Search Results (272)

Background: Studies investigating the long-term cellular immune response to SARS-CoV-2 mRNA vaccines in patients with inflammatory bowel disease (IBD) remain limited, particularly among those receiving immunosuppressive therapy. Methods: We prospectively evaluated humoral and cellular immune responses at short-term (4–6 weeks) and long-term (6–12 months) time points following SARS-CoV-2 mRNA vaccination in patients with IBD receiving anti-TNF agents, thiopurines, or combination therapy. We defined the short-term response as the measurement taken 4–6 weeks after the second vaccine dose and the long-term response as the measurement taken between 6 and 12 months after the first determination. A cohort of healthy controls was included for short-term comparative analysis. Results: At long-term follow-up, quantitative humoral responses were reduced in patients receiving anti-TNF monotherapy. In contrast, a reduced quantitative cellular response was found in the thiopurine (median 0.7 UI/mL, p < 0.05) and anti-TNF combo groups (median 0.4 UI/mL, p < 0.01) compared to anti-TNF monotherapy (median 2.2 UI/mL). Conclusions: There was a robust long-term humoral and cellular response to vaccination, but a diminished quantitative cellular response in patients treated with thiopurines or combo therapy compared to anti-TNF monotherapy. Full article

The global impact of the COVID-19 crisis has underscored the need for novel therapeutic candidates capable of efficiently targeting essential viral proteins. Existing therapeutic strategies continue to encounter limitations such as reduced efficacy against emerging variants, safety concerns, and suboptimal pharmacodynamics, which emphasize the potential of natural-origin compounds as supportive agents with immunomodulatory, anti-inflammatory, and antioxidant benefits. The present study significantly advances prior molecular docking research through comprehensive virtual screening of structurally related analogs derived from antiviral phytochemicals. These compounds were evaluated specifically against the SARS-CoV-2 main protease (3CLpro) and papain-like protease (PLpro). Utilizing chemical similarity algorithms via the ChEMBL database, over 600 candidate molecules were retrieved and subjected to automated docking, interaction pattern analysis, and comprehensive ADMET profiling. Several analogs showed enhanced binding scores relative to their parent scaffolds, with CHEMBL1720210 (a shogaol-derived analog) demonstrating strong interaction with PLpro (−9.34 kcal/mol), and CHEMBL1495225 (a 6-gingerol derivative) showing high affinity for 3CLpro (−8.04 kcal/mol). Molecular interaction analysis revealed that CHEMBL1720210 forms hydrogen bonds with key PLpro residues including GLY163, LEU162, GLN269, TYR265, and TYR273, complemented by hydrophobic interactions with TYR268 and PRO248. CHEMBL1495225 establishes multiple hydrogen bonds with the 3CLpro residues ASP197, ARG131, TYR239, LEU272, and GLY195, along with hydrophobic contacts with LEU287. Gene expression predictions via DIGEP-Pred indicated that the top-ranked compounds could influence biological pathways linked to inflammation and oxidative stress, processes implicated in COVID-19’s pathology. Notably, CHEMBL4069090 emerged as a lead compound with favorable drug-likeness and predicted binding to PLpro. Overall, the applied in silico framework facilitated the rational prioritization of bioactive analogs with promising pharmacological profiles, supporting their advancement toward experimental validation and therapeutic exploration against 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

The diversity of structural types of carrageenans (CRGs)—sulfated polysaccharides of red algae—determines their different biological activities. The different types of CRGs (kappa, lambda, kappa/beta-CRGs) were isolated from the red algae of the Pacific coast. Molecular docking was performed to determine potential interactions of CRGs with the receptor-binding domain (RBD) of SARS-CoV-2 and its cellular receptor—angiotensin—converting enzyme type 2 (ACE2). CRGs interacted with ACE2 and RBD via hydrogen bonding and ionic interactions. The strongest binding affinity of CRGs and ACE2 was observed for kappa-CRG. Molecular docking was confirmed by results studying the effects of CRGs against SARS-CoV-2 in vitro. The ability of CRGs, as well as the complex CRG with sea urchin echinochrome (Ech), to inhibit SARS-CoV-2 replication in Vero E6 cells was studied using cytopathic effect (CPE) inhibition and RT-PCR assays. The simultaneous treatment of cells with CRGs and the virus revealed that kappa-CRG exhibited the most significant antiviral effect among all the polysaccharides, with a selective index (SI) of 33. The kappa-CRG/Ech complex exhibited the highest virucidal effect on SARS-CoV-2 particles with an SI above 70 (more than two times higher than that of CRG and Ech) and reduced viral RNA levels by 45% (IC = 45%). Our results illustrate that CRGs and kappa-CRG/Ech complex can act as protective agents against SARS-CoV-2. Full article

