- Acceptability and feasibility of a theatre-based wellness programme to support people living with Long COVID: a single arm feasibility study. -
Objectives: To determine acceptability and feasibility of a theatre-based wellness programme to support the health and wellbeing of people with long COVID. Design: Single group, repeated measures feasibility study. Setting: Community centre and online. Participants: Adults with a diagnosis of long COVID experiencing breathlessness, mild to moderate pain, and/or loneliness. Intervention: A six-week participatory creative intervention delivered to two groups of participants, one online and one in-person. The groups were facilitated by movement, voice and drama consultants and designed to improve wellbeing, fatigue, pain, strength and balance through a series of breathing exercises, visualisation, group singing and sound imagery, storytelling, movement exercises and poetry. Primary outcome measures: Acceptability of the intervention and feasibility of recruitment procedures and data collection. Secondary outcome measures: Changes in mental health, wellbeing, quality of life, loneliness, social support, fatigue, breathlessness, and post-COVID-19 functional status. Results: 20 participants took part in the intervention, 19 completed baseline assessments and 16 completed study follow-up. Most participants found the programme acceptable and feasible and improvements were identified in all outcomes at 8-week follow-up, including decreases in generalised anxiety and depressive symptoms, loneliness, shortness of breath, respiratory dysfunction, chronic fatigue and increased mental wellbeing, social support, and self-rated health. Key programme features and mechanisms of action that led to improvements in health and wellbeing were identified in qualitative interviews. Barriers to engagement included: activities being outside of the participant’s comfort zone, ongoing and fluctuating long COVID symptoms, emotional consequences of sharing experiences with the group and connectivity and connecting with others online. Conclusions: A six-week theatre-based programme was perceived as acceptable to most participants and resulted in positive psychosocial impacts. The findings provide a rationale for supporting the ongoing development of this and related programmes and for scaling up research into arts programmes to support people living with long COVID.
- Artificial Intelligence and Robotics for Reducing Waste in the Food Supply Chain: Systematic Literature Review, Theoretical Framework, and Research Agenda -
The COVID-19 pandemic has unraveled the inefficiencies in the global food supply chain. One glaring distortion is the wastage of close to a third of global food production, in the face of widespread food insecurity. With population explosion and climate change as additional pressure points, reducing food waste has emerged as an urgent imperative for achieving food security for all. In this paper, we develop a research framework and agenda for the use of Artificial Intelligence and robotics in reducing food loss and waste. The Cognitive Automation for Food (COGAF) has been developed as a theoretical framework for guiding future research. This framework delineates the research landscape into five distinct research streams: sensory enhancement, cognitive automation, physical automation, sensory-motor fusion, and collaborative automation. In order to develop a systematic research agenda, propositions have been developed in each of these research streams. In conjunction with the COGAF framework, this research agenda attempts to provide a road map for future research and knowledge creation pertaining to the use of AI and robotics to reduce food loss and waste.
- Ursodeoxycholic acid and severe COVID-19 outcomes in people with liver disease: a cohort study using the OpenSAFELY platform -
Biological evidence suggests ursodeoxycholic acid (UDCA) - a common treatment of cholestatic liver disease - may prevent severe COVID-19 outcomes. With the approval of NHS England, we conducted a population-based cohort study using primary care records, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. We estimated the hazard of COVID-19 hospitalisation or death between 1 March 2020 and 31 December 2022, comparing UDCA treatment to no UDCA treatment in a population with indication. Of 11,320 eligible individuals, 642 were hospitalised or died with COVID-19 during follow-up, 402 (63%) events among UDCA users. After confounder adjustment, UDCA was associated with a 21% (95% CI 7%-33%) relative reduction in the hazard of COVID-19 hospitalisation or death, consistent with an absolute risk reduction of 1.3% (95% CI 1.0%-1.6%). Our findings support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.
