Introduction: Finding potential antiviral inhibitors has advanced significantly through computer-aided drug discovery. Methods: The Random Forest regression (RFR), PLS regression, NNKernel regression, and pcRegression models were compared and assessed using R². In the following step, molecular docking was conducted to assess binding affinities and protein-ligand interactions. The ligand with the highest ICM score was subjected to molecular dynamics simulations to analyze binding and mechanism. In the final step, network pharmacology was adopted to study the mechanism of action. Results: The R² value for RFR is 0.93, indicating that the model performed exceptionally well in terms of prediction, with highly correlated experimental and predicted values. The ML model showed that only 152 out of the 186 compounds have pIC50 values greater than 6. Ligands with pIC50 values greater than 6 were selected for molecular docking with the NS2B/NS3 protease. Molecular docking studies revealed that 28 of the 152 compounds have ICM scores below 0, and five compounds were selected at the top of the list based on their binding interactions and ICM scores. The compound that was ranked highest, PubChem IDs 44626355, 166633044, 166633428, 20873605, and 166626117, had ICM scores of -21.657148, -19.151558, -16.963572, -16.836168, and -15.635322 kcal/mol. Discussion: PubChem CID: 44626355 compound’s binding stability is attributed to strong hydrogen bonding, van der Waals, and hydrophobic interactions. Molecular dynamics simulations, PCA, and FEL were conducted. Through network pharmacology, the therapeutic mechanism emerges that acts across several interconnected pathways involved in dengue pathology. Conclusion: Our study offers a promising framework for identifying potent inhibitors of the dengue virus.
INTRODUCTION:Long COVID syndrome (LCS) is characterized by persistent neurological, respiratory, and systemic symptoms following SARS-CoV-2 infection, with limited effective treatments available. Viusid is an oral antioxidant and immunomodulatory formulation that may improve chronic inflammatory symptoms. This study evaluated the efficacy of Viusid in patients with LCS. METHODS:This randomized double-blind placebo-controlled clinical trial evaluated the efficacy and safety of Viusid in adults with long COVID syndrome. The primary endpoint was the change in brain fog severity at Day 210. Secondary endpoints included changes in neurological, respiratory, musculoskeletal, digestive, and general symptoms measured using a 23-symptom clinical questionnaire. RESULTS:All participants completed the study. Viusid significantly improved the primary endpoint, brain fog, compared with placebo (MD -1.23; 95% CI -2.41 to -0.005; p < 0.001). Significant improvements favoring Viusid were also observed in anxious-depressive mood (p < 0.001), sleep dis-orders (p = 0.003), fatigue (p = 0.023), dyspnea (p = 0.018), chest pain (p = 0.002), cough (p = 0.004), abdominal pain (p = 0.009), and myalgia (p = 0.025). These effects remained consistent after adjusted analyses. DISCUSSION:The intervention showed potential improvement in long COVID symptoms; however, the small sample size and observational design limit conclusions, warranting further randomized con-trolled studies. CONCLUSIONS:Viusid significantly improved multiple long COVID symptoms, particularly neurological and respiratory manifestations. These findings support its potential as a therapeutic option for long COVID and justify further confirmatory studies.
BACKGROUND:Rickettsial diseases have re-emerged as significant causes of acute febrile illness in India and can occasionally evolve into rickettsial endovasculitis, characterized by widespread endothelial infection and vascular inflammation, leading to increased vascular permeability, tissue ischemia, and multiorgan dysfunction. Early diagnosis remains challenging because the initial clinical presentation is often nonspecific, and rapid diagnostic facilities are not uniformly available in many healthcare settings. CASE PRESENTATION:We describe a 17-year-old previously healthy female who presented after 10 days of fever and rapidly deteriorated, developing Acute Respiratory Distress Syndrome (ARDS), Acute Kidney Injury (AKI), hepatic impairment, and myocardial involvement. Serological testing demonstrated a positive Weil-Felix OX-K titer (OX-K ≥ 1:160), supporting a rickettsial etiology. Despite prompt doxycycline therapy, adjunctive corticosteroids for ARDS, renal replacement therapy, and lung-protective mechanical ventilation, the patient developed refractory hypoxemia (PaO₂ < 60 mmHg despite optimized ventilatory support) and circulatory collapse, resulting in death on the fifth hospital day. This case demonstrates a rapidly progressive, severe vasculitic form of rickettsial disease culminating in severe multiorgan dysfunction (severe ARDS, acute renal impairment, and myocarditis). The lack of classical clinical markers, such as eschar, along with significant overlap with other endemic tropical infections, likely delayed definitive diagnosis. CONCLUSION:In rickettsial-endemic settings, clinicians should retain a high index of suspicion for these infections in patients presenting with undifferentiated febrile illness. Prompt initiation of doxycycline, improved access to rapid diagnostic tools, and early escalation to intensive care are essential strategies to reduce mortality and prevent fatal complications.
Introduction: Toxoplasmosis is a food-borne disease that infects almost all warm-blooded mammals and birds. Birds are considered intermediate hosts for the parasite. The consumption of infected birds by humans and other animals plays a highlight role in the transmission of this parasite. Accordingly, the present review was conducted to find the global seroprevalence of T. gondii in birds. Methods: A comprehensive search of five academic databases (ScienceDirect, PubMed, Web of Science, ProQuest, and Scopus) and Google Scholar was conducted for literature published from 1952 to December 13, 2020. Results: Finally, a total of 211 studies, including 69006 birds (from 61 countries), were incorporated in the present study. The seroprevalence was calculated at 27.96% (95% CI=25.27-30.73) based on the random effect. The pooled seroprevalence rates of T. gondii were in Africa (39.73%), America (34.50%), Asia (23.65%), and Europe (17.46%). Based on these results, the Modified Agglutination Test (MAT) was the most common diagnostic method (122 studies). The weighted prevalence was higher in free-range chickens (37.60%) and domestic chickens (36.93%) than in other bird types. Discussion: Based on the findings of the study, a high seropositivity of T. gondii in birds indicates that they could be a potential food safety risk for humans. Conclusion: The current review has contributed to enhancing the understanding of the relatively high level of T. gondii seroprevalence in birds. The results from this study are useful for policymakers to control T. gondii infection in meat consumption, due to the significant role of poultry in the human diet.
Photodynamic therapy (PDT) has been investigated as a minimally invasive approach that could enhance reproductive health by preserving the reproductive tract microbiome. The disturbances in the reproductive tract microbiome, including the loss of Lactobacillus-dominated communities and the overgrowth of opportunistic or pathogenic bacteria, are associated with infertility. PDT can be used to eliminate specific pathogens or precancerous lesions, and may modulate the microbiome in the female genital tract. Unlike conventional antimicrobial treatments, which may also affect beneficial microorganisms, PDT can selectively inactivate pathogenic microbes through the generation of reactive oxygen species (ROS). Maintaining a balanced cervicovaginal microbiome is of great importance in achieving reproductive success. By reducing pathogenic microbial load and limiting damage to commensal bacteria, PDT may contribute to improving microbial balance in the cervicovaginal environment. In recent years, there has been increasing attention to therapeutic strategies in reproductive medicine that preserve the microbiome, emphasizing the importance of methods that control infection while maintaining a balanced microbial ecosystem. This narrative mini‑review summarizes current findings on the use of PDT for microbial modulation in the female reproductive tract and discusses its relevance in the treatment of infertility associated with reproductive tract microbial dysbiosis.