Backgrounds and Objectives: Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but potentially severe complication of SARS-CoV-2 infection, with increasingly reported renal manifestations. Materials and Methods: The aim of this retrospective study was to compare clinical and laboratory characteristics across age categories, with special emphasis on renal function. We analysed data from 64 patients with MIS-C treated between July 2020 and December 2023. Results: In children under 3 years of age, there was a higher prevalence of leucocytosis, elevated platelet counts, and anaemia, along with a lower frequency of complications. The 3–6-year age group was characterized by the presence of rash, hypoalbuminemia, and elevated transaminases. The 7–12-year age group showed the highest rate of organ dysfunction. In adolescents (13–18 years), neurological symptoms, the highest BMI values, the greatest prevalence of comorbidities, leukopenia, lymphopenia, and elevated GGT levels were observed. The incidence of acute kidney injury (AKI) was 6.3% (n = 4/64). Following treatment, the majority of patients achieved full recovery (n = 61/64; 95.2%). Conclusions: There are pronounced age-related differences in the clinical presentation of MIS-C, with distinct immune and clinical patterns suggesting developmental influences on disease expression and outcomes. Older children showed a higher prevalence of comorbidities and organ dysfunction compared to younger patients. Notably, this study found a markedly lower incidence of acute kidney injury (6.3%) compared to previously reported rates (20–30%), indicating potential regional or age-related protective factors. These findings highlight the importance of age-specific evaluation in MIS-C and underscore the need for further multicentre research to refine therapeutic protocols. Full article

Respiratory viruses can cause life-threatening conditions such as sepsis and acute respiratory distress syndrome. However, vaccines and effective antivirals are available for only a limited number of infections. The majority of approved antivirals are direct-acting agents, which target viral proteins essential for infection. Unfortunately, mutations have already emerged that confer resistance to these antivirals. In addition, there is an urgent need for broad-spectrum antivirals to address the unpredictable emergence of new viruses with pandemic potential. One promising strategy involves modulating the innate immune response and cellular signaling. Imiquimod, a Toll-like receptor 7 (TLR7) agonist, has shown efficacy in murine models of influenza and respiratory syncytial virus (RSV). Additionally, it demonstrates antiviral activity against herpes simplex virus type 1 (HSV-1) and RSV independent of the TLR7/nuclear factor kappa B (NF-κB) pathway, with protein kinase A (PKA) as a crucial downstream effector. In this study, we demonstrate that imiquimod exhibits concentration-dependent antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and canine coronavirus (CCoV) in epithelial cells, underscoring its broad-spectrum action against coronaviruses. Moreover, its anti-coronavirus effect appears to be independent of the TLR/NF-κB and PKA/exchange protein directly activated by cyclic adenosine monophosphate (EPAC) pathways and may instead be linked to the activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. The ability of imiquimod to inhibit coronavirus replication via the MEK/ERK pathway, coupled with its immunomodulatory properties, highlights its potential as a broad-spectrum antiviral. Full article

Background/Objectives: Highly pathogenic coronaviruses (CoVs), including SARS-CoV, MERS-CoV, and SARS-CoV-2, continue to pose a significant threat to global public health. Therefore, this situation highlights the urgent need for effective broad-spectrum antiviral agents. Curcumin, a naturally occurring polyphenol known for its antiviral and anti-inflammatory properties, faces limitations such as poor bioavailability and rapid metabolic degradation, restricting its practical therapeutic application. Methods: To address these limitations, this study introduces a novel design strategy aimed at 42 new curcumin derivatives with improved pharmacokinetic profiles, specifically targeting the conserved coronavirus enzyme papain-like protease (PLpro). A comprehensive in silico evaluation was performed, including ADMET (Absorption, Distribution, Metabolism, Elimination, and Toxicity) analysis, molecular docking, molecular dynamics (MD) simulations, and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) calculations. Results: Extensive pharmacokinetic and toxicological assessments (ADMET analyses) identified 19 derivatives exhibiting optimal drug-like characteristics according to Lipinski’s Rule of Five (Ro5). Molecular docking analyses demonstrated that these novel derivatives possess significantly enhanced binding affinities to PLpro enzymes from SARS-CoV, MERS-CoV, and SARS-CoV-2 compared to standard antiviral agents and natural curcumin. Further validation through MD simulations and MM/PBSA calculations confirmed the structural stability and robust interactions of the most promising derivatives within the SARS-CoV PLpro active site. Conclusions: The results of this study provide essential structural and functional insights, reinforcing the potential of these newly developed curcumin derivatives as potent, broad-spectrum antiviral agents effective against current and future coronavirus threats. Full article