- A software tool for at-home measurement of sensorimotor adaptation -
Sensorimotor adaptation is traditionally studied in well-controlled laboratory settings with specialized equipment. However, recent public health concerns such as the COVID-19 pandemic, as well as a desire to recruit a more diverse study population, have led the motor control community to consider at-home study designs. At-home motor control experiments are still rare because of the requirement to write software that can be easily used by anyone on any platform. To this end, we developed software that runs locally on a personal computer. The software provides audiovisual instructions and measures the ability of the subject to control the cursor in the context of visuomotor perturbations. We tested the software on a group of at-home participants and asked whether the adaptation principles inferred from in-lab measurements were reproducible in the at-home setting. For example, we manipulated the perturbations to test whether there were changes in adaptation rates (savings and interference), whether adaptation was associated with multiple timescales of memory (spontaneous recovery), and whether we could selectively suppress subconscious learning (delayed feedback, perturbation variability) or explicit strategies (limited reaction time). We found remarkable similarity between in-lab and at-home behaviors across these experimental conditions. Thus, we developed a software tool that can be used by research teams with little or no programming experience to study mechanisms of adaptation in an at-home setting.
- Identification of an allele-specific transcription factor binding interaction that regulates PLA2G2A gene expression -
The secreted phospholipase A2 (sPLA2) isoform, sPLA2-IIA, has been implicated in a variety of diseases and conditions, including bacteremia, cardiovascular disease, COVID-19, sepsis, adult respiratory distress syndrome, and certain cancers. Given its significant role in these conditions, understanding the regulatory mechanisms impacting its levels is crucial. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs), including rs11573156, that are associated with circulating levels of sPLA2-IIA. Through Genotype-Tissue Expression (GTEx), 234 expression quantitative trait loci (eQTLs) were identified for the gene that encodes for sPLA2-IIA, PLA2G2A. SNP2TFBS (https://ccg.epfl.ch/snp2tfbs/) was utilized to ascertain the binding affinities between transcription factors (TFs) to both the reference and alternative alleles of identified SNPs. Subsequently, ChIP-seq peaks highlighted the TF combinations that specifically bind to the SNP, rs11573156. SP1 emerged as a significant TF/SNP pair in liver cells, with rs11573156/SP1 interaction being most prominent in liver, prostate, ovary, and adipose tissues. Further analysis revealed that the upregulation of PLA2G2A transcript levels through the rs11573156 variant was affected by tissue SP1 protein levels. By leveraging an ordinary differential equation, structured upon Michaelis-Menten enzyme kinetics assumptions, we modeled the PLA2G2A transcription's dependence on SP1 protein levels, incorporating the SNP's influence. Collectively, these data strongly suggest that the binding affinity differences of SP1 for the different rs11573156 alleles can influence PLA2G2A expression. This, in turn, can modulate sPLA2-IIA levels, impacting a wide range of human diseases.
- Leveraging Tuberculosis Programs for Future Pandemic Preparedness: A Retrospective Look on COVID-19 -
Worldwide, COVID-19 has decimated healthcare systems and highlighted the pressing need to ensure resilience for future pandemics. Given the almost 30% likelihood of another respiratory disease similar to COVID-19 manifesting in the next 10 years, it is imperative to prioritize pandemic preparedness in the immediate future. To this end, tuberculosis (TB) and its management share many similarities to respiratory disease protection, offering an opportunity to dually strengthen TB programs and protect against future pandemics. Looking at data from the World Health Organization (WHO), Global Fund, Our World in Data, and domestic health ministries. It was hypothesized that countries that had better TB program strength going into the pandemic fared better with COVID-19 than those with poorer TB treatment. It was found that countries that recovered their TB program strength (as measured by TB treatment coverage percentages) to or above pre-pandemic levels fared better in terms of COVID-19 pandemic incidence and death. Case studies helped identify common factors across resilient TB platforms in dually successful COVID-19 and TB countries, including community trust, co-epidemic responses that were able to maintain continuity of care, sustained innovation, comprehensive communication across public and private sectors, and maintenance of donor support for TB programs through the pandemic.
- EduMap: Navigating a Learning Adventure -
Directed study maps are often used in order to create an overlay of knowledge relations. However, these connections often have to manually be created by subject matter and IT experts, which, although are a ground truth, limit these user to the topics of the maps at hand. To address this, we propose EduMap, which takes advantage of GPT 3.5 in a few-shot setting to create a study map for any user-provided topic. We conducted two user studies to address various aspects of the map: (1) A quantitative study to test out the effectiveness of this map medium in the context of navigating information concerning COVID-19 in a expert-curated graph, and (2) A quantitative study to test out the accuracy and usefulness of GPT-generated graphs. Our results show that the map medium is effective, and, though the graphs produced make sense, there is work to be done before it can be considered ground truth, with issues of vague topics and improper connections between topics arising. Altogether, our results establish a baseline for AI-generated study maps to be improved upon in the future with ground truth to create a more trustworthy software.
- Self-inhibiting percolation and viral spreading in epithelial tissue -
SARS-CoV-2 induces delayed type-I/III interferon production, allowing it to escape the early innate immune response. The delay has been attributed to a deficiency in the ability of cells to sense viral replication upon infection, which in turn hampers activation of the antiviral state in bystander cells. Here, we introduce a cellular automaton model to investigate the spatiotemporal spreading of viral infection as a function of virus and host-dependent parameters. The model suggests that the considerable person-to-person heterogeneity in SARS-CoV-2 infections is a consequence of high sensitivity to slight variations in biological parameters near a critical threshold. It further suggests that within-host viral proliferation can be curtailed by the presence of remarkably few cells that are primed for IFN production. Thus, the observed heterogeneity in defense readiness of cells reflects a remarkably cost-efficient strategy for protection.
- Syncytia Formation Promotes Virus Resistance to Interferon and Neutralizing Antibodies -
SARS-CoV-2, like many viruses, generates syncytia. Using SARS-CoV-2 and S (S) expressing recombinant vesicular stomatitis and influenza A viruses, we show that S-mediated syncytia formation provides resistance to interferons in cultured cells, human small airway-derived air-liquid interface cultures and hACE2 transgenic mice. Amino acid substitutions that modulate fusogenicity in Delta- and Omicron-derived S have parallel effects on viral interferon resistance. Syncytia formation also decreases antibody virus neutralization activity in cultured cells. These findings explain the continued selection of fusogenic variants during SARS-CoV-2 evolution in humans and, more generally, the evolution of fusogenic viruses despite the adverse effects of syncytia formation on viral replication in the absence of innate or adaptive immune pressure.
- A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines -
Continuous evolution of SARS-CoV-2 alters the antigenicity of the immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining the efficacy of vaccines and monoclonal antibody therapies. To overcome this challenge, we set out to develop a vaccine focusing antibody responses on the highly conserved but metastable S2 subunit, which folds as a spring-loaded fusion machinery. Here, we describe a protein design strategy enabling prefusion-stabilization of the SARS-CoV-2 S2 subunit and high yield recombinant expression of trimers with native structure and antigenicity. We demonstrate that our design strategy is broadly generalizable to all sarbecoviruses, as exemplified with the SARS-CoV-1 (clade 1a) and PRD-0038 (clade 3) S2 fusion machineries. Immunization of mice with a prefusion-stabilized SARS-CoV-2 S2 trimer vaccine elicits broadly reactive sarbecovirus antibody responses and neutralizing antibody titers of comparable magnitude against Wuhan-Hu-1 and the immune evasive XBB.1.5 variant. Vaccinated mice were protected from weight loss and disease upon challenge with SARS-CoV-2 XBB.1.5, providing proof-of-principle for fusion machinery sarbecovirus vaccines motivating future development.
- SARS-CoV-2 induces acute neurological signs while Calcitonin Gene-Related Peptide (CGRP) signaling blockade reduces interleukin 6 (IL-6) release and weight loss in mouse models -
COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. We evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 CGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. We determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking CGRP. These findings suggest that blockage of CGRP signaling protects against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection.
- SARS-CoV-2 nsp15 preferentially degrades AU-rich dsRNA via its dsRNA nickase activity -
It has been proposed that coronavirus nsp15 mediates evasion of host cell double-stranded (ds) RNA sensors via its uracil-specific endoribonuclease activity. However, how nsp15 processes viral dsRNA, commonly considered as a genome replication intermediate, remains elusive. Previous research has mainly focused on short single-stranded RNA as substrates, and whether nsp15 prefers single-stranded or double-stranded RNA for cleavage is controversial. In the present work, we prepared numerous RNA substrates, including both long substrates mimicking the viral genome and short defined RNA, to clarify the substrate preference and cleavage pattern of SARS-CoV-2 nsp15. We demonstrated that SARS-CoV-2 nsp15 preferentially cleaved flexible pyrimidine nucleotides located in AU-rich areas and mismatch-containing areas in dsRNA via a nicking manner. The AU content and distribution in dsRNA along with the RNA length affected cleavage by SARS-CoV-2 nsp15. Because coronavirus genomes generally have a high AU content, our work supported the mechanism that coronaviruses evade the antiviral response mediated by host cell dsRNA sensors by using nsp15 dsRNA nickase to directly cleave dsRNA intermediates formed during genome replication and transcription.
- G6PD deficiency mediated impairment of iNOS and lysosomal acidification affecting phagocytotic clearance in microglia in response to SARS-CoV-2 -
The glucose-6-phosphate dehydrogenase (G6PD) deficiency is X-linked and is the most common enzymatic deficiency disorder globally. It is a crucial enzyme for the pentose phosphate pathway and produces NADPH, which plays a vital role in the regulation of oxidative stress of many cell types. The deficiency of G6PD causes hemolytic anemia, diabetes, cardiovascular and neurological disorders. Notably, the patient with G6PD deficiency was severely affected by SARS-CoV-2 and showed prolonged COVID-19 symptoms, neurological impacts, and high mortality. However, the mechanism of COVID-19 severity in G6PD deficient patients is still ambiguous. Here, using a CRISPR-edited G6PD deficient human microglia cell culture model, we observed a significant reduction in NADPH and an increase in basal reactive oxygen species (ROS) in microglia. Interestingly, the deficiency of the G6PD-NAPDH axis impairs induced nitric oxide synthase (iNOS) mediated nitric oxide (NO) production which plays a fundamental role in inhibiting viral replication. Surprisingly, we also observed that the deficiency of the G6PD-NADPH axis reduced lysosomal acidification, which further abrogates the lysosomal clearance of viral particles. Thus, impairment of NO production and lysosomal acidification as well as redox dysregulation in G6PD deficient microglia altered innate immune response, promoting the severity of SARS-CoV-2 pathogenesis.
- The complement pattern recognition molecule CL-11 promotes invasion and injury of respiratory epithelial cells by SARS-CoV-2. -
Collectin-11 is a soluble C-type lectin produced at epithelial surfaces to initiate pathogen elimination by complement. Given the respiratory epithelium is a source of CL-11 and downstream complement-pathway components, we investigated the potential of CL-11 to impact the pathogenicity of SARS-CoV-2. While the SARS-CoV-2 spike trimer could bind CL-11 and trigger complement activation followed by MAC formation, the virus was resistant to lysis. Surprisingly, virus production by infected respiratory epithelial cells was enhanced by CL-11 opsonisation of virus but this effect was fully inhibited by sugar-blockade of CL-11. Moreover, SARS-CoV-2 spike protein expressed at the bronchial epithelial cell surface was associated with increased CL-11 binding and MAC formation. We propose that SARS-CoV-2 pathogenicity is exacerbated both by resistance to complement and CL-11 driven respiratory cell invasion and injury at the portal of entry. Contrary to expectation, CL-11 blockade could offer a novel approach to limit the pathogenicity of SARS-CoV-2.
- Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures -
Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a ‘preeclampsia-like syndrome’. However, the mechanisms underpinning SARS-CoV-2-induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS-CoV-2 infection. Methods: We utilized whole-transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS-CoV-2 in the third trimester of their pregnancy (n=7) and those collected prior to the start of the coronavirus disease 2019 (COVID-19) pandemic (n=9). Results: Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified signatures associated with hypoxia and placental dysfunction during SARS-CoV-2 infection in pregnancy. Notably, genes associated with vasodilation (NOS3), oxidative stress (GDF15, CRH), and preeclampsia (FLT1, EGFR, KISS1, PAPPA2), were enriched with SARS-CoV-2. Pathways related to increased nutrient uptake, vascular tension, hypertension, and inflammation, were also enriched in SARS-CoV-2 samples compared to uninfected controls. Conclusions: Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS-CoV-2 infection.
EXERCISE TRAINING USING AN APP ON PHYSICAL CARDIOVASCULAR FUNCTION INDIVIDUALS WITH POST-COVID-19 SYNDROME - Conditions: Post-Acute COVID-19 Syndrome
Interventions: Behavioral: Exercise; Behavioral: Control
Sponsors: University of Nove de Julho
Not yet recruiting
A Phase 1 Trial of Recombinant COVID-19 Trivalent Protein Vaccine （CHO Cell）LYB002V14 in Booster Vaccination - Conditions: SARS-CoV-2; COVID-19 Vaccine
Interventions: Biological: 30μg dose of LYB002V14; Biological: 60μg dose of LYB002V14; Biological: placebo
Sponsors: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.
Not yet recruiting
COVID-19 Vaccine Effectiveness Against Recurrent Infection Among Lung Cancer Patients and Biomarker Research - Conditions: COVID-19 Recurrent; Lung Cancer; Vaccination; Antibody; Chemotherapy; Immune Checkpoint Inhibitor
Interventions: Biological: Any Chinese government-recommended COVID-19 booster vaccine
Sponsors: Peking Union Medical College Hospital
Recruiting
IMMUNERECOV CONTRIBUTES TO IMPROVEMENT OF RESPIRATORY AND IMMUNOLOGICAL RESPONSE IN POST-COVID-19 PATIENTS. - Conditions: Long Covid19; Dietary Supplements; Respiratory Tract Infections; Inflammation
Interventions: Dietary Supplement: Nutritional blend (ImmuneRecov).
Sponsors: Federal University of São Paulo
Recruiting
Study on Post-Acute COVID-19 Syndrome in Improvement of COVID-19 Rehabilitated Patients by Respiratory Training - Conditions: COVID-19, Post-Acute COVID-19 Syndrome, Dyspnea, Incentive Spirometer
Interventions: Device: breathing training
Sponsors: Tri-Service General Hospital
Active, not recruiting
Physical Activity Coaching in Patients With Post-COVID-19 - Conditions: Post-COVID-19 Syndrome
Interventions: Behavioral: Self-monitoring; Behavioral: Goal setting and review; Behavioral: Education; Behavioral: Feedback; Behavioral: Contact; Behavioral: Exercise; Behavioral: Report; Behavioral: Social support; Behavioral: Group activities; Behavioral: World Health Organization recommendations for being physically active
Sponsors: University of Alcala; Professional College of Physiotherapists of the Community of Madrid
Not yet recruiting
Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID - Conditions: Long COVID; Post Acute Sequelae of COVID-19; Post-Acute COVID-19
Interventions: Drug: Ensitrelvir; Other: Placebo
Sponsors: Timothy Henrich; Shionogi Inc.
Not yet recruiting
Low-intensity Aerobic Training Associated With Global Muscle Strengthening in Post-COVID-19 - Conditions: COVID-19
Interventions: Procedure: muscle strengthening
Sponsors: Centro Universitário Augusto Motta
Completed
Intravenous Immunoglobulin Replacement Therapy for Persistent COVID-19 in Patients With B-cell Impairment - Conditions: COVID-19
Interventions: Drug: Immunoglobulins
Sponsors: Jaehoon Ko
Not yet recruiting
Effect of Inhaled Hydroxy Gas on Long COVID Symptoms - Conditions: Post-Acute COVID-19 Syndrome
Interventions: Device: Hydroxy gas
Sponsors: Oxford Brookes University
Recruiting
PROmotion of COVID-19 BOOSTer VA(X)Ccination in the Emergency Department - PROBOOSTVAXED - Conditions: COVID-19
Interventions: Behavioral: Vaccine Messaging; Behavioral: Vaccine Acceptance Question
Sponsors: University of California, San Francisco; National Institute of Allergy and Infectious Diseases (NIAID); Pfizer; Duke University; Baylor College of Medicine; Thomas Jefferson University
Not yet recruiting
Community Care Intervention to Decrease COVID-19 Vaccination Inequities - Conditions: COVID-19 Vaccination
Interventions: Behavioral: Community Health Worker Intervention to Enhance Vaccination Behavior (CHW-VB)
Sponsors: RAND; Clinical Directors Network; National Institute on Minority Health and Health Disparities (NIMHD)
Recruiting
Stem Cell Study for Long COVID-19 Neurological Symptoms - Conditions: Post-Acute COVID-19 Syndrome
Interventions: Biological: Stem Cell
Sponsors: Charles Cox; CBR Systems, Inc.
Not yet recruiting
Multilevel Intervention of COVID-19 Vaccine Uptake Among Latinos - Conditions: Vaccine Hesitancy
Interventions: Behavioral: Multilevel Intervention
Sponsors: San Diego State University
Not yet recruiting
Pursuing Reduction in Fatigue After COVID-19 Via Exercise and Rehabilitation (PREFACER): A Randomized Feasibility Trial - Conditions: Long-COVID; Long Covid19; Post-COVID-19 Syndrome; Post-COVID Syndrome; Fatigue
Interventions: Other: COVIDEx
Sponsors: Lawson Health Research Institute; Western University
Not yet recruiting
Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research - As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID-19) today, arbidol often involves drug-drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to detect arbidol and its metabolite arbidol sulfoxide (M6-1) levels in vivo and in vitro. In this study, a 200 μL incubation system was used to study the inhibitory…
Tumor Treating Fields (TTFields) demonstrate antiviral functions in vitro, and safety for application to COVID-19 patients in a pilot clinical study - Coronaviruses are the causative agents of several recent outbreaks, including the COVID-19 pandemic. One therapeutic approach is blocking viral binding to the host receptor. As binding largely depends on electrostatic interactions, we hypothesized possible inhibition of viral infection through application of electric fields, and tested the effectiveness of Tumor Treating Fields (TTFields), a clinically approved cancer treatment based on delivery of electric fields. In preclinical models,…
Repurposing of Rutan showed effective treatment for COVID-19 disease - Previously, from the tannic sumac plant (Rhus coriaria), we developed the Rutan 25 mg oral drug tablets with antiviral activity against influenza A and B viruses, adenoviruses, paramyxoviruses, herpes virus, and cytomegalovirus. Here, our re-purposing study demonstrated that Rutan at 25, 50, and 100 mg/kg provided a very effective and safe treatment for COVID-19 infection, simultaneously inhibiting two vital enzyme systems of the SARS-CoV-2 virus: 3C-like proteinase (3CLpro) and RNA-dependent…
Inhibition of the KCa2 potassium channel in atrial fibrillation: a randomized phase 2 trial - Existing antiarrhythmic drugs to treat atrial fibrillation (AF) have incomplete efficacy, contraindications and adverse effects, including proarrhythmia. AP30663, an inhibitor of the K(Ca)2 channel, has demonstrated AF efficacy in animals; however, its efficacy in humans with AF is unknown. Here we conducted a phase 2 trial in which patients with a current episode of AF lasting for 7 days or less were randomized to receive an intravenous infusion of 3 or 5 mg kg^(-1) AP30663 or placebo. The…
Angiotensin Converting Enzyme 2 Does Not Facilitate Porcine Epidemic Diarrhea Virus Entry into Porcine Intestinal Epithelial Cells and Inhibits It-induced Inflammatory Injury by Promoting STAT1 Phosphorylation - ACE2 has been confirmed to be a functional receptor for SARS-CoV and SARS-CoV-2, but research on animal coronaviruses, especially PEDV, are still unknown. The present study investigated whether ACE2 plays a role in receptor recognition and subsequent infection during PEDV invasion of host cells. IPEC-J2 cells stably expressing porcine ACE2 did not increase the production of PEDV-N but inhibited its expression. Porcine ACE2 knockout cells was generated by CRISPR/Cas9 genome editing in IPEC-J2…
The environmental impact of mask-derived microplastics on soil ecosystems - During the COVID-19 pandemic, a significant increased number of masks were used and improperly disposed of. For example, the global monthly consumption of approximately 129 billion masks. Masks, composed of fibrous materials, can readily release microplastics, which may threaten various soil ecosystem components such as plants, animals, microbes, and soil properties. However, the specific effects of mask-derived microplastics on these components remain largely unexplored. Here, we investigated…
Hospital healthcare workers’ use of facial protective equipment before the COVID-19 pandemic, implications for future policy - CONCLUSION: This study identified key determinants of FPE behavior. A review of context specific FPE guidance for ED by infection prevention and control professionals would help to promote practicable, sustainable compliance.
Hybrid immunity from SARS-CoV-2 infection and mRNA BNT162b2 vaccine among Thai school-aged children - CONCLUSIONS: Immune response that arises from BNT162b2 vaccine after natural infection and infection after 2 doses of BNT162b2 was higher than infection after partially-vaccinated children.
Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2 - CONCLUSION: The IC(50) for all the drugs, except ivermectin, was at the clinically achievable plasma concentration in humans, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.
Evaluation of the clinical efficacy of racecadotril in the treatment of neonatal calves with infectious diarrhea - Racecadotril, used as an antidiarrheal drug in humans and some animals such as the dog, inhibits peripheral enkephalinase, which degrades enkephalins and enkephalinase inhibition induces a selective increase in chloride absorption from the intestines. The study material consisted of 46 calves with infectious diarrhea and 14 healthy calves in the age 2-20 days. The calves were divided into eight groups; healthy calves (HG), healthy calves administered racecadotril (HRG), calves with…
An ncRNA transcriptomics-based approach to design siRNA molecules against SARS-CoV-2 double membrane vesicle formation and accessory genes - CONCLUSION: Our novel in silico pipeline integrates effective methods from previous studies to predict and validate siRNA molecules, having the potential to inhibit viral replication pathway in vitro. In total, this study identified 17 highly specific siRNA molecules targeting NSP3, 4, and 6 and accessory genes ORF3a, 7a, 8, and 10 of SARS-CoV-2, which might be used as an additional antiviral treatment option especially in the cases of life-threatening urgencies.
Elevated peripheral levels of receptor-interacting protein kinase 1 (RIPK1) and IL-8 as biomarkers of human amyotrophic lateral sclerosis - Amyotrophic lateral sclerosis (ALS) is a devastating fatal neurodegenerative disease with no cure. Receptor-interacting protein kinase 1 (RIPK1) has been proposed to mediate pathogenesis of ALS. Primidone has been identified as an old drug that can also inhibit RIPK1 kinase. We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1^(G93A) mice and ALS patients. SOD1^(G93A) mice treated with primidone showed significant delay of symptomatic onset and improved…
Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies - We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active…
Enhancement efficiency delivery of antiviral Molnupiravir-drug via the loading with self-assembly nanoparticles of pycnogenol and cellulose which are decorated by zinc oxide nanoparticles for COVID-19 therapy - The target of the study is to modify the efficiency of Molnupiravir-drug (MOL) for COVID-19 therapy via the rearrangement of the building engineering of MOL-drug by loading it with self-assembly biomolecules nanoparticles (NPs) of pycnogenol (Pyc) and cellulose (CNC) which are decorated by zinc oxide nanoparticles. The synthesis and characterization of the modified drug are performing successfully, the loading and release process of the MOL drug on a nano surface is measured by UV-Vis…
Combating DC-SIGN-mediated SARS-CoV-2 dissemination by glycan-mimicking polymers - Many viruses exploit the human C-type lectin receptor dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) for cell entry and virus dissemination. An inhibition of DC-SIGN-mediated virus attachment by glycan-derived ligands has, thus, emerged as a promising strategy toward broad-spectrum antiviral therapeutics. In this contribution, several cognate fragments of oligomannose- and complex-type glycans grafted onto a poly-l-lysine scaffold are evaluated as polyvalent DC-SIGN ligands. The…