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Coronaviruses (CoVs) are a class of respiratory viruses with the potential to cause severe respiratory diseases by infecting cells of the upper respiratory tract, bronchial epithelium, and lung. The airway cilia are distributed on the surface of respiratory epithelial cells, forming the first point of contact between the host and the inhaled coronaviruses. The function of the airway cilia is to oscillate and sense, thereby defending against and removing pathogens to maintain the cleanliness and patency of the respiratory tract. Following infection of the respiratory tract, coronaviruses exploit the cilia to invade and replicate in epithelial cells while also damaging the cilia to facilitate the spread and exacerbation of respiratory diseases. It is therefore imperative to investigate the interactions between coronaviruses and respiratory cilia, as well as to elucidate the functional mechanism of respiratory cilia following coronavirus invasion, in order to develop effective strategies for the prevention and treatment of respiratory viral infections. This review commences with an overview of the fundamental characteristics of airway cilia, and then, based on the interplay between airway cilia and coronavirus infection, we propose that ciliary protection and restoration may represent potential therapeutic approaches in emerging and re-emerging coronavirus pandemics. [ABSTRACT FROM AUTHOR]

Middle East respiratory syndrome (MERS) is caused by a specific strain of the 6 types of human coronaviruses (HCoV). MERS-CoV has spread unchecked since it was first discovered in Saudi Arabia in 2012. The virus most likely spreads through nosocomial and zoonotic channels. Genetic analyses suggest that bats were the initial hosts and that the disease spread to camels. Person-to-person transmission occurs with varying frequency, being most prevalent in clinical settings and the least common among the general population and among close relatives. Due to the severity of the illness, high fatality rate, potential for epidemic spread, and lack of adequate medical countermeasures, the World Health Organization (WHO) continues to list MERS-CoV as a priority pathogen. While no specific antiviral medicines exist, a combination of antivirals has shown promise in recent clinical trials. Vaccines against MERS-CoV are critically needed and are currently being developed. Early diagnosis and implementing appropriate infection control measures are keys to preventing hospital-associated outbreaks. Preventive measures include avoiding raw or undercooked meats and other animal products, ensuring proper hand hygiene in healthcare settings and around dromedaries, educating the public and healthcare personnel about the disease, and adhering to other recommended practices. Countries with a high prevalence of MERS should adhere to regulations designed to limit the transmission of the virus. The recent spread of MERS-CoV highlights the importance of public awareness regarding the significance of reporting symptoms so that appropriate control measures can be adopted. The narrative review discusses the incidence of MERS, its clinical presentation, potential transmission routes, recent reports, preventative and control measures, and current therapeutic options. [ABSTRACT FROM AUTHOR]

Summary Background Methods Results Conclusions The COVID‐19 pandemic has significantly changed the lifestyle and dietary habits of societies worldwide. The aim of the study was to assess changes in the distribution of fat tissue and skinfold thickness in adolescents (aged 11–15) from Kraków during the COVID‐19 pandemic period.Two cross‐sectional studies conducted in 2020 and 2022 (before and after the pandemic) involved 1662 adolescents from the Kraków population. Skinfold thickness measurements were taken. The trunk adiposity index, limbs‐to‐trunk fat ratio and limbs‐to‐total skinfold ratio were calculated. Statistical analysis employed a two‐way ANOVA, Tukey's HSD test and the Kruskal–Wallis test, depending on the normality of the distribution.Higher skinfold thicknesses were observed in the majority of age groups in both sexes from the 2022 cohort in comparison with the 2020 cohort. Additionally, higher values of the trunk adiposity index and the limbs‐to‐total skinfold ratio in most age groups were observed. However, an inverse trend was observed in the limbs‐to‐trunk fat radio.The introduced restrictions such as lockdown, remote learning, reduced physical activity and changes in dietary habits could have influenced the distribution of fat tissue and skinfold thickness amongst adolescents from Kraków. [ABSTRACT FROM AUTHOR]

Introduction: Oxysterol-binding protein (OSBP) is known for its crucial role in lipid transport, facilitating cholesterol exchange between the Golgi apparatus and endoplasmic reticulum membranes. Despite its established function in cellular processes, its involvement in coronavirus replication remains unclear. Methods: In this study, we investigated the role of OSBP in coronavirus replication and explored the potential of a novel OSBP-binding compound, ZJ-1, as an antiviral agent against coronaviruses, including SARS-CoV-2. We utilized a combination of biochemical and cellular assays to elucidate the interactions between OSBP and SARS-CoV-2 non-structural proteins (Nsps) and other viral proteins. Results: Our findings demonstrate that OSBP positively regulates coronavirus replication. Moreover, treatment with ZJ-1 resulted in reduced OSBP levels and exhibited potent antiviral effects against multiple coronaviruses. Through our investigation, we identified specific interactions between OSBP and SARS-CoV-2 Nsps, particularly Nsp3, Nsp4, and Nsp6, which are involved in doublemembrane vesicle formation--a crucial step in viral replication. Additionally, we observed that Nsp3 a.a.1-1363, Nsp4, and Nsp6 target vesicle-associated membrane protein (VAMP)-associated protein B (VAP-B), which anchors OSBP to the ER membrane. Interestingly, the interaction between OSBP and VAP-B is disrupted by Nsp3 a.a.1-1363 and partially impaired by Nsp6. Furthermore, we identified SARS-CoV-2 orf7a, orf7b, and orf3a as additional OSBP targets, with OSBP contributing to their stabilization. Conclusion: Our study highlights the significance of OSBP in coronavirus replication and identifies it as a promising target for the development of antiviral therapies against SARS-CoV-2 and other coronaviruses. These findings underscore the potential of OSBP-targeted interventions in combating coronavirus infections. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the research was to evaluate the use of teleophthalmology at a university practice during the COVID-19 pandemic, specifically examining precision, effectiveness, and patient satisfaction. Patients and Methods: Telemedicine visits were offered to new and established patients requesting appointments with the Stony Brook University Department of Ophthalmology between March 30 and June 2, 2020. Records from these visits were reviewed for chief complaint, past medical and ocular history, diagnoses, treatment/management, and providers' sub-specialty. Precision was determined by comparing agreement between diagnoses of the telemedicine visit with those of the subsequent in-person visit. The decision to follow up in person was made by the physician and patient. Diagnostic precision as well as progression, improvement, or stability of patients' symptoms were determined by the physician's assessment at follow-up visits. Post-telemedicine visit satisfaction surveys were sent to all patients. Results: Telemedicine visits were offered to 783 patients, 520 (66.4%) of whom accepted. Of these 520 patients, 409 (78.7%) were established and 105 (20.2%) had in-person, follow-up visits. Overall, the diagnostic precision of the follow-up visits was 89.5%. Precision differed significantly across ophthalmologic subspecialties. Of the patients who had in-person follow-up visits, 56.8% remained stable, 32.4% improved, and 10.8% worsened. Established patients presented with more extensive ocular histories/procedures and experienced a higher percentage of worsening symptoms/disease stage compared to new patients. Oculoplastics/orbit was the most prevalent diagnostic subspecialty that worsened. Surveys were sent to all patients completing telemedicine visits, 15.0% of whom responded. Overall satisfaction was 91.9%, although only 23.0% of respondents preferred telemedicine to an in-office visit. Conclusion: Telehealth provides high levels of precision and patient satisfaction for a wide range of ophthalmologic visits, although most patients still prefer in-office examinations. Employing teleophthalmology for follow-up and emergency care may provide patients with an effective alternative during pandemic situations and beyond. Plain Language Summary: Telemedicine involves integration of modern telecommunications technology into medical practice. Over the years, it has demonstrated greater and more widespread utility for different medical specialties, including ophthalmology. As a response to the recent COVID-19 pandemic, the Stony Brook University Department of Ophthalmology provided an option of telemedicine for patients in lieu of in-person eye examinations. In this paper, Stony Brook ophthalmologists report on their experience with teleophthalmology, particularly regarding its utilization, accuracy, effectiveness, precision, and acceptability. The authors examined the records of 520 patients who had telemedicine encounters between March 30 and June 2, 2020. Precision was determined by comparing the initial and final diagnoses of all patients who had an in-person follow-up appointment following a telemedicine visit. Of 105 patients that followed up, precision was determined to be 89.5%. Precision was compared across ophthalmologic subspecialties and found to be statistically similar (p> 0.05). Approximately a third of patients improved, while nearly 11% worsened. Established and oculoplastics patients were more significantly likely to worsen. Surverys were sent out to study patients to gauge their satisfaction with their telemedicine experience. Although satisfaction was nearly 92%, only 23% of patients preferred telemedicine to an in-person physician encounter. The authors conclude that teleophthalmology provides a high level of diagnostic precision and patient satisfaction; nevertheless, most patients prefer in-person physician encounters. Telemedicine may provide an effective alternative to in-person ophthalmology assessments, especially during a pandemic. There appears to be a lesser but potentially useful role for teleophthalmology in a non-pandemic setting. [ABSTRACT FROM AUTHOR]