The human coronavirus 229E (HCoV-229E) is a member of the human coronavirus family that includes SARS-CoV-2, the causative agent of COVID-19. Developing antiviral strategies and compounds is crucial to treat and prevent HCoV-229E infections and the associated diseases. Ribozymes derived from ribonuclease P (RNase P) catalytic RNA represent a novel class of promising gene-targeting agents by cleaving their target mRNA and knocking down the expression of the target mRNA. However, it has not been reported whether RNase P ribozymes block the infection and replication of HCoV-229E. We report here the engineering of an anti-HCoV-229E RNase P ribozyme to target an overlapping region of viral genomic RNA and the mRNA encoding the nucleocapsid (N) protein, which is vital for viral replication and growth. The engineered ribozyme actively hydrolyzed the viral RNA target in vitro. HCoV-229E-infected cells expressing the engineered, catalytically active ribozyme exhibited a reduction of about 85% in viral RNA levels and N protein expression, and a reduction of about 750-fold in infectious particle production, compared to cells expressing no ribozymes or a control, catalytically inactive ribozyme. Our study provides the first direct evidence of the therapeutic potential of RNase P ribozymes against human coronaviruses such as HCoV-229E. Full article

Immunocompromised (IC) patients continue to be at risk of severe COVID-19 despite vaccination and anti-SARS-CoV-2 therapies. The comparative effectiveness of antiviral agents (AVAs) and monoclonal antibodies (MoAbs) as early treatment of SARS-CoV-2 in IC patients is described in this work. This retrospective multicenter cohort study included IC outpatients diagnosed with SARS-CoV-2 between March 2021 and March 2022 at the National Institute for Infectious Diseases “Lazzaro Spallanzani” and Santa Maria Goretti University Hospital, Italy. Patients received either AVAs or MoAbs based on national guidelines. The primary outcome was time to negative nasopharyngeal swab (NPS). The secondary outcomes were COVID-19-related hospitalization or death by day 30. Among 1472 IC patients (with a median age of 58 years, 45% male), 688 (46%) were treated with MoAbs, and 783 (54%) were treated with AVAs. The patients treated with MoAbs had a higher duration to negative NPS (17 vs. 11 days, p < 0.05) and a higher risk of sustained SARS-CoV-2 positivity on day 7 (OR: 3.0, 95% CI: 1.72–5.23, p < 0.01) and day 30 (OR: 6.0, 95% CI: 3.7–10.5, p < 0.01) than those treated with AVAs. There were no differences in hospitalization or mortality. AVAs were associated with a more rapid viral clearance than MoAbs, suggesting a potential advantage for reducing infectious duration in IC patients. Additional studies are necessary to further optimize the early treatment of COVID-19 in this high-risk population. Full article

Background and Clinical Significance: Lung cancer, a leading cause of global cancer diagnoses, maintains the highest mortality risk despite advances in treatment. Immunotherapy agents, such as anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1), have revolutionized care for non-small cell lung cancer (NSCLC). However, the success is tempered by the emergence of immune-mediated adverse reactions, including the rare onset of type I diabetes. The incidence of diabetes mellitus increased during the SARS-CoV-2 pandemic. While there are several cases of new-onset diabetes after COVID-19 and COVID-19 vaccination, no case of new-onset type 1 diabetes after COVID-19 was described in an immune checkpoint inhibitor (ICI)-treated patient. Case Presentation: A 57-year-old male with stage IV NSCLC (brain and liver metastases) who had been treated with nivolumab for 4 years appeared positive for SARS-CoV-2 infection at a routine check. After two weeks, he was admitted to our clinic with severe fatigue, hyperglycemia, hyponatremia, and hyperkalemia. HbA1c level was normal and serum peptide C was undetectable. Nivolumab treatment was ceased, and the patient became fully dependent on basal–bolus insulin. After 3 months, the patient showed a complete imagistic remission. Conclusions: The case presented significant challenges due to the unclear etiology of newly onset diabetes and the uncommon age at which type 1 diabetes is developed. The outcome suggests that anti-PD-1 and SARS-CoV-2 infection can act synergistically. Full article

Background: Breast milk is a rich source of antimicrobial and anti-inflammatory compounds, owing to its diverse array of bioactive molecules. This study explores the presence and activity of natural antimicrobial agents in breast milk, particularly in the context of the SARS-CoV-2 pandemic. Materials and Methods: Breast milk samples were collected from 50 breastfeeding mothers, including those who had either been vaccinated against SARS-CoV-2 or had recovered from the infection. These samples were compared with a control group consisting of 10 unvaccinated mothers with no history of COVID-19. Key antimicrobial and immune-regulatory proteins—lactoferrin, lactadherin, furin, tenascin C, granzyme B, and chitinase 3-like 1—were quantified using the Luminex multiplex analyzer. Results and Discussion: All targeted biomarkers were detected in breast milk, providing insights into the immune profile transferred to infants following COVID-19 infection or vaccination. These bioactive molecules highlight breastfeeding’s role in providing passive immunity and antimicrobial protection. The protein levels were found to be influenced by factors such as maternal inflammation, infant age, delivery mode, and parity, emphasizing the dynamic interaction between maternal immunity, lactation biology, and infant development. Conclusion: Breastfeeding serves as a powerful anti-SARS-CoV-2 defense mechanism, supported by the activity of lactoferrin, lactadherin, and furin, reinforcing its critical role in child health. Full article

