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Statins are among the most frequently prescribed medications. In addition to their well-established effectiveness in lowering total cholesterol, LDL, and triglycerides, statins have been described to have immunomodulatory and anti-inflammatory properties and have been associated with improved endothelial functions. Given the common use of statins, we sought to evaluate the effect of statins on some viral infections encountered by residents in tropical areas or by international travelers. A literature search was performed in PubMED/MEDLINE focusing on keywords that included statins and the viruses of interest, including SARS-CoV-2, influenza, yellow fever, dengue, Zika, tick-borne encephalitis, hemorrhagic fever viruses, hepatitis A, norovirus, hepatitis B, hepatitis C, measles, and herpesviruses; findings were synthesized for each virus into a summary. The effects of statins on viral infections vary depending on the specific virus. While some studies indicate potential benefits in chronic HBV and HCV infections, evidence regarding SARS-CoV-2 and influenza remains inconclusive due to mixed findings from observational studies and randomized controlled trials. The role of statins in other viral infections is largely unexplored, with preclinical data available for only a few viruses. Given the conflicting evidence, further prospective studies and randomized controlled trials are warranted to elucidate statins’ role in viral infections, particularly in modulating inflammation, endothelial dysfunction, and immune responses. Future research should aim to define the optimal patient populations, target viruses, statin types, and treatment durations that may confer benefits in specific viral infections. Full article

Acute pharyngotonsillitis is a common reason to visit primary care providers. Group A Streptococcal (GAS) pharyngitis is the most common bacterial infection which needs antibiotic treatment. GAS accounts for only 10–15% of adult acute pharyngitis cases. The overuse of antibiotics for viral pharyngotonsillitis is common and may lead to inappropriate antimicrobial stewardship and the emergence of bacterial resistance. However, the etiology of acute pharyngotonsillitis for hospitalized adult patients is rarely studied. So, we reported the 10-year surveillance data of hospitalized adult patients with acute pharyngotonsillitis in a regional hospital in Taiwan. Every consecutive adult patient admitted with acute pharyngotonsillitis in 2011–2021 was recruited for a complete etiology study. The etiology of acute pharyngotonsillitis was identified in 117 patients. Overall, 42 herpes simplex virus cases, 26 adenovirus cases, 16 acute human immunodeficiency virus cases, 12 influenza cases, three parainfluenza cases, six Epstein–Barr virus cases, one cytomegalovirus case, four enterovirus cases, one varicella-zoster virus case, four Mycoplasma pneumoniae cases, one Chlamydophila pneumoniae case, and only one GAS case were identified. The average of the points for the Modified Centor Criteria was 1.38 (55% of patients with 0–1 points and 45% with 2–3 points). However, 88.9%of patients received antibiotics at the emergency department, and 76.9%also received antibiotics while hospitalized. Only a few patients required antibiotic treatment, while the majority of patients with viral illness needed only symptomatic treatment. However, distinguishing viral etiology from GAS pharyngitis is challenging even in the presence of tonsil exudates, high C-reactive protein, and leukocytosis. A diagnostic algorithm and the application of the Modified Centor Criteria should be considered for hospitalized adults with acute pharyngotonsillitis to improve antimicrobial stewardship. Full article

Background/Objectives: Targeted delivery of antigens to dendritic cells (DCs) is an effective strategy for enhancing vaccine efficacy. Methods: In this study, dual-targeting fusion proteins (GRFT-VHH54 and GRFT-VHH74) were constructed by fusing Griffithsin (GRFT), an algae-derived lectin with enveloped virus-binding properties, to DC-specific binding nanobodies (VHH54 and VHH74). Vaccines were formulated by combining the inactivated H9N2 avian influenza virus with these fusion proteins, and the potential of the fusion proteins to enhance vaccine-induced immunity in chickens was systematically evaluated. For parallel comparison, control groups included H9N2 avian influenza vaccines containing the inactivated virus alone, the inactivated virus with the immune enhancer CVCVA5, and a commercial H9N2 avian influenza inactivated vaccine. Results: At 4 weeks post-immunization, chickens vaccinated with the inactivated H9N2 virus combined with the GRFT-VHH74 fusion protein (1/2 H9+GRFT-VHH74) exhibited significantly enhanced humoral, mucosal, and cellular immune responses compared to those vaccinated with the inactivated H9N2 virus alone or the commercial H9N2 vaccine (p < 0.05). Additionally, chickens in the 1/2 H9+GRFT-VHH74 group exhibited enhanced resistance to the heterologous H9N2 subtype avian influenza virus, achieving a 90% protection rate, which was higher than that of the other groups. Conclusions: These results indicate that the GRFT-VHH74 fusion protein has significant potential for advancing the development of inactivated vaccines against the H9N2 subtype avian influenza. Furthermore, it provides valuable insights for enhancing the immunogenicity and efficacy of inactivated vaccines targeting other avian influenza subtypes. Full article

