Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• Pre-existing interferon gamma conditions the lung to mediate early control of SARS-CoV-2 -
  Interferons (IFNs) are critical for anti-viral host defence. Type-1 and type-3 IFNs are typically associated with early control of viral replication and promotion of inflammatory immune responses; however, less is known about the role of IFN{gamma} in anti-viral immunity, particularly in the context of SARS-CoV-2. We have previously observed that lung infection with attenuated bacteria Mycobacterium bovis BCG achieved though intravenous (iv) administration provides strong protection against SARS-CoV-2 (SCV2) infection and disease in two mouse models. Assessment of the pulmonary cytokine milieu revealed that iv BCG induces a robust IFN{gamma} response and low levels of IFN{beta}. Here we examined the role of ongoing IFN{gamma} responses due to pre-established bacterial infection on SCV2 disease outcomes in two murine models. We report that IFN{gamma} is required for iv BCG induced reduction in pulmonary viral loads and that this outcome is dependent on IFN{gamma} receptor expression by non-hematopoietic cells. Further analysis revealed that BCG infection promotes the upregulation of interferon-stimulated genes (ISGs) with reported anti-viral activity by pneumocytes and bronchial epithelial cells in an IFN{gamma}-dependent manner, suggesting a possible mechanism for the observed protection. Finally, we confirmed the importance of IFN{gamma} in these anti-viral effects by demonstrating that the recombinant cytokine itself provides strong protection against SCV2 challenge when administered intranasally. Together, our data show that a pre-established IFN{gamma} response within the lung is protective against SCV2 infection, suggesting that concurrent or recent infections that drive IFN{gamma} may limit the pathogenesis of SCV2 and supporting possible prophylactic uses of IFN{gamma} in COVID-19 management.
  🖺 Full Text HTML: Pre-existing interferon gamma conditions the lung to mediate early control of SARS-CoV-2
• Using big sequencing data to identify chronic SARS-Coronavirus-2 infections -
  The evolution of SARS-Coronavirus-2 (SARS-CoV-2) has been characterized by the periodic emergence of highly divergent variants, many of which may have arisen during chronic infections of immunocompromised individuals. Here, we harness a global phylogeny of ~11.7 million SARS-CoV-2 genomes and search for clades composed of sequences with identical metadata (location, age, and sex) spanning more than 21 days. We postulate that such clades represent repeated sampling from the same chronically infected individual. A set of 271 such chronic-like clades was inferred, and displayed signatures of an elevated rate of adaptive evolution, in line with validated chronic infections. More than 70% of adaptive mutations present in currently circulating variants are found in BA.1 chronic-like clades that predate the circulating variants by months, demonstrating the predictive nature of such clades. We find that in chronic-like clades the probability of observing adaptive mutations is approximately 10-20 higher than that in global transmission chains. We next employ language models to find mutations most predictive of chronic infections and use them to infer hundreds of additional chronic-like clades in the absence of metadata and phylogenetic information. Our proposed approach presents an innovative method for mining extensive sequencing data and providing valuable insights into future evolutionary patterns.
  🖺 Full Text HTML: Using big sequencing data to identify chronic SARS-Coronavirus-2 infections
• SIRT-1 is required for release of enveloped picornaviruses -
  Enterovirus D68 is a re-emerging enterovirus that causes acute respiratory illness in infants and has recently been linked to Acute Flaccid Myelitis. Here, we show that the histone deacetylase, SIRT-1, is essential for autophagy and EV-D68 infection. Knockdown of SIRT-1 inhibits autophagy and reduces EV-D68 extracellular titers. The proviral activity of SIRT-1 does not require its deacetylase activity or functional autophagy. SIRT-1’s proviral activity is, we demonstrate, mediated through the repression of ER stress. Inducing ER stress through thapsigargin treatment or SERCA2A knockdown in SIRT-1 knockdown cells had no additional effect on EV-D68 extracellular titers. Knockdown of SIRT-1 also decreases poliovirus and SARS-CoV-2 titers but not coxsackievirus B3. In non-lytic conditions, EV-D68 is primarily released in an enveloped form, and SIRT-1 is required for this process. Our data show that SIRT-1, through its translocation to the cytosol, is critical to promote the release of enveloped EV-D68 viral particles.
  🖺 Full Text HTML: SIRT-1 is required for release of enveloped picornaviruses
• Megakaryocyte infection by SARS-CoV-2 drives the formation of pathogenic afucosylated IgG antibodies in mice -
  Despite more than 90% of total plasma fucosylated IgG, specific IgGs with low core fucosylation are found sporadically in response to enveloped virus infections and to alloantigens on blood cells. IgG responses with low core fucosylation are directly pathogenic in SARS-CoV-2 and dengue infections. In COVID-19, formation of IgG with low core fucosylation (afucosylated IgG) against spike protein (S) predicts and directly mediates disease progression to severe form. Low fucosylation of IgG causes increased antibody-dependent cellular toxicity mediated by intense Fc{gamma}R-mediated stimulation of platelets, monocytes, macrophages, and natural killer cells. The mechanism of afucosylated IgG formation has remained elusive thus far in COVID-19, dengue infection, and other disorders. This study demonstrates that infection of megakaryocytes by SARS-CoV-2 drives the formation of pathogenic anti-S afucosylated IgGs, causing pulmonary vascular thrombosis, acute lung injury, and death in Fc{gamma}-expressing mice.
  🖺 Full Text HTML: Megakaryocyte infection by SARS-CoV-2 drives the formation of pathogenic afucosylated IgG antibodies in mice
• The lasting effects of the pandemic: A time series analysis of first-time speech delays in kids under 5 years of age -