Outcomes are presented for a multisite retrospective case series, describing a contemporary cohort of 22 immunocompromised patients with persistent coronavirus disease 2019 (COVID-19) polymerase chain reaction positivity who were retreated with antiviral therapy. For those with data available 14 and 30 days after commencement of antiviral therapy, 41% (9 of 22) and 68% (15 of 22), respectively, cleared COVID-19. [ABSTRACT FROM AUTHOR]

Background Coronavirus disease 2019 (COVID-19) continues to cause hospitalizations and severe disease in children and adults. Methods This study compared the risk factors, symptoms, and outcomes of children and adults hospitalized for COVID-19 from March 2020 to May 2023 across age strata at 5 US sites participating in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence consortium. Eligible patients had an upper respiratory swab that tested positive for severe acute respiratory syndrome coronavirus 2 by nucleic acid amplification. Adjusted odds ratios (aOR) of clinical outcomes were determined for children versus adults, for pediatric age strata compared to adolescents (12–17 years), and for adult age strata compared to young adults (22–49 years). Results Of 9101 patients in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence cohort, 1560 were hospitalized for COVID-19 as the primary reason. Compared to adults (22–105 years, n = 675), children (0–21 years, n = 885) were less commonly vaccinated (14.3% vs 34.5%), more commonly infected with the Omicron variant (49.5% vs 26.1%) and had fewer comorbidities (P <.001 for most comparisons), except for lung disease (P =.24). After adjusting for confounding variables, children had significantly lower odds of receiving supplemental oxygen (aOR, 0.57; 95% confidence interval,.35–.92) and death (aOR, 0.011; 95% confidence interval, <.01–.58) compa--red to adults. Among pediatric age strata, adolescents 12–17 years had the highest odds of receiving supplemental oxygen, high-flow oxygen, and ICU admission. Among adults, those 50–64 years had the highest odds of mechanical ventilation and ICU admission. Conclusions Clinical outcomes of COVID-19 differed across pediatric and adult age strata. Adolescents experienced the most severe disease among children, whereas adults 50–64 years experienced the most severe disease among adults. [ABSTRACT FROM AUTHOR]

The future of the COVID pandemic and its public health and societal impact will be determined by the profile and spread of emerging variants and the timely identification and response to them. Wastewater surveillance of SARS-CoV-2 has been widely adopted in many countries across the globe and has played an important role in tracking infection levels and providing useful epidemiological information that cannot be adequately captured by clinical testing alone. However, novel variants can emerge rapidly, spread globally, and markedly alter the trajectory of the pandemic, as exemplified by the Delta and Omicron variants. Most mutations linked to the emergence of new SARS-CoV-2 variants are found within variable regions of the SARS-CoV-2 Spike protein. We have developed a duplex hemi-nested PCR method that, coupled with short amplicon sequencing, allows simultaneous typing of two of the most highly variable and informative regions of the Spike gene: the N-terminal domain and the receptor binding motif. Using this method in an operationalized public health program, we identified the first known incursion of Omicron BA.1 into Victoria, Australia and demonstrated how sensitive amplicon sequencing methods can be combined with wastewater surveillance as a relatively low-cost solution for early warning of variant incursion and spread. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new emerging coronavirus that caused coronavirus disease 2019 (COVID-19). Whole-genome tracking of SARS-CoV-2 enhanced our understanding of the mechanism of the disease, control, and prevention of COVID-19. Methods: we analyzed 3368 SARS-CoV-2 protein sequences from Iran and compared them with 15.6 million global sequences in the GISAID database, using the Wuhan-Hu-1 strain as a reference. Results: Our investigation revealed that NSP12-P323L, ORF9c-G50N, NSP14-I42V, membrane-A63T, Q19E, and NSP3-G489S were found to be the most frequent mutations among Iranian SARS-CoV-2 sequences. Furthermore, it was observed that more than 94% of the SARS-CoV-2 genome, including NSP7, NSP8, NSP9, NSP10, NSP11, and ORF8, had no mutations when compared to the Wuhan-Hu-1 strain. Finally, our data indicated that the ORF3a-T24I, NSP3-G489S, NSP5-P132H, NSP14-I42V, envelope-T9I, nucleocapsid-D3L, membrane-Q19E, and membrane-A63T mutations might be responsible factors for the surge in the SARS-CoV-2 Omicron variant wave in Iran. Conclusions: real-time genomic surveillance is crucial for detecting new SARS-CoV-2 variants, updating diagnostic tools, designing vaccines, and understanding adaptation to new environments. [ABSTRACT FROM AUTHOR]

The innate immune system serves as the first line of defense against β-coronaviruses (β-CoVs), a family of viruses that includes SARS-CoV-2. Viral sensing via pattern recognition receptors triggers inflammation and cell death, which are essential components of the innate immune response that facilitate viral clearance. However, excessive activation of the innate immune system and inflammatory cell death can result in uncontrolled release of proinflammatory cytokines, resulting in cytokine storm and pathology. PANoptosis, innate immune, inflammatory cell death initiated by innate immune sensors and driven by caspases and RIPKs through PANoptosome complexes, has been implicated in the pathology of viral infections. Therefore, understanding the molecular mechanisms regulating PANoptosis in response to β-CoV infection is critical for identifying new therapeutic targets that can mitigate disease severity. In the current study, we analyzed findings from a cell death-based CRISPR screen with archetypal β-CoV mouse hepatitis virus (MHV) as the trigger to characterize host molecules required for inflammatory cell death. As a result, we identified SMARCA4, a chromatin regulator, as a putative host factor required for PANoptosis in response to MHV. Furthermore, we observed that gRNA-mediated deletion of Smarca4 inhibited MHV-induced PANoptotic cell death in macrophages. These findings have potential translational and clinical implications for the advancement of treatment strategies for β-CoVs and other infections. [ABSTRACT FROM AUTHOR]

The interaction between SARS-CoV PDZ-binding motifs (PBMs) and cellular PDZs is responsible for virus virulence. The PBM sequence present in the 3a and envelope (E) proteins of SARS-CoV can potentially bind to over 400 cellular proteins containing PDZ domains. The role of SARS-CoV 3a and E proteins was studied. SARS-CoVs, in which 3a-PBM and E-PMB have been deleted (3a-PBM-/E-PBM-), reduced their titer around one logarithmic unit but still were viable. In addition, the absence of the E-PBM and the replacement of 3a-PBM with that of E did not allow the rescue of SARS-CoV. E protein PBM was necessary for virulence, activating p38-MAPK through the interaction with Syntenin-1 PDZ domain. However, the presence or absence of the homologous motif in the 3a protein, which does not bind to Syntenin-1, did not affect virus pathogenicity. Mutagenesis analysis and in silico modeling were performed to study the extension of the PBM of the SARS-CoV E protein. Alanine and glycine scanning was performed revealing a pair of amino acids necessary for optimum virus replication. The binding of E protein with the PDZ2 domain of the Syntenin-1 homodimer induced conformational changes in both PDZ domains 1 and 2 of the dimer. [ABSTRACT FROM AUTHOR]