Background: COVID-19 has largely become an endemic disease in many regions, with sporadic outbreaks, with some areas where the disease shows a seasonal pattern like the influenza virus. The focus has shifted towards managing mild and moderate forms of disease through outpatient care, aiming to prevent healthcare system overload. Consequently, identifying markers that could be used in stratifying the risk and the prognostic assessment has become crucial. Cardiovascular implications of COVID-19 are a critical area of research due to their significant impact on disease severity, mortality, and morbidity. Methods: We conducted a retrospective, observational study and included 472 patients, diagnosed with COVID-19, all of whom were admitted to Prof. Dr. Matei Bals National Institute of Infectious Disease, Bucharest, Romania. Levels of cardiac biomarkers like creatine kinase (CK), creatine kinase-myocardial band (CKMB), myoglobin, troponins, and NT-pro-BNP were measured and analyzed in relation to clinical presentation and outcomes. Results: We combined CKMB, myoglobin, and troponin I to predict hospital length of stay (LOS). Our model significantly predicted LOS (F = 12.537, p = 0.0001), with higher levels associated with prolonged stays (β = 0.166, p = 0.000). Logistic regression demonstrated that the combination of elevated CKMB and myoglobin levels significantly increased the odds of a longer LOS (OR = 1.679, p = 0.000). Furthermore, we found significant correlations with acute respiratory failure (p = 0.001), severe forms of disease (p = 0.000), and the development of complications during hospitalization (p = 0.027). Conclusions: These findings emphasize the value of combining cardiac biomarkers to stratify risk and predict hospital outcomes in COVID-19 patients. Routine cardiac monitoring and targeted management strategies could decrease the risk of complications, reducing the LOS. Our findings highlight the potential of cardiac biomarkers as prognostic tools to stratify risk, guide clinical interventions, and improve outcomes in COVID-19 patients. Full article

In recent years, the incidence of Severe Acute Respiratory Infection (SARI) has increased due to the emergence of SARS-CoV-2. However, the impact of the COVID-19 pandemic extends beyond mortality rates. Recent analyses suggest that the introduction and spread of SARS-CoV-2 have significantly affected the epidemiology of other key respiratory viruses, such as influenza virus (FLUV), respiratory syncytial virus (RSV), and rhinovirus (RV). These changes raise new questions about the dynamics and incidence of post-COVID-19 respiratory infections, as well as potential alterations in symptom profiles and clinical outcomes. In this study, we analyzed data from the Epidemiological Surveillance Information System of Respiratory Viral Agents (SIVEP-Gripe), established by the Brazilian Ministry of Health, to examine the profile of SARI before and during the COVID-19 pandemic in Brazil. Our data reveal a distinct epidemiological pattern, with a significant decrease in FLUV notifications during the pandemic, accompanied by peaks in RSV and RV cases in late 2020. Additionally, there was a shift in the age distribution of RSV and other viral infections, with individuals infected during the pandemic being older than those infected before the pandemic. Interestingly, the introduction and spread of SARS-CoV-2 in Bahia State resulted in a reduction in the frequency of symptoms associated with non-SARS-CoV-2 SARI, without altering clinical outcomes. Our findings suggest that the circulation of SARS-CoV-2 has contributed to a clinical and epidemiological shift, particularly for FLUV, RSV, and other viruses, marked by a reduction in symptoms such as fever, dyspnea, respiratory distress, and the need for ventilatory support. The underlying mechanisms driving these changes remain unclear. These insights are crucial for public health authorities and policymakers to refine surveillance strategies and enhance control measures for respiratory viruses, particularly those causing SARI. Full article

