-2”, and/or “vaccination” with “cardiac injury”, “cardiac inflammation”, “myocarditis”. The reported prevalence of COVID-19-associated myocarditis varies between 2.3% and 5.0%, though myocardial injury is more frequently observed than confirmed myocarditis. Pathophysiological mechanisms include direct viral damage, immune-mediated injury, and molecular mimicry. Clinically, patients may present with chest pain, dyspnea, and fever. Diagnostic workup includes electrocardiography (ECG), troponin measurement, echocardiography, cardiac magnetic resonance imaging (cMRI), and in selected cases, endomyocardial biopsy (EMB). The management and disposition of COVID-19-associated myocarditis varies according to severity, especially to allow targeted treatment of complications. Glucocorticoids are a mainstay of treatment in severe cases. Myocarditis following SARS-CoV-2 vaccination is rare, more frequently reported in males under 30 years, and is generally associated with a favorable prognosis. Despite this, the benefits of vaccination continue to outweigh the risks. COVID-19 is associated with an increased risk of heart failure and other cardiovascular complications, underlining the importance of long-term follow-up and preventive strategies. Further research is needed to better understand the pathogenesis and optimal management of myocarditis in the context of COVID-19, with the goal of developing evidence-based therapeutic algorithms. Full article