The COVID-19 pandemic highlighted the global necessity to develop fast, affordable, and user-friendly diagnostic alternatives. Alongside recognized tests such as ELISA, nanotechnologies have since been explored for direct and indirect diagnosis of SARS-CoV-2, the etiological agent of COVID-19. Accordingly, in this work, we report a method to detect anti-SARS-CoV-2 antibodies based on graphene-based field-effect transistors (GFETs), using a nanostructured platform of graphene with added gold nanorods (GNRs) and a specific viral protein. To detect anti-N-protein IgG antibodies for COVID-19 in human sera, gold nanorods were functionalized with the nucleocapsid (N) protein of SARS-CoV-2, and subsequently deposited onto graphene devices. Our test results demonstrate that the sensor is highly sensitive and can detect antibody concentrations as low as 100 pg/mL. Using the sensor to test human sera that were previously diagnosed with ELISA showed a 90% accuracy rate compared to the ELISA results, with the test completed in under 15 min. Integrating graphene and nanorods eliminates the need for a blocker, simplifying sensor fabrication. This hybrid sensor holds robust potential to serve as a simple and efficient point-of-care platform. Full article

Individuals infected with COVID-19 often experience the distressing discomfort of pharyngitis. Thus, it is crucial to develop novel drugs to improve therapeutic options. In this study, we investigated the interaction between bioactive compounds isolated from Acanthopanax trifoliatus (L.) Merr and proteins associated with COVID-19 and pharyngitis through in silico analysis. Several molecules demonstrated high affinities to multiple targets, indicating significant potential for alleviating pharyngitis and other COVID-19-related symptoms. Among them, rutin and isochlorogenic acid C, two major components in Acanthopanax trifoliatus (L.) Merr ethanol extracts, were further experimentally demonstrated to exhibit strong inhibitory effects against SARS-CoV-2 and to possess significant anti-inflammatory activities. Inhibition of over 50% in several key genes was observed, demonstrating the efficacy of in silico methods in identifying high-affinity target binders. Our findings provide a theoretical foundation for the development of Acanthopanax trifoliatus (L.) Merr as a novel multi-target therapeutic agent for both COVID-19 and pharyngitis. Full article

The purpose of this review is to propose that lipoxin A4 (LXA4), derived from arachidonic acid (AA), a potent anti-inflammatory, cytoprotective, and wound healing agent, may be useful to prevent and manage diabetic retinopathy (DR). LXA4 suppresses inappropriate angiogenesis and the production of pro-inflammatory prostaglandin E2 (PGE2), leukotrienes (LTs), 12-HETE (12-hydroxyeicosatetraenoic acid), derived from AA by the action of 12-lioxygenase (12-LOX)) interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), as well as the expression of NF-κB, inducible NO (nitric oxide) synthase (iNOS), cyclooxygenase-2 (COX-2), intracellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF)—factors that play a role in DR. Thus, the intravitreal injection of LXA4 may form a new approach to the treatment of DR and other similar conditions such as AMD (age-associated macular degeneration) and SARS-CoV-2-associated hyperinflammatory immune response in the retina. The data for this review are derived from our previous work conducted in individuals with DR and from various publications on LXA4, inflammation, and DR. Full article

Background: p97 (also known as valosin-containing protein, VCP) is a member of the AAA+ ATPase family and is intimately associated with protein quality control and homeostasis regulation. Therefore, pharmaceutical inhibition of p97 has been actively pursued as an anticancer strategy. Recently, p97 has emerged as an important pro-viral host factor and p97 inhibitors are being evaluated as potential antiviral agents. Methods: We designed and synthesized novel p97 inhibitors based on the rearrangement of the central fused ring of our previously reported p97 inhibitors. These compounds were tested for inhibition of p97, cytotoxicity, and antiviral activity against SARS-CoV-2. Molecular docking was also performed on selected inhibitors to shed light on their binding modes. Results: Among these new p97 inhibitors, two compounds possess enhanced anti-p97 activity over their parent compounds. More significantly, these two inhibitors exhibit strong antiviral activity against SARS-CoV-2 at doses with no significant cytotoxicity. Molecular docking reveals no major change of the binding mode relative to that of their parent compounds, further supporting our design strategy. Conclusions: These compounds are structurally novel p97 inhibitors that display low toxicity and possess promising antiviral activity against SARS-CoV-2 and potentially other viruses. Further structural exploration is therefore justified and improved analogs will serve as useful tools for studying p97 as a promising host antiviral target. Full article