Background/Object: This study investigates the in vitro antiviral potential of D-limonene (DLM), monolaurin (ML), and cetylpyridinium chloride (CPC) in formulations targeting SARS-CoV-2 and influenza viruses. The aim was to develop oral and nasal formulations with optimized concentrations of these active ingredients to evaluate their efficacy, safety, and stability. Methods: Oral (formulation D) and nasal (formulation E) products were developed using specific concentrations of DLM (0.2–0.3% w/w), ML (0.1–0.2% w/w), and CPC (0.05–0.075% w/w). In vitro virucidal activity assays were conducted to assess the antiviral efficacy of the formulations against SARS-CoV-2 and influenza viruses. Stability testing was also performed under various storage conditions. Results: Formulation D (0.3% w/w DLM, 0.2% w/w ML, 0.05% w/w CPC, and 1.5% w/w Cremophor RH40) demonstrated a 3.875 ± 0.1021 log reduction and 99.99 ± 0.0032% efficacy against SARS-CoV-2 within 120 s. Formulation E (0.2% w/w DLM, 0.05% w/w CPC, and 0.75% w/w Cremophor RH40) showed a 2.9063 ± 0.1197 log reduction and 99.87 ± 0.0369% efficacy against SARS-CoV-2. Both formulations achieved >99.99% efficacy and log reductions exceeding 4.000 against various influenza strains. Stability testing confirmed optimal performance at 4 °C with no microbial contamination. Conclusions: The findings suggest that both formulations exhibit broad-spectrum antiviral activity against SARS-CoV-2 and influenza viruses in vitro. These results support their potential for further clinical evaluations and therapeutic applications, particularly in oral and nasal spray formulations. Full article

The pandemic threat from newly emerging viral diseases constitutes a major unsolved issue for global health. Antiviral therapy can play an important role in treating and preventing the spread of unprecedented viral infections. A repository of compounds exhibiting broad-spectrum antiviral activity against a series of different viral families would be an invaluable asset to be prepared for future pandemic threats. Utilizing an open innovation crowd-sourcing paradigm, we were able to identify a compound class of diphenylureas that exhibits in vitro antiviral activity against multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adenovirus, dengue virus, herpes, and influenza viruses. Compound 4 among the series exhibits strong activity against dengue virus, a growing global health problem with high medical need and no approved antiviral drug. The compounds are active against SARS-CoV-2 in a primary human stem cell-based mucociliary airway epithelium model and also active in vivo, as shown in a murine SARS-CoV-2 infection model. These results demonstrate the potential of the chemical class as antivirals on the one hand and the power of open innovation, crowd-sourcing, and repurposing on the other hand. Full article

This study investigated the phytochemical profiles and bioactivities of two edible boletes from Southwestern China, Phlebopus portentosus and Butyriboletus roseoflavus. A total of 33 secondary metabolites, comprising 15 alkaloids, 4 pulvinic acid derivative pigments, and 14 ergosterols, were isolated and identified. To our best knowledge, boletesine A (1), boletesine B (2), and cis-xerocomic acid (16) were previously undescribed compounds. The new structures were established by extensive spectroscopic methods and chemical calculations. Compound 1 features a hitherto unknown hybrid skeleton formed between a 2-formylpyrrole-alkaloid and a dopacetic acid (DOPAC) via a Michael addition reaction. Bioactivity assays revealed the neuroprotective effects of compounds 18 and 19 against Aβ_25–35- or H₂O₂-induced toxicity. In a cytotoxic assay against a small panel of cancer cell lines, compound 9 exhibited significant activity against HeLa cells (IC₅₀ = 10.76 µM), while 33 demonstrated broad-spectrum cytotoxicity against Hela229, SGC7901, PC-3, and BEL7402 cells (IC_50s in the range of 20~30 µM). Of particular note is the anti-influenza virus activities against A/H3N2 and B/Victoria strains of compounds 22 and 26 (EC₅₀ values ranging from 3.6 to 9.6 µM). Along with these, compound 29 showed a moderate antiviral effect against coxsackievirus B3. These findings underscore the therapeutic potential of the two edible boletes in addressing neurodegenerative diseases, cancer, and viral infections, paving the way for their prospective applications in the development of functional foods and pharmaceuticals. Full article