Moringa oleifera (M. oleifera) is a plant widely used for its beneficial properties both in medical and non-medical fields. Because they produce bioactive metabolites, plants are a major resource for drug discovery. In this study, two different cultivars of leaves of M. oleifera (Salento and Barletta) were obtained by maceration or microwave-assisted extraction (MAE). We demonstrated that extracts obtained by MAE exhibited a lower cytotoxic profile compared to those obtained by maceration at concentrations ranged from 25 to 400 µg/mL, on both Vero CCL-81 and Vero/SLAM cells. We examined their antiviral properties against two viruses, i.e., the human coronavirus 229E (HCoV-229E) and measles virus (MeV), which are both responsible for respiratory infections. The extracts were able to inhibit the infection of both viruses and strongly prevented their attack and entry into the cells in a range of concentrations from 50 to 12 µg/mL. Particularly active was the variety of Salento that registered a 50% inhibitory concentration (IC50) at 21 µg/mL for HCoV-229E and at 6 µg/mL for MeV. We identified the presence of several compounds through high performance liquid chromatography (HPLC); in particular, chlorogenic and neochlorogenic acids, quercetin 3-O-β-d-glucopyranoside (QGP), and glucomoringin (GM) were mainly observed. In the end, M. oleifera can be considered a promising candidate for combating viral infections with a very strong action in the early stages of viral life cycle, probably by destructuring the viral particles blocking the virus–cell fusion. [ABSTRACT FROM AUTHOR]

Introduction: New tools have been developed to distinguish the COVID‐19 diagnosis from other viral infections presenting similar symptomatology and mitigate the lack of sensitivity of molecular testing. We previously identified a specific "sandglass" aspect on the white blood cells (WBC) scattergram of COVID‐19 patients, as a highly reliable COVID‐19 screening test (sensitivity: 85.9%, specificity: 83.5% and positive predictive value: 94.3%). We then decided to validate our previous data in a multicentric study. Methods: This retrospective study involved 817 patients with flu‐like illness, among 20 centers, using the same CBC instrument (XN analyzer, SYSMEX, Japan). After training, one specialist per center independently evaluated, under the same conditions, the presence of the "sandglass" aspect of the WDF scattergram, likely representing plasmacytoid lymphocytes. Results: Overall, this approach showed sensitivity: 59.0%, specificity: 72.9% and positive predictive value: 77.7%. Sensitivity improved with subgroup analysis, including in patients with lymphopenia (65.2%), patients presenting symptoms for more than 5 days (72.3%) and in patients with ARDS (70.1%). COVID‐19 patients with larger plasmacytoid lymphocyte cluster (>15 cells) more often have severe outcomes (70% vs. 15% in the control group). Conclusion: Our findings confirm that the WBC scattergram analysis could be added to a diagnostic algorithm for screening and quickly categorizing symptomatic patients as either COVID‐19 probable or improbable, especially during COVID‐19 resurgence and overlapping with future influenza epidemics. The observed large size of the plasmacytoid lymphocytes cluster appears to be a hallmark of COVID‐19 patients and was indicative of a severe outcome. Furthers studies are ongoing to evaluate the value of the new hematological parameters in combination with WDF analysis. [ABSTRACT FROM AUTHOR]

Food retail businesses experienced a pronounced increase in sales when food hospitality outlets closed in the early stages of the COVID-19 pandemic in Canada. This study investigates how pandemic-related modifications to food retail businesses in Ontario, Canada affected the well-being of workers. Semi-structured interviews were conducted with 17 food retail employees between June 2020 and May 2021 as part of the Food Retail Environment Study for Health and Economic Resiliency (FRESHER). Transcripts were analyzed inductively, and themes were refined using the Effort Reward Imbalance Model. Themes were connected to the main components of this model: extrinsic effort, intrinsic effort, money, esteem, status control, and burnout. Results indicate that, for food retail employees, the presence of an imbalance between efforts and rewards threatens well-being via symptoms of burnout. Further study is needed to examine how this inequality and burnout among this population might be measured and addressed. [ABSTRACT FROM AUTHOR]

Background The role of children and staff in SARS-CoV-2 transmission outside and within households is still not fully understood when large numbers are in regular, frequent contact in schools. Methods We used the self-controlled case-series method during the alpha- and delta-dominant periods to explore the incidence of infection in periods around a household member infection, relative to periods without household infection, in a cohort of primary and secondary English schoolchildren and staff from November 2020 to July 2021. Results We found the relative incidence of infection in students and staff was highest in the 1–7 days following household infection, remaining high up to 14 days after, with risk also elevated in the 6–-12 days before household infection. Younger students had a higher relative incidence following household infection, suggesting household transmission may play a more prominent role compared with older students. The relative incidence was also higher among students in the alpha variant dominant period. Conclusions This analysis suggests SARS-CoV2 infection in children, young people and staff at English schools were more likely to be associated with within-household transmission than from outside the household, but that a small increased risk of seeding from outside is observed. [ABSTRACT FROM AUTHOR]

The outbreak of the Covid-19 pandemic led to various scholarly studies both from scientific and linguistic repertoires. This study is a pragmatic analysis of news reports on Coronavirus from selected national and international newspapers from the point of view of Austin (1962) and Searle's (1969) Speech Act Theory. A total of 40 utterances were purposively sampled from the four newspapers (Vanguard, Daily Sun, The New York Times and The Guardian). Qualitative research design was used for the data analysis. The qualitative analysis discussed the aspects of the Speech Act Theory: locutionary, illocutionary and perlocutionary. From the analysis, it is obvious that the newspaper media used more of assertives, as they majorly report, inform and assert the state of affairs in their reports on covid-19. [ABSTRACT FROM AUTHOR]

The public health response to the COVID-19 pandemic may have changed leisure-time physical activity (PA) behaviour, as many 'Stay-at-Home' policies mandated closure of indoor recreational facilities. This study examined changes in adult leisure-time PA in more and less active groups during and after COVID-19 restrictions in a relatively active region where outdoor PA was not limited. Self-reported data on walking, moderate, and vigorous PA before, during, and after restrictions were collected via a retrospective internet survey with convenience and snowball sampling. Respondents (N = 183) were categorised as either meeting (n = 129) or not meeting (n = 54) the national recommendation of 150 minutes/week of moderate-to-vigorous aerobic PA (MVPA) during the period before restrictions. Minutes of walking, MVPA, and total PA were compared across groups and periods with two-way repeated-measure ANOVAs. Those who met PA guidelines decreased MVPA by 51.0 minutes/week during restrictions compared to before. Those not meeting PA guidelines increased total PA by 88.1 minutes/week during restrictions. This study highlights a need to better understand interactions between built environment and social cognitive factors related to leisure-time PA, which may help inform future PA interventions. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is frequently associated with thrombo inflammation, which can predispose to developing of life-threatening conditions in children such as the multisystem inflammatory syndrome (MIS-C) and Kawasaki disease. Because of the consistent overlap in pathogenesis and symptoms, identifying laboratory tests that may aid in the differential diagnosis of these pathologies becomes crucial. We performed an electronic search in PubMed, Web of Science and Scopus, without date or language restrictions, to identify all possible studies reporting D-dimer values in separate cohorts of children with MIS-C or Kawasaki disease. Three multicenter cohort studies were included in our analysis, totaling 487 patients (270 with MIS-C and 217 with Kawasaki disease). In this meta-analysis, significantly higher D-dimer values were found in MIS-C compared to Kawasaki disease in all three studies, yielding an SMD of 1.5 (95 % CI, 1.3–1.7) mg/L. Thus, very high D-dimer values early in the course of disease should raise the clinical suspicion of MIS-C rather than Kawasaki disease. Further studies should be planned to identify harmonized D-dimer diagnostic thresholds that may help discriminate these conditions. [ABSTRACT FROM AUTHOR]

Many aspects of the life cycle and genetics of (+)RNA viruses are directed by their genome replication organelles (ROs), which form as spherular membrane invaginations (this review's primary focus) or double-membrane vesicles. Recent cryo-electron microscopy (cryo-EM) studies have transformed understanding of RO structure and assembly. RO membrane vesicles containing dsRNA replication intermediates are gated to the cytosol by ringed 'crown' complexes of viral RNA replication proteins that direct synthesis, 5′ capping, and release of new mRNA-sense genomic and subgenomic RNAs. Although nodaviruses and alphaviruses are only distantly related, their RO crowns conserve 12-fold symmetry, key enzymatic and structural motifs, and multistage assembly. Continuing studies should enable new antiviral controls and reveal how crown assembly steps are coupled to viral (−)RNA and (+)RNA synthesis, RO vesicle formation, and progeny RNA transfer to translation, new RO formation, and encapsidation. Positive-strand RNA [(+)RNA] viruses include pandemic SARS-CoV-2, tumor-inducing hepatitis C virus, debilitating chikungunya virus (CHIKV), lethal encephalitis viruses, and many other major pathogens. (+)RNA viruses replicate their RNA genomes in virus-induced replication organelles (ROs) that also evolve new viral species and variants by recombination and mutation and are crucial virus control targets. Recent cryo-electron microscopy (cryo-EM) reveals that viral RNA replication proteins form striking ringed 'crowns' at RO vesicle junctions with the cytosol. These crowns direct RO vesicle formation, viral (−)RNA and (+)RNA synthesis and capping, innate immune escape, and transfer of progeny (+)RNA genomes into translation and encapsidation. Ongoing studies are illuminating crown assembly, sequential functions, host factor interactions, etc., with significant implications for control and beneficial uses of viruses. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic disparities play an important role in disease epidemiology and outcomes in pregnancy. Objective: The objective was to evaluate whether pregnant women with COVID-19 living in a food desert, are at increased risk of more severe disease reflected by symptoms at presentation and need for hospitalization. Methods: In this retrospective observational study, the electronic medical records of all pregnant patients with documented SARS-CoV-2 infection were reviewed. Food deserts were defined by the USDA and the patient's residence was mapped on the Food Access Research Atlas to determine whether each patient lived within a food desert. Comparisons between those with documented symptomatic COVID-19 required hospitalization to those with documented COVID-19 without need for hospitalization were made using univariate analysis and multivariable logistic regression analysis. Results: The cohort consisted of 129 pregnant patients with COVID-19, with 59.7% (n = 77) asymptomatic and 33.3% (n = 43) requiring admission due to disease severity. The majority were Hispanic (70.5%), and obese (median BMI 31.91 kg/m2), with 33.3% living in a food desert. Patients with disease severity necessitating admission were significantly more likely to reside in a food desert (46.5% vs. 27.9%, P 0.037, OR 2.246, 95% CI 1.048–4.814). No other significant differences were identified on univariate. Multivariable binary logistic regression modeling confirmed food desert residence to be the only independent predictor of more severe COVID-19. Conclusion for Practice: There is a strong association between living in a food desert and the development of symptomatic COVID-19 requiring hospitalization in pregnancy. Significance: What is already known on this subject?: Food deserts reflect socioeconomic disparities that affect the health of pregnant women. Those that reside in a food desert have an overall increase in pregnancy morbidity. In addition, current understanding has demonstrated that pregnant women are at increased risk of severe COVID-19 infection. What this study adds?: In pregnancy, COVID-19 disproportionally affects those who reside in a food desert locale with more severe infection, reflecting the existence of health disparities in an urban community. [ABSTRACT FROM AUTHOR]

In late 2019, the emergence of a novel coronavirus led to its identification as SARS-CoV-2, precipitating the onset of the COVID-19 pandemic. Many experimental and computational studies were performed on SARS-CoV-2 to understand its behavior and patterns. In this research, Molecular Dynamic (MD) simulation is utilized to compare the behaviors of SARS-CoV-2 and its Variants of Concern (VOC)-Alpha, Beta, Gamma, Delta, and Omicron-with the hACE2 protein. Protein structures from the Protein Data Bank (PDB) were aligned and trimmed for consistency using Chimera, focusing on the receptor-binding domain (RBD) responsible for ACE2 interaction. MD simulations were performed using Visual Molecular Dynamics (VMD) and Nanoscale Molecular Dynamics (NAMD2), and salt bridges and hydrogen bond data were extracted from the results of these simulations. The data extracted from the last 5 ns of the 10 ns simulations were visualized, providing insights into the comparative stability of each variant's interaction with ACE2. Moreover, electrostatics and hydrophobic protein surfaces were calculated, visualized, and analyzed. Our comprehensive computational results are helpful for drug discovery and future vaccine designs as they provide information regarding the vital amino acids in protein-protein interactions (PPIs). Our analysis reveals that the Original and Omicron variants are the two most structurally similar proteins. The Gamma variant forms the strongest interaction with hACE2 through hydrogen bonds, while Alpha and Delta form the most stable salt bridges; the Omicron is dominated by positive potential in the binding site, which makes it easy to attract the hACE2 receptor; meanwhile, the Original, Beta, Delta, and Omicron variants show varying levels of interaction stability through both hydrogen bonds and salt bridges, indicating that targeted therapeutic agents can disrupt these critical interactions to prevent SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Coronaviruses constitute a global threat to human and animal health. It is essential to investigate the long-distance RNA-RNA interactions that approximate remote regulatory elements in strategies, including genome circularization, discontinuous transcription, and transcriptional enhancers, aimed at the rapid replication of their large genomes, pathogenicity, and immune evasion. Based on the primary sequences and modeled RNA-RNA interactions of two experimentally defined coronaviral enhancers, we detected via an in silico primary and secondary structural analysis potential enhancers in various coronaviruses, from the phylogenetically ancient avian infectious bronchitis virus (IBV) to the recently emerged SARS-CoV-2. These potential enhancers possess a core duplex-forming region that could transition between closed and open states, as molecular switches directed by viral or host factors. The duplex open state would pair with remote sequences in the viral genome and modulate the expression of downstream crucial genes involved in viral replication and host immune evasion. Consistently, variations in the predicted IBV enhancer region or its distant targets coincide with cases of viral attenuation, possibly driven by decreased open reading frame (ORF)3a immune evasion protein expression. If validated experimentally, the annotated enhancer sequences could inform structural prediction tools and antiviral interventions. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To recognise the need to proactively address the barriers to accessing healthcare that people with learning disabilities may experience • To learn about the development of a desensitisation programme for people with learning disabilities and a fear of needles to support them to receive the coronavirus disease 2019 (COVID-19) vaccine • To consider interventions that you could implement in your practice to support people with learning disabilities to access healthcare interventions. Many people with learning disabilities have a fear of needles and as a result they find receiving injections and vaccinations challenging. Therefore, community learning disability nurses and positive behaviour support practitioners developed a desensitisation programme with the aim of supporting people with learning disabilities who had a needle phobia to receive coronavirus disease 2019 (COVID-19) vaccines. Additionally, reasonable adjustments were made for five individuals who did not have a fear of needles but required a home visit with familiar healthcare professionals who they felt comfortable with. Of the 24 people who engaged in the desensitisation programme, 88% (n=21) received all doses of the COVID-19 vaccine, while 80% (n=4) of five people who were provided with reasonable adjustments received all doses of the COVID-19 vaccine. This article discusses how and why the desensitisation programme was developed, what worked well, the challenges encountered and other areas where the approaches used could be implemented to support people with learning disabilities with accessing other healthcare interventions. [ABSTRACT FROM AUTHOR]

This paper proposes a hybrid Modified Coronavirus Herd Immunity Aquila Optimization Algorithm (MCHIAO) that compiles the Enhanced Coronavirus Herd Immunity Optimizer (ECHIO) algorithm and Aquila Optimizer (AO). As one of the competitive human-based optimization algorithms, the Coronavirus Herd Immunity Optimizer (CHIO) exceeds some other biological-inspired algorithms. Compared to other optimization algorithms, CHIO showed good results. However, CHIO gets confined to local optima, and the accuracy of large-scale global optimization problems is decreased. On the other hand, although AO has significant local exploitation capabilities, its global exploration capabilities are insufficient. Subsequently, a novel metaheuristic optimizer, Modified Coronavirus Herd Immunity Aquila Optimizer (MCHIAO), is presented to overcome these restrictions and adapt it to solve feature selection challenges. In this paper, MCHIAO is proposed with three main enhancements to overcome these issues and reach higher optimal results which are cases categorizing, enhancing the new genes' value equation using the chaotic system as inspired by the chaotic behavior of the coronavirus and generating a new formula to switch between expanded and narrowed exploitation. MCHIAO demonstrates it's worth contra ten well-known state-of-the-art optimization algorithms (GOA, MFO, MPA, GWO, HHO, SSA, WOA, IAO, NOA, NGO) in addition to AO and CHIO. Friedman average rank and Wilcoxon statistical analysis (p-value) are conducted on all state-of-the-art algorithms testing 23 benchmark functions. Wilcoxon test and Friedman are conducted as well on the 29 CEC2017 functions. Moreover, some statistical tests are conducted on the 10 CEC2019 benchmark functions. Six real-world problems are used to validate the proposed MCHIAO against the same twelve state-of-the-art algorithms. On classical functions, including 24 unimodal and 44 multimodal functions, respectively, the exploitative and explorative behavior of the hybrid algorithm MCHIAO is evaluated. The statistical significance of the proposed technique for all functions is demonstrated by the p-values calculated using the Wilcoxon rank-sum test, as these p-values are found to be less than 0.05. [ABSTRACT FROM AUTHOR]

The global pandemic has disrupted virtually all countries on health, psychological functioning, and economies, to name a few. Accurate information has also fallen victim to the pandemic, which has been rife with misinformation and conspiracy theories. The current study investigated Covid-19 deceptions related to employment. With complete anonymity via MTurk, 389 participants from the United States rated their likelihood of deception regarding hypothetical four workplace scenarios. The first set of analyses examined differences between high and low risk of deceptions for each scenario based on participants' self-appraisals. The largest differences were found for general conspiracy beliefs and affective disorders, specifically major depression and generalized anxiety. The second set of analyses focused across the workplace scenarios on two operationalized groups with Likely-Deceptive (n = 189) vastly outnumbering Likely-Genuine (n = 55). Personal experiences with Covid-19 dramatically increased deceptions. Testing positive for Covid-19 increased the odds of being in the Likely-Deceptive by twelve-fold. Two discriminant models examined cognitive misbeliefs and psychological functioning. When both were combined, depression and Covid-19 misinformation produced the strongest structure coefficients followed closely by general conspiracy beliefs and generalized anxiety. The far-ranging implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Early in the COVID-19 pandemic, studies documented a marked decline in mental health and well-being when compared with prepandemic levels. This study examined how different coping styles were associated with anxiety, depression, and sleep problems among U.S. adults March–April 2020 during the COVID-19 pandemic. Data from 535 U.S. adults across three time points were analyzed using longitudinal multilevel logistic and linear regression modeling. Avoidant-emotional coping was associated with greater odds of experiencing anxiety (OR = 1.65, p <.001). Both avoidant- and active-emotional coping were associated with greater odds of experiencing depression (OR = 1.67, p <.001, and OR = 1.09, p =.022, respectively) and sleep problems (b = 0.05, p <.001, and b = 0.01, p =.005, respectively). Alternatively, problem-focused coping was associated with lower odds of depression (OR = 0.86, p <.001). Results converge with previous evidence suggesting the perniciousness of avoidant-emotional coping during the pandemic, but also underscore that problem-focused coping strategies may represent one important source of resilience for adults to adapt despite such challenges. [ABSTRACT FROM AUTHOR]

This study introduces the nanobromhexine lipid particle (NBL) platform designed for effective pulmonary drug delivery. Inspired by respiratory virus transport mechanisms, NBL address challenges associated with mucus permeation and inflammation in pulmonary diseases. Composed of low molecular weight polyethylene glycol-coated lipid nanoparticles with bromhexine hydrochloride, NBL exhibit a size of 118 ± 24 nm, a neutral zeta potential, osmolarity of 358 ± 28 mOsmol/kg, and a pH of 6.5. Nebulizing without leakage and showing no toxicity to epithelial cells, NBL display mucoadhesive properties with a 60% mucin-binding efficiency. They effectively traverse the dense mucus layer of Calu-3 cultures in an air-liquid interface, as supported by a 55% decrease in MUC5AC density and a 29% increase in nanoparticles internalization compared to non-exposed cells. In assessing immunomodulatory effects, NBL treatment in SARS-CoV-2-infected lung cells leads to a 40-fold increase in anti-inflammatory MUC1 gene expression, a proportional reduction in pro-inflammatory IL-6 expression, and elevated anti-inflammatory IL-10 expression. These findings suggest a potential mechanism to regulate the excessive IL-6 expression triggered by virus infection. Therefore, the NBL platform demonstrates promising potential for efficient pulmonary drug delivery and immunomodulation, offering a novel approach to addressing mucus permeation and inflammation in pulmonary diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Data on characteristics and outcomes of coronavirus (COVID)-19 patients complicated with arterial thrombosis (AT) are scarce. Therefore, we carried out a systematic review (PRISMA, PROSPERO statements; PubMed, Scopus, and Web of Science) to identify risk factors, clinical presentation, treatment, and outcomes. We included publications from December 2019 to October 2020. Groups: (a) ischemic stroke, (b) thrombotic storm, (c) peripheral vascular thrombosis, (d) myocardial infarction, and (e) left cardiac thrombus or in-transit thrombus (venous system thrombus floating or attaching to the right heart). We considered 131 studies. The most frequent cardiovascular risk factors were: hypertension, diabetes, and dyslipidemia. A high proportion presented with asymptomatic, mild, or moderate COVID-19 (n = 91, 41.4%). We identified a high percentage of isolated ischemic stroke and thrombotic storm. Groups with higher mortality rate: intracardiac thrombus (1/2, 50.0%), thrombotic storm (18/49, 36.7%), and ischemic stroke (48/131, 36.6%). A small number received thromboprophylaxis. Most patients received antithrombotic treatment. The most frequent bleeding complication was intracranial hemorrhage, primarily with isolated stroke. Overall mortality was 33.6% (74/220). Despite a wide range of COVID-19 severity, a high proportion had AT as a complication of non-severe disease. AT can affect different vascular territories; mortality is associated with stroke, intensive care unit stay, and severe COVID-19. [ABSTRACT FROM AUTHOR]

Patients who undergo metabolic and bariatric surgery (MBS) are at risk for thromboembolism. Patients are susceptible to coronavirus throughout the perioperative period, which also has a well-known association with thrombotic complications. To identify and define the association between venous thromboembolism (VTE) and postoperative coronavirus diagnosis in bariatric surgery patients. United States. We conducted a retrospective cohort study using the MBS Accreditation and Quality Improvement Program (MBSAQIP) 2021 database to analyze the incidence of VTE within 30 days of surgery. VTE was a composite variable defined as either postoperative pulmonary embolism or postoperative venous thrombus requiring treatment. Cohorts were stratified by whether the patient was diagnosed with postoperative coronavirus. We created a multivariable logistic regression model to determine the adjusted odds of postoperative VTE based on various factors. Additionally, we conducted subset analyses of sleeve gastrectomy and Roux-en-Y bypass cases, the 2 most frequent bariatric operations in the United States. Patients diagnosed with postoperative coronavirus were significantly more likely to develop postoperative VTE (1.1% versus.3%, P <.001). In our logistic regression model, the adjusted odds of postoperative VTE for patients with postoperative coronavirus was 3.55 (95% CI: 2.15–5.87, P <.001). For patients who underwent Roux-en-Y bypass, the adjusted odds was even greater at 5.69 (95% CI: 2.76–11.70, P <.001). Early postoperative coronavirus infection after MBS is associated with higher odds of postoperative VTE. This persisted on subset analyses of the 2 most common procedures and appeared particularly important for Roux-en-Y bypass. COVID infection after MBS may warrant prolonged VTE prophylaxis. • Postoperative COVID was associated with VTE development in MBS patients. • This association persisted on multivariable logistic regression analysis. • There was no difference in mortality in patients with and without postop COVID diagnosis. [ABSTRACT FROM AUTHOR]

Human life has faced fundamental challenges in many aspects due to the spread ofthe Coronavirus disease in the world, resulting in rethinking urban design and planning policies and theories to make cities more resilient and healthier. Numerous studies have been conducted in this field due to the pivotal role of the built environment in improving public health. The present study aims to assess the role of the influential components of the built environment in the outbreak of Covid-19 by conducting a systematic literature review. The studies were searched through the Scopus database and screened and reviewed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Totally, 145 studies among 13,002 met the predetermined criteria. The results were expressed in 11 themes including mobility, density, soundscape, public spaces, green spaces, housing, land use, socio-economic qualities, environmental qualities, tourism, and smartness. [ABSTRACT FROM AUTHOR]

In this article, a comprehensive methodology has been used to investigate the policies and measures taken around the world in the fight against the Covid-19 pandemic. Research includes examining international reports, official government statements, and scientific literature from organizations such as the World Health Organization (WHO). Analysis and synthesis of these resources were made to identify common trends, challenges and effective strategies used in different countries and regions. The methodology aims to provide a comprehensive overview of the global response to the Covid-19 pandemic, to provide insights into the effectiveness of these various policies and measures by addressing the measures taken and policies implemented in response to the COVID-19 pandemic. Then, he discussed the countries struggling with the covid-19 pandemic on a country basis and explained the policies and measures they took. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome caused by a coronavirus is a recent viral infection. There is no scientific evidence or clinical trials to indicate that possible therapies have demonstrated results in suspected or confirmed patients. This work aims to perform a virtual screening of 1430 ligands through molecular docking and to evaluate the possible inhibitory capacity of these drugs about the Mpro protease of Covid-19. The selected drugs were registered with the FDA and available in the virtual drug library, widely used by the population. The simulation was performed using the MolAiCalD algorithm, with a Lamarckian genetic model (GA) combined with energy estimation based on rigid and flexible conformation grids. In addition, molecular dynamics studies were also performed to verify the stability of the receptor-ligand complexes formed through analyses of RMSD, RMSF, H–Bond, SASA, and MMGBSA. Compared to the binding energy of the synthetic redocking coupling (−6.8 kcal/mol/RMSD of 1.34 Å), which was considerably higher, it was then decided to analyze the parameters of only three ligands: ergotamine (−9.9 kcal/mol/RMSD of 2.0 Å), dihydroergotamine (−9.8 kcal/mol/RMSD of 1.46 Å) and olysio (−9.5 kcal/mol/RMSD of 1.5 Å). It can be stated that ergotamine showed the best interactions with the Mpro protease of Covid-19 in the in silico study, showing itself as a promising candidate for treating Covid-19. [ABSTRACT FROM AUTHOR]

Vacuole membrane protein 1 (VMP1) is an integral membrane protein that plays a pivotal role in cellular processes, particularly in the regulation of autophagy. Autophagy, a self-degradative mechanism, is essential for maintaining cellular homeostasis by degradation and recycling damaged organelles and proteins. VMP1 involved in the autophagic processes include the formation of autophagosomes and the subsequent fusion with lysosomes. Moreover, VMP1 modulates endoplasmic reticulum (ER) calcium levels, which is significant for various cellular functions, including protein folding and cellular signaling. Recent studies have also linked VMP1 to the cellular response against viral infections and lipid droplet (LD). Dysregulation of VMP1 has been observed in several pathological conditions, including neurodegenerative diseases such as Parkinson's disease (PD), pancreatitis, hepatitis, and tumorogenesis, underscoring its potential as a therapeutic target. This review aims to provide an overview of VMP1's multifaceted roles and its implications in disease pathology. [ABSTRACT FROM AUTHOR]

Coronaviruses are widespread in mammals and birds, causing mostly digestive and respiratory problems. In cats, feline coronaviruses undergo mutations while replicating, giving rise to the fatal coronavirus causing the feline infectious peritonitis (FIP) disease. Several mutations in viral genes, among them 3c and M, are involved in the development of FIP. In order to study these viral shifts, samples of 43 organs, feces, and ascites collected from cats showing clinical signs of feline infectious peritonitis were tested, and the sequences obtained for the 3c and M genes were analyzed. The 3c gene nucleotides showed truncations commonly observed in feline infectious peritonitis virus. Additionally, the sequences corresponding to the 3c genes obtained from different organs of the same individual displayed high similarities, supporting the internal mutation theory. The analyses of the M gene and putative polypeptides showed similarities with canine coronaviruses, supporting the recombination theory between feline and canine coronaviruses. Infectious coronaviral strains are still challenging because of the difficulty in obtaining an effective vaccine for their prevention, and also because of the limited alternatives for therapy of FIP in cats. [ABSTRACT FROM AUTHOR]

Goal: Analysis of the results of thrombectomy from the arteries of the lower extremities in patients with COVID-19 against the background of different severity of respiratory failure. Materials and Methods: This retrospective, cohort, comparative study for the period from 05/01/2022 to 20/07/2022 included 305 patients with acute thrombosis of the arteries of the lower extremities against the background of the course of COVID-19 (SARS-CoV-2 Omicron variant). Depending on the type of oxygen support, 3 groups of patients were formed: group 1 (n = 168) – oxygen insufflation through nasal cannulas; group 2 (n = 92) – non-invasive lung ventilation; and group 3 (n = 45) – artificial lung ventilation. Results: Myocardial infarction and ischemic stroke were not detected in the total sample. The highest number of deaths (group 1: 5.3%, n = 9; group 2: 72.8%, n = 67; group 3: 100%, n = 45; p < 0.0001), rethrombosis (group 1 : 18.4%, n = 31; group 2: 69.5%, n = 64; group 3: 91.1%, n = 41; p < 0.0001), and limb amputations (group 1: 9.5%, n = 16; group 2: 56.5%, n = 52; group 3: 91.1%, n = 41; p < 0.0001) was recorded in group 3 (ventilated) patients. Conclusion: In patients infected with COVID-19 and on artificial lung ventilation, a more aggressive course of the disease is noted, expressed in an increase in laboratory parameters (C-reactive protein, ferritin, interleukin-6, and D-dimer) of the degree of pneumonia (CT-4 in overwhelming number) and localization of thrombosis of the arteries of the lower extremities, mainly in the tibial arteries. [ABSTRACT FROM AUTHOR]

Pentecostalism, to which the Apostolic Faith Mission in Zimbabwe belongs, is one of the fastest growing brands of Christianity in Zimbabwe. Most Pentecostal churches promise divine health, deliverance, miracles and prosperity to their members. In the Apostolic Faith Mission of Zimbabwe, women constitute the greater percentage of the church membership. Despite the fact that Pentecostal churches make promises of a good life, a church is generally expected to be a safe haven to its members. This paper wished to examine whether the Pentecostal church response to COVID-19 helped to build or destroy the mental health of its majority members, the women. The findings however show that the church mostly affected women's mental health in a negative way as it grappled with the challenges brought about by the COVID-19 pandemic. This article therefore contests the claim of providing a good life as done by some Pentecostal churches. This was a qualitative study and utilized findings from a sample of 15 members of the Apostolic Faith Mission in Zimbabwe who were selected using purposive sampling. The findings suggest that the women were stressed by the teachings on marriage and emphasis on collection of money, discrimination against single women, the prosperity gospel, and patriarchy. [ABSTRACT FROM AUTHOR]

Development of potent and broad‐spectrum drugs against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains one of the top priorities, especially in the cases of the emergence of mutant viruses and inability of current vaccines to prevent viral transmission. In this study, we have generated a novel membrane fusion‐inhibitory lipopeptide IPB29, which is currently under clinical trials; herein, we report its design strategy and preclinical data. First, we surprisingly found that IPB29 with a rigid linker between the peptide sequence and lipid molecule had greatly improved α‐helical structure and antiviral activity. Second, IPB29 potently inhibited a large panel of SARS‐CoV‐2 variants including the previously and currently circulating viruses, such as Omicron XBB.5.1 and EG.5.1. Third, IPB29 could also cross‐neutralize the bat‐ and pangolin‐isolated SARS‐CoV‐2‐related CoVs (RatG13, PCoV‐GD, and PCoV‐GX) and other human CoVs (SARS‐CoV, MERS‐CoV, HCoV‐NL63, and HCoV‐229E). Fourth, IPB29 administrated as an inhalation solution (IPB29‐IS) in Syrian hamsters exhibited high therapeutic and preventive efficacies against SARS‐CoV‐2 Delta or Omicron variant. Fifth, the pharmacokinetic profiles and safety pharmacology of IPB29‐IS were extensively characterized, providing data to support its evaluation in humans. In conclusion, our studies have demonstrated a novel design strategy for viral fusion inhibitors and offered an ideal drug candidate against SARS‐CoV‐2 and other coronaviruses. [ABSTRACT FROM AUTHOR]

Non-structural protein 2 (nsp2) exists in all coronaviruses (CoVs), while its primary function in viral pathogenicity, is largely unclear. One such enteric CoV, porcine epidemic diarrhea virus (PEDV), causes high mortality in neonatal piglets worldwide. To determine the biological role of nsp2, we generated a PEDV mutant containing a complete nsp2 deletion (rPEDV-Δnsp2) from a highly pathogenic strain by reverse genetics, showing that nsp2 was dispensable for PEDV infection, while its deficiency reduced viral replication in vitro. Intriguingly, rPEDV-Δnsp2 was entirely avirulent in vivo, with significantly increased productions of IFNB (interferon beta) and IFN-stimulated genes (ISGs) in various intestinal tissues of challenged newborn piglets. Notably, nsp2 targets and degrades TBK1 (TANK binding kinase 1), the critical kinase in the innate immune response. Mechanistically, nsp2 induced the macroautophagy/autophagy process and recruited a selective autophagic receptor, NBR1 (NBR1 autophagy cargo receptor). NBR1 subsequently facilitated the K48-linked ubiquitination of TBK1 and delivered it for autophagosome-mediated degradation. Accordingly, the replication of rPEDV-Δnsp2 CoV was restrained by reduced autophagy and excess productions of type I IFNs and ISGs. Our data collectively define enteric CoV nsp2 as a novel virulence determinant, propose a crucial role of nsp2 in diminishing innate antiviral immunity by targeting TBK1 for NBR1-mediated selective autophagy, and pave the way to develop a new type of nsp2-based attenuated PEDV vaccine. The study also provides new insights into the prevention and treatment of other pathogenic CoVs. Abbreviations: 3-MA: 3-methyladenine; Baf A1: bafilomycin A1; CoV: coronavirus; CQ: chloroquine; dpi: days post-inoculation; DMVs: double-membrane vesicles; GABARAP: GABA type A receptor-associated protein; GFP: green fluorescent protein; GIGYF2: GRB10 interacting GYF protein 2; hpi: hours post-infection; IFA: immunofluorescence assay; IFIH1: interferon induced with helicase C domain 1; IFIT2: interferon induced protein with tetratricopeptide repeats 2; IFITM1: interferon induced transmembrane protein 1; IFNB: interferon beta; IRF3: interferon regulatory factor 3; ISGs: interferon-stimulated genes; mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAVS: mitochondrial antiviral signaling protein; NBR1: NBR1 autophagy cargo receptor; nsp2: non-structural protein 2; OAS1: 2'-5'-oligoadenylate synthetase 1; PEDV: porcine epidemic diarrhea virus; PRRs: pattern recognition receptors; RIGI: RNA sensor RIG-I; RT-qPCR: reverse transcription quantitative polymerase chain reaction; SQSTM1: sequestosome 1; TBK1: TANK binding kinase 1; TCID50: 50% tissue culture infectious doses; VSV: vesicular stomatitis virus. [ABSTRACT FROM AUTHOR]

Unequivocally, South Africa, amid an environment of paucity of resources, faces the arduous challenge of fighting the scourge of coronavirus. This has necessitated assessing the parenting hurdles experienced during the lockdown in eclectic contexts in South Africa. This article applied a review of the literature methodology. The researchers drew their literature from journal articles, monographs, and book chapters and used informal conversations amid their intuitive and experiential powers. The article established that South African families face parenting hurdles driven by the COVID-19 lockdown due to the following factors: Children and their parents driven to a state of duress; children facing various kinds of mistreatment; pecuniary dimensions; lockdown presenting states of distress to people generally; and a surge of gender-based violence. This article recommends that social service professionals such as psychologists, counsellors, and social workers be on the frontline in discharging various psychotherapeutic education to the communities. These researchers also recommend that the government and other community development practitioners emphasize the application of the tenets of ubuntu as a conflict resolution tool to reduce conflicts and afford the children qualitative parenting. This research provides some interventions for handling parenting during any other disruptions, such as the coronavirus-imposed lockdown. [ABSTRACT FROM AUTHOR]

Copper has well-documented antibacterial effects but few have evaluated it after prolonged use and against bacteria and viruses. Coupons from three copper formulations (solid, thermal coating, and decal applications) and carbon steel controls were subjected to 200 rounds simulated cleaning using a Wiperator™ and either an accelerated hydrogen peroxide, quaternary ammonium, or artificial sweat products. Antibacterial activity against S. aureus and P. aeruginosa was then evaluated using a modified Environmental Protection Agency protocol. Antiviral activity against coronavirus (229E) and norovirus (MNV-1) surrogates was assessed using the TCID50 method. Results were compared to untreated control coupons. One hour after inoculation, S. aureus exhibited a difference in log kill of 1.16 to 4.87 and P. aeruginosa a log kill difference of 3.39–5.23 (dependent upon copper product and disinfectant) compared to carbon steel. MNV-1 demonstrated an 87–99% reduction on each copper surfaces at 1 h and 99% reduction at 2 h compared to carbon steel. Similarly, coronavirus 229E exhibited a 97–99% reduction after 1 h and 90–99% after 2 h. Simulated use with artificial sweat did not hinder the antiviral nor the antibacterial activity of Cu surfaces. Self-sanitizing copper surfaces maintained antibacterial and antiviral activity after 200 rounds of simulated cleaning. [ABSTRACT FROM AUTHOR]

Aim: This paper investigates the effect of a religious holiday (Eid-ul-Fitr in Pakistan) on compliance behaviour instituted during the COVID-19 pandemic. Longstanding religion-based norms of behaviour during the Eid holidays (traveling to meet family members, praying in large gatherings, hugging) may counteract newly established (and weaker) norms of health-preserving behaviours. Method: We study the impact of Eid-ul-Fitr on compliance with COVID guidelines for a sample of university students. Our effects are identified by unprompted delays in fielding a survey measuring compliance with prescribed behaviours. Results: We find that compliance with guidelines declines immediately after the religious holiday in our sample of students, with no observable decline in other well documented predictors of compliance behaviour (risk perceptions, trust in the authorities). We find that this decline in compliance is largely attributable to male participants, with one important exception. We further confirm our results by conducting robustness checks incorporating matching techniques and a smaller follow-up study where we randomize invitations to the survey. Conclusion: We conclude that amid the pandemic, newly formed norms pertaining to healthcare guidelines (focusing on social-distancing) emerged, and were subsequently undercut by longstanding norms of behaviour following a religious celebration: Eid-ul-Fitr. This paper underscores the fragility of these newly emerged norms, especially when challenged by a more well-entrenched, traditional norm. [ABSTRACT FROM AUTHOR]

Aim: Coronavirus is an airborne and infectious disease and it is crucial to check the impact of climatic risk factors on the transmission of COVID-19. The main objective of this study is to determine the effect of climate risk factors using Bayesian regression analysis. Methods: Coronavirus disease 2019, due to the effect of the SARS-CoV-2 virus, has become a serious global public health issue. This disease was identified in Bangladesh on March 8, 2020, though it was initially identified in Wuhan, China. This disease is rapidly transmitted in Bangladesh due to the high population density and complex health policy setting. To meet our goal, The MCMC with Gibbs sampling is used to draw Bayesian inference, which is implemented in WinBUGS software. Results: The study revealed that high temperatures reduce confirmed cases and deaths from COVID-19, but low temperatures increase confirmed cases and deaths. High temperatures have decreased the proliferation of COVID-19, reducing the virus's survival and transmission. Conclusions: Considering only the existing scientific evidence, warm and wet climates seem to reduce the spread of COVID-19. However, more climate variables could account for explaining most of the variability in infectious disease transmission. [ABSTRACT FROM AUTHOR]

Myricetin, a natural flavonoid found in various foods, was investigated for its antiviral effect against transmissible gastroenteritis virus (TGEV). This a-coronavirus causes significant economic losses in the global swine industry. The study focused on the papain-like protease (PLpro), which plays a crucial role in coronavirus immune evasion by mediating deubiquitination. Targeting PLpro could potentially disrupt viral replication and enhance antiviral responses. The results demonstrated that myricetin effectively inhibited TGEV-induced cytopathic effects in a dose-dependent manner, with an EC50 value of 31.19 mM. Myricetin significantly reduced TGEV viral load within 48 h after an 8-h co-incubation period. Further investigations revealed that myricetin at a concentration of 100 mM directly inactivated TGEV and suppressed its intracellular replication stage. Moreover, pretreatment with 100 mM myricetin conferred a protective effect on PK-15 cells against TGEV infection. Myricetin competitively inhibited PLpro with an IC50 value of 6.563 mM. Molecular docking experiments show that myricetin binds to the Cys102 residue of PLpro through conventional hydrogen bonds, Pi-sulfur, and Pi-alkyl interactions. This binding was confirmed through site-directed mutagenesis experiments, indicating myricetin as a potential candidate for preventing and treating TGEV infection. [ABSTRACT FROM AUTHOR]

We generated a replication-competent OC43 human seasonal coronavirus (CoV) expressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike in place of the native spike (rOC43-CoV2 S). This virus is highly attenuated relative to OC43 and SARS-CoV-2 in cultured cells and animals and is classified as a biosafety level 2 (BSL-2) agent by the NIH biosafety committee. Neutralization of rOC43-CoV2 S and SARS-CoV-2 by S-specific monoclonal antibodies and human sera is highly correlated, unlike recombinant vesicular stomatitis virus-CoV2 S. Single-dose immunization with rOC43-CoV2 S generates high levels of neutralizing antibodies against SARS-CoV-2 and fully protects human ACE2 transgenic mice from SARS-CoV-2 lethal challenge, despite nondetectable replication in respiratory and nonrespiratory organs. rOC43-CoV2 S induces S-specific serum and airway mucosal immunoglobulin A and IgG responses in rhesus macaques. rOC43-CoV2 S has enormous value as a BSL-2 agent to measure S-specific antibodies in the context of a bona fide CoV and is a candidate live attenuated SARS-CoV-2 mucosal vaccine that preferentially replicates in the upper airway. [ABSTRACT FROM AUTHOR]

The relationship between pangolin-CoV and SARS-CoV-2 has been a subject of debate. Further evidence of a special relationship between the two viruses can be found by the fact that all known COVID-19 viruses have an abnormally hard outer shell (low M disorder, i.e., low content of intrinsically disordered residues in the membrane (M) protein) that so far has been found in CoVs associated with burrowing animals, such as rabbits and pangolins, in which transmission involves virus remaining in buried feces for a long time. While a hard outer shell is necessary for viral survival, a harder inner shell could also help. For this reason, the N disorder range of pangolin-CoVs, not bat-CoVs, more closely matches that of SARS-CoV-2, especially when Omicron is included. The low N disorder (i.e., low content of intrinsically disordered residues in the nucleocapsid (N) protein), first observed in pangolin-CoV-2017 and later in Omicron, is associated with attenuation according to the Shell-Disorder Model. Our experimental study revealed that pangolin-CoV-2017 and SARS-CoV-2 Omicron (XBB.1.16 subvariant) show similar attenuations with respect to viral growth and plaque formation. Subtle differences have been observed that are consistent with disorder-centric computational analysis. [ABSTRACT FROM AUTHOR]

Protein ADP-ribosylation plays important but ill-defined roles in antiviral signalling cascades such as the interferon response. Several viruses of clinical interest, including coronaviruses, express hydrolases that reverse ADP-ribosylation catalysed by host enzymes, suggesting an important role for this modification in host-pathogen interactions. However, which ADP-ribosyltransferases mediate host ADP-ribosylation, what proteins and pathways they target and how these modifications affect viral infection and pathogenesis is currently unclear. Here we show that host ADP-ribosyltransferase activity induced by IFNγ signalling depends on PARP14 catalytic activity and that the PARP9/DTX3L complex is required to uphold PARP14 protein levels via post-translational mechanisms. Both the PARP9/DTX3L complex and PARP14 localise to IFNγ-induced cytoplasmic inclusions containing ADP-ribosylated proteins, and both PARP14 itself and DTX3L are likely targets of PARP14 ADP-ribosylation. We provide evidence that these modifications are hydrolysed by the SARS-CoV-2 Nsp3 macrodomain, shedding light on the intricate cross-regulation between IFN-induced ADP-ribosyltransferases and the potential roles of the coronavirus macrodomain in counteracting their activity. Synopsis: Protein ADP-ribosylation plays important but ill-defined roles in antiviral signaling cascades. This study demonstrates that PARP9, DTX3L and PARP14 regulate IFNγ-induced ADP-ribosylation, and explores an intricate cross-regulation between these factors proposed to be targets of the coronavirus macrodomain. PARP14 catalytic activity is required for IFNγ-induced ADP-ribosylation. PARP9 and DTX3L regulate PARP14 protein stability. PARP9, DTX3L, PARP14 and ADPr co-localize in IFNγ-induced cytoplasmic structures. IFNγ induces PARP14-dependent modification of itself and of DTX3L, which may be hydrolyzed by the SARS-CoV2 macrodomain. Interferon signaling induces cytoplasmic colocalization and cross-regulation of two ADP-ribosyltransferases and a ubiquitin ligase. [ABSTRACT FROM AUTHOR]

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Introduction: Feline Infectious Peritonitis (FIP) has historically been a fatal coronavirus disease in cats. In recent years, the therapeutic agent GS-441524, developed by Gilead Sciences, was found to be a successful treatment for FIP in most patients in clinical trials. However, this particular drug has remained stalled in the therapeutic pipeline, leaving patients and cat owners without a licensed medication. In the meantime, online social media platforms began to emerge, connecting cat owners with a community of citizen non-veterinary professionals sourcing unlicensed GS-441524. Methods: This study prospectively followed participants (N  =  141) that successfully completed 12 weeks of treatment, capturing their treatment experiences with self-administered GS-441524-like medication. A one-time survey was administered to enrolled participants with mixed format of questions (open-ended and multiple-choice) asking about treatment administration techniques, observed side effects of GS-441524, accrued cost, veterinarian involvement, impact on the cat-human bond, and social media usage. Results: Our results show cat owners experienced a shift in treatment modality from injectable GS-441524 to pill formulation across the treatment period. The average total cost of medication has decreased since 2021 to approximately USD 3100, and participants reported the human–animal bond being affected negatively. Additionally, there was an increased trend in veterinarian awareness of GS-441524-like therapeutics and monitoring of clients undergoing treatment. Social media usage was reported as being important at the beginning of treatment to establish treatment administration but lessened by the end of treatment. Discussion: This study is the first detailed, prospective account of owner experiences with unlicensed GS-441524, raising an important discussion surrounding citizen veterinary medicine. [ABSTRACT FROM AUTHOR]

The study aimed to investigate molecularly the presence of flea-borne viruses in infested small ruminants with fleas. It was carried out in Egypt's Northern West Coast (NWC) and South Sinai Governorate (SSG). Three specific primers were used targeting genes, ORF103 (for Capripoxvirus and Lumpy skin disease virus), NS3 (for Bluetongue virus), and Rdrp (for Coronavirus), followed by gene sequencing and phylogenetic analyses. The results revealed that 78.94% of sheep and 65.63% of goats were infested in the NWC area, whereas 49.76% of sheep and 77.8% of goats were infested in the SSG region. Sheep were preferable hosts for flea infestations (58.9%) to goats (41.1%) in the two studied areas. Sex and age of the animals had no effects on the infestation rate (p > 0.05). The season and site of infestation on animals were significantly different between the two areas (p < 0.05). Ctenocephalides felis predominated in NWC and Ctenocephalides canis in SSG, and males of both flea species were more prevalent than females. Molecular analysis of flea DNA revealed the presence of Capripoxvirus in all tested samples, while other viral infections were absent. Gene sequencing identified three isolates as sheeppox viruses, and one as goatpox virus. The findings suggest that Capripoxvirus is adapted to fleas and may be transmitted to animals through infestation. This underscores the need for ongoing surveillance of other pathogens in different regions of Egypt. [ABSTRACT FROM AUTHOR]