  Given the profound effects of the COVID-19 pandemic on the way individuals interact, we sought to understand if there was an increase in pediatric first-time speech and language delay diagnoses in. We identified children under five years of age with a first-time speech delay diagnosis between January 1, 2018 and February 28, 2023, in Truveta Data. We calculated the monthly rate of first-time speech delay diagnoses per children with an encounter within the last year and no previous speech delay diagnosis. The Seasonal-Trend decomposition using LOESS (STL) method was used to adjust for seasonality. We also compared the difference in means between the 2018/2019 and 2021/2022 time periods. Significant increases in the mean of rates between 2018/2019 and 2021/2022 exist for the overall population and each age strata (p<0.001). Likely the causes of these trends are multifaceted and future research is needed to understand the specific drivers at play.

  🖺 Full Text HTML: The lasting effects of the pandemic: A time series analysis of first-time speech delays in kids under 5 years of age
• Remote self-report and speech-in-noise measures predict clinical audiometric thresholds -

  Developments in smartphone technology and the COVID-19 pandemic have highlighted the feasibility and need for remote, but reliable hearing tests. Previous studies used remote testing but did not directly compare results in the same listeners with standard lab or clinic testing. This study investigated reliability of remote, self-administered digits-in-noise (remote-DIN) compared with lab-based, supervised (lab-DIN) testing. Predictive validity was further examined in relation to a commonly used self-report, Speech, Spatial, and Qualities of Hearing (SSQ-12), and lab-based, pure tone audiometry. DIN speech reception thresholds (SRTs) of adults (18-64 y/o) with normal-hearing (NH, N=16) and hearing loss (HL, N=18), were measured using English-language digits (0-9), binaurally presented as triplets in one of four speech-shaped noise maskers (broadband, low-pass filtered at 2, 4, 8 kHz) and two digit phases (diotic, antiphasic). High, significant intraclass correlation coefficients indicated strong internal consistency of remote-DIN SRTs, which also correlated significantly with lab-DIN SRTs. There was no significant mean difference between remote- and lab-DIN on any tests. NH listeners had significantly higher SSQ scores, and remote- and lab-DIN SRTs than listeners with HL. All versions of remote-DIN SRTs correlated significantly with pure-tone-average (PTA), with the 2-kHz filtered test the best predictor, explaining 50% of variance in PTA. SSQ total score also significantly and independently predicted PTA (17% of variance) and all test versions of the remote-DIN, except the antiphasic BB test. This study shows that remote SSQ-12 and remote-DIN are sensitive tools for capturing important aspects of auditory function.

  🖺 Full Text HTML: Remote self-report and speech-in-noise measures predict clinical audiometric thresholds
• Comparative Analysis of Decision Trees on Two COVID-19 Symptom Datasets -

  Objective: This study compares decision trees on two COVID-19 symptom datasets to assess their performance and feature importance in predicting and understanding infection patterns. Methods: We created decision trees on Israeli and Swedish COVID-19 infection datasets. Performance metrics were used to assess their predictive capabilities, and feature importance analysis identified significant variables in the decision-making process. Results: The study observed different performance levels of decision trees on the COVID-19 datasets. The Swedish dataset achieved high accuracy and F1-score without hyperparameter tuning, while the Israeli dataset improved significantly with Extreme Gradient Boosting. Dataset characteristics impact the selection of an optimal decision tree algorithm. The key variable in both datasets was sore throat. Conclusion: This study compares decision trees on COVID-19 infection datasets, emphasizing the importance of dataset characteristics in selecting an optimal algorithm. Identifying significant features enhances understanding of infection patterns, benefiting decision-making and prediction accuracy in infectious disease analysis.

  🖺 Full Text HTML: Comparative Analysis of Decision Trees on Two COVID-19 Symptom Datasets
• Causal association of COVID-19 with brain structure changes: Findings from a non-overlapping 2-sample Mendelian randomization study -

  Recent cohort studies suggested that SARS-CoV-2 infection is associated with changes in brain structure. However, the potential causal relationship remains unclear. We performed a two-sample Mendelian randomization analysis to determine whether genetic susceptibility of COVID-19 is causally associated with changes in cortical and subcortical areas of the brain. This 2-sample MR (Mendelian Randomization) study is an instrumental variable analysis of data from the COVID-19 Host Genetics Initiative (HGI) meta-analyses round 5 excluding UK Biobank participants (COVID-19 infection, N=1,348,701; COVID-19 severity, N=1,557,411), the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) Global and regional cortical measures, N=33,709; combined hemispheric subcortical volumes, N=38,851), and UK Biobank (left/right subcortical volumes, N=19,629). A replication analysis was performed on summary statistics from different COVID-19 GWAS study (COVID-19 infection, N=80,932; COVID-19 severity, N=72,733). We found that the genetic susceptibility of COVID-19 was not significantly associated with changes in brain structures, including cortical and subcortical brain structure. Similar results were observed for different (1) MR estimates, (2) COVID-19 GWAS summary statistics, and (3) definitions of COVID-19 infection and severity. This study suggests that the genetic susceptibility of COVID-19 is not causally associated with changes in cortical and subcortical brain structure.

  🖺 Full Text HTML: Causal association of COVID-19 with brain structure changes: Findings from a non-overlapping 2-sample Mendelian randomization study
• Deep spatial proteomic exploration of severe COVID-19-related pulmonary injury in post-mortem specimens -
  The lung, as a primary target of SARS-CoV-2, exhibits heterogeneous microenvironment accompanied by various histopathological changes following virus infection. However, comprehensive insight into the protein basis of COVID-19-related pulmonary injury with spatial resolution is currently deficient. Here, we generated a region-resolved quantitative proteomic atlas of seven major pathological structures within the lungs of COVID-19 victims by integrating histological examination, laser microdissection, and ultrasensitive proteomic technologies. Over 10,000 proteins were quantified across 71 dissected FFPE post-mortem specimens. By comparison with control samples, we identified a spectrum of COVID-19-induced protein and pathway dysregulations in alveolar epithelium, bronchial epithelium, and pulmonary blood vessels, providing evidence for the proliferation of transitional-state pneumocytes. Additionally, we profiled the region-specific proteomes of hallmark COVID-19 pulmonary injuries, including bronchiole mucus plug, pulmonary fibrosis, airspace inflammation, and hyperplastic alveolar type 2 cells. Bioinformatic analysis revealed the enrichment of cell-type and functional markers in these regions (e.g. enriched TGFBI in fibrotic region). Furthermore, we identified the up-regulation of proteins associated with viral entry, host restriction, and inflammatory response in COVID-19 lungs, such as FURIN and HGF. Collectively, this study provides spatial proteomic insights for understanding COVID-19-caused pulmonary injury, and may serve as a valuable reference for improving therapeutic intervention for severe pneumonia.
  🖺 Full Text HTML: Deep spatial proteomic exploration of severe COVID-19-related pulmonary injury in post-mortem specimens
• National identity predicts public health support during a global pandemic -
  Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors that associated with people reported adopting public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.
  🖺 Full Text HTML: National identity predicts public health support during a global pandemic
• Partisan differences in physical distancing are linked to health outcomes during the COVID-19 pandemic. -
  Numerous polls suggest that COVID-19 is a profoundly partisan issue in the U.S. Using the geotracking data of 15 million smartphones per day, we found that U.S. counties that voted for Donald Trump (Republican) over Hillary Clinton (Democrat) in the 2016 presidential election exhibited 14% less physical distancing between March and May 2020. Partisanship was more strongly associated with physical distancing than numerous factors, including counties’ median income, COVID-19 cases, population density, and racial and age demographics. Contrary to our predictions, the observed partisan gap strengthened over time and remained when stay-at-home orders were active. Additionally, county-level consumption of conservative media (Fox News) related to reduced physical distancing. Finally, the observed partisan differences in distancing were associated with subsequently higher COVID-19 infection and fatality growth rates in pro-Trump counties. Taken together, these data suggest that U.S. citizens’ responses to COVID-19 are subject to a deep—and consequential—partisan divide.
  🖺 Full Text HTML: Partisan differences in physical distancing are linked to health outcomes during the COVID-19 pandemic.
• Using social and behavioural science to support COVID-19 pandemic response -
  The COVID-19 pandemic represents a massive global health crisis. Because the crisis requires large-scale behaviour change and places significant psychological burdens on individuals, insights from the social and behavioural sciences can be used to help align human behavior with the recommendations of epidemiologists and public health experts. Here we discuss evidence from a selection of research topics relevant to pandemics, including work on navigating threats, social and cultural influences on behaviour, science communication, moral decision-making, leadership, and stress and coping. In each section, we note the nature and quality of prior research, including uncertainty and unsettled issues. We identify several insights for effective response to the COVID-19 pandemic, and also highlight important gaps researchers should move quickly to fill in the coming weeks and months.
  🖺 Full Text HTML: Using social and behavioural science to support COVID-19 pandemic response
• Social and moral psychology of COVID-19 across 69 countries -
  The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behavior change. To help scholars better understand the social and moral psychology behind public health behavior, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of individual differences and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
  🖺 Full Text HTML: Social and moral psychology of COVID-19 across 69 countries
• Letter to the Editors of Psychological Science: Meta-Analysis Reveals that Accuracy Nudges Have Little to No Effect for U.S. Conservatives: Regarding Pennycook et al. (2020) -
  According to recent work, subtly nudging people to think about accuracy can reduce the sharing of COVID-19 misinformation online (Pennycook et al., 2020). The authors argue that inattention to accuracy is a key factor behind the sharing of misinformation. They further argue that “partisanship is not, apparently, the key factor distracting people from considering accuracy on social media” (p. 777). However, our meta-analysis of data from this paper and other similar papers finds that partisanship is indeed a key factor underlying accuracy judgments on social media. Specifically, our meta-analysis suggests that the effectiveness of the accuracy nudge intervention depends on partisanship such that it has little to no effect for U.S. conservatives or Republicans. This changes one of Pennycook and colleague’s (2020) central conclusions by revealing that partisanship matters considerably for the success of this intervention. Further, since U.S. conservatives and Republicans are far more likely to share misinformation than U.S. liberals and Democrats (Guess et al., 2019; Lawson & Kakkar, 2021; Osmundsen, 2021), this intervention may be ineffective for those most likely to spread fake news.
  🖺 Full Text HTML: Letter to the Editors of Psychological Science: Meta-Analysis Reveals that Accuracy Nudges Have Little to No Effect for U.S. Conservatives: Regarding Pennycook et al. (2020)
• National Narcissism and the Belief and the Dissemination of Conspiracy Theories During the COVID-19 Pandemic: Evidence From 56 Countries -
  Conspiracy theories related to COVID-19 have propagated around the globe, leading the World Health Organization to declare the spread of misinformation an ‘Infodemic’. We tested the hypothesis that national narcissism —a belief in the greatness of one’s nation that requires external recognition— is associated with the spread of conspiracy theories during the COVID-19 pandemic. In two large-scale national surveys (NTotal = 950) conducted in the US and the UK, and secondary analysis of data from 56 countries (N = 50,757), we found a robust, positive relationship between national narcissism and proneness to believe and disseminate conspiracy theories related to COVID-19. Further, belief in COVID-19 conspiracy theories was related to less engagement in health behaviors and less support for public-health policies to combat COVID-19. Our findings illustrate the importance of social identity factors in the spread of conspiracy theories and provide insights into the psychological processes underlying the COVID-19 pandemic.
  🖺 Full Text HTML: National Narcissism and the Belief and the Dissemination of Conspiracy Theories During the COVID-19 Pandemic: Evidence From 56 Countries

From Clinical Trials

• Homologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition:   COVID-19
  Intervention:   Biological: SARS-CoV-2 Subunit Recombinant Protein Vaccine
  Sponsor:   PT Bio Farma
  Not yet recruiting

• Role of Ivermectin and Colchicine in Treatment of COVID-19: Randomized Controlled Clinical Trial - Condition:   COVID-19
  Interventions:   Drug: Ivermectin Tablets;   Drug: Colchicine 0.5 MG;   Drug: Standared managment
  Sponsor:   Ain Shams University
  Completed

• A Study to Evaluate the Immunogenicity and Safety of A Recombinant Protein COVID-19 Vaccine as Booster Vaccines - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01E-2;   Biological: SCTV01E
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3) - Condition:   COVID-19
  Interventions:   Drug: theophylline;   Drug: Placebo
  Sponsor:   Washington University School of Medicine
  Recruiting

• Developing an Effective Intervention to Address Post-Corona-Virus-Disease-2019 Balance Disorders, Weakness and Muscle Fatigue in Individuals Aged 65+ - Condition:   COVID-19
  Intervention:   Device: Resistance Training
  Sponsor:   Józef Piłsudski University of Physical Education
  Recruiting

• Multimodal Long Covid19 - Condition:   Long COVID-19 Syndrome
  Intervention:   Other: Multimodal intervention in Long Covid19
  Sponsors:   Universidad de Magallanes;   Teaching Assistance and Research Center of the University of Magallanes CADI-UMAG;   Clinical Hospital Dr. Lautaro Navarro Avaria
  Active, not recruiting

• COVID-19 Trial of the Candidate Vaccine MVA-SARS-2-S in Adults - Condition:   Covid19
  Interventions:   Biological: MVA-SARS-2-S;   Other: Placebo
  Sponsors:   Universitätsklinikum Hamburg-Eppendorf;   German Center for Infection Research;   Philipps University Marburg Medical Center;   Ludwig-Maximilians - University of Munich;   University Hospital Tuebingen;   CTC-NORTH
  Withdrawn

• Treatment of Long COVID (TLC) Feasibility Trial - Condition:   COVID-19
  Interventions:   Drug: Low-dose Naltrexone (LDN);   Drug: Cetirizine;   Drug: Famotidine;   Drug: LDN Placebo;   Drug: Cetirizine Placebo;   Drug: Famotidine Placebo
  Sponsors:   Emory University;   CURE Drug Repurposing Collaboratory (CDRC)
  Not yet recruiting

• Efficiency and Safety of Paxlovid for COVID-19 Patients With Severe Chronic Kidney Disease - Conditions:   COVID-19;   Renal Insufficiency, Chronic
  Intervention:   Drug: Nirmatrelvir/ritonavir
  Sponsor:   Chinese PLA General Hospital
  Recruiting

• Safety, Efficacy, and Dosing of VIX001 in Patients With Neurological Symptoms of Post Acute COVID-19 Syndrome (PACS). - Conditions:   Post-Acute COVID-19 Syndrome;   Cognitive Impairment;   Neurological Complication
  Intervention:   Drug: VIX001
  Sponsor:   Neobiosis, LLC
  Not yet recruiting

• Effects of Music Combined With Sports Games on Alleviating Psychological Stress, Anxiety and Mental Energy Among Adolescents During COVID-19 Pandemic in