Background: Infectious respiratory pathogens like SARS-CoV-2 and influenza frequently mutate, leading to the emergence of variants. This necessitates continuous updates to FDA-approved vaccines with booster shots targeting the circulating variants. Vaccine hesitancy and needle injections create inconvenience and contribute to reduced global vaccination rates. To address the burden of frequent painful injections, this manuscript explores the potential of non-invasive intranasal (IN) vaccine administration as an effective alternative to intramuscular (IM) shots. Further, as a proof-of-concept, an inactivated combination vaccine for COVID-19 and influenza was tested to eliminate the need for separate vaccinations. Methods: The methods involved encapsulating antigens and adjuvants in poly(lactic-co-glycolic acid) (PLGA) polymer matrices, achieving over 85% entrapment. The vaccine was evaluated in vitro for cytotoxicity and immunogenicity before being administered to 6–8-week-old Swiss Webster mice at weeks 0, 3, and 6. The mice were then assessed for antibody levels and cellular responses. Results: The intranasal microparticle (IN-MP) vaccine induced an innate immune response, autophagy, and were non-cytotoxic in vitro. In vivo, the vaccine led to high levels of virus-specific serum IgM, IgG, and IgA binding antibodies, as well as elevated IgG and IgA levels in the lung wash samples. The antibodies generated demonstrated neutralizing activity against the SARS-CoV-2 pseudovirus. Furthermore, the IN-MP vaccine prompted increased antigen-specific CD4⁺ and CD8⁺ T-cell responses in the vaccinated mice. Conclusions: The IN-MP combination vaccine produced immune responses comparable to or higher than the IM route, indicating its potential as an alternative to IM injections. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel human coronavirus, emerged in late 2019 and rapidly evolved into a pandemic around the world. The coronavirus disease (COVID-19) pandemic has dramatically changed the epidemiology and seasonality of other traditional respiratory viruses, e.g., influenza, respiratory syncytial virus, enterovirus, etc. These traditional respiratory viruses have transmission mode and clinical symptoms similar to SARS-CoV-2 but may differ in clinical outcomes and management. Co-infection between SARS-CoV-2 and one or more traditional respiratory viruses have been reported in the literature but have shown mixed evidence in clinical outcomes. With SARS-CoV-2 evolving into mild Omicron variants, it is believed that SARS-CoV-2 co-circulates with other respiratory viruses, which in turn affect the epidemiology and clinical course of respiratory viral infections. In response to these changes, multiplex molecular tests for SARS-CoV-2 and one or more traditional respiratory viruses are attracting more attention in the field and have been developed into a variety of testing modalities. In this review, we describe the seasonality (i.e., in the Northern Hemisphere), epidemiology, and clinical significance of traditional respiratory viruses and their co-infection with SARS-CoV-2 in the post-COVID era. Furthermore, we review commonly used multiplex molecular tests and their applications for the detection of respiratory viruses and their co-infections. Altogether, this review not only sheds light on the epidemiology and clinical significance of respiratory viral infections and co-infections in the post-COVID era, and but also provides insights into the laboratory-based diagnoses of respiratory viral infections using multiplex molecular testing. Full article

Pigs serve as critical reservoirs and amplifiers for numerous zoonotic viral diseases, presenting substantial public health challenges in India. This study highlights the epidemiology and emerging trends of key zoonotic viruses associated with pigs, emphasizing their role in endemic and emerging disease dynamics. Japanese encephalitis virus (JEV) persists as a major concern, with pigs acting as amplifying host, while hepatitis E virus (HEV) remains a prominent cause of viral hepatitis, transmitted via contaminated water and pork products. Emerging high-fatality viral zoonoses caused by Nipah virus (NiV) and recurrent threats from swine influenza virus (SIV) demonstrate that the zoonotic landscape is evolving. Furthermore, zoonotic viruses like rotavirus, pseudorabies (ADV or SuHV-1), porcine astrovirus (PAstV), and Torque teno sus virus (TTSuV) reflect the expanding diversity of pig-associated pathogens in India. Emerging evidence also implicates viruses such as Chandipura virus (CHPV) in localized outbreaks, indicating broader zoonotic potential. Novel risks such as swine acute diarrhea syndrome coronavirus (SADS-CoV) and SARS-CoV-2 emphasize the role of pigs as potential intermediaries for pandemic-prone viruses. This comprehensive study evaluates the prevalence, outbreak dynamics, and public health implications of zoonotic viral diseases of pigs in India, providing valuable direction for developing effective control measures. Full article

The nasal epithelium is the primary site for entry of respiratory viruses. In comparison to oral administration, nasal drug applications directed locally to the site of infection can serve as early interventional barriers against respiratory virus pathogenesis by limiting viral spread in the upper airway. Experiments on the diffusion of methylene blue and nanoparticles in both water and low pH conditions revealed that hydroxypropyl methylcellulose (HPMC) can act as an effective physical barrier. This study also evaluated the activity of HPMC as a barrier against common respiratory viruses, i.e., rhinovirus (RV) and influenza A virus (IAV) using the in vitro human nasal epithelial cell (hNEC) model. Utilizing the hNEC infection model, we assessed the protective effects of HPMC in pH 3.5 and pH 7 buffers against RV and IAV. Acidic and pH-neutral buffers and HPMC dissolved in acidic and pH-neutral buffers were administered for 4 h prior to virus infection and at 4 h post-infection (hpi). The apical supernatant was harvested at 24 hpi to determine the viral loads of RV and IAV (H1N1 and H3N2). HPMC was demonstrated to exert protective effects in the infected hNECs independent of acidic pH. Pre-treatment with HPMC in acidic buffer significantly diminished viral loads for both RV and IAV infections of hNECs. Similarly, direct treatment of HPMC in acidic buffer after infection (4 hpi) also effectively decreased viral loads of both RV and IAV. Moreover, treatment using HPMC in acidic buffer before or after infection did not affect the epithelial integrity and ciliary function of hNECs. This study demonstrates the protective effects of HPMC in acidic buffer against RV and IAV infections of the human nasal epithelium. Full article

Acute respiratory viral infections (ARIs) represent a significant global health challenge, contributing heavily to worldwide morbidity and mortality rates. Recent efforts to combat ARIs have focused on developing nasal spray formulations that effectively target the nasal mucosa. However, challenges such as irritation, discomfort, and safety concerns highlight the need for natural, eco-friendly ingredients. In this study, we evaluated the efficacy of solubilized sturgeon oil (SSO), prepared as an oil-in-water nanoemulsion from Siberian sturgeon, as an eco-friendly preventive nasal spray agent against ARIs. Intranasal pre-treatment with SSO effectively inhibited respiratory infections caused by SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV). Additionally, it suppressed viral replication in both nasal and lung tissues. This antiviral effect was linked to reduced pulmonary inflammation, characterized by decreased infiltration of Ly-6C⁺ monocytes and Ly-6G⁺ neutrophils, along with lower pro-inflammatory cytokine levels. Histopathological analyses confirmed that nasal SSO administration significantly mitigated lung inflammation progression caused by viral infections. Notably, the protective effects of SSO against SARS-CoV-2, IAV, and RSV persisted for at least six hours following nasal application. These findings highlight SSO as a promising eco-friendly and safe candidate for nasal spray formulations, providing a potential frontline defense against ARIs. Full article

Airborne transmission has been implicated as a major route for the spread of microorganisms, causing infectious disease outbreaks worldwide. This has been emphasized by the recent COVID-19 pandemic, caused by the SARS-CoV-2 virus. There is thus an unmet need to develop technologies that arrest the spread of airborne infectious diseases by inactivating viruses in the air. In this study, the efficacy of two commercially available air ionizer systems for inactivating the bacteriophage MS2, which has been utilized as a surrogate of SARS-CoV-2 as well as a surrogate of noroviruses, was assessed. An experimental test apparatus similar to an HVAC duct system was utilized for the efficacy testing. Each of the two ionizer devices was challenged with viral aerosols of the bacteriophage MS2. The results indicate that the two ionizers were able to reduce the concentration of bacteriophage MS2 virus in the air by 82.02% and 81.72%, respectively. These results point to the efficacy of these ionizer devices in inactivating airborne microorganisms and thus making them an important tool in arresting the spread of infectious diseases. More studies are needed to assess their efficacy against other important airborne viruses such as influenza and strains of the SARS-CoV-2 virus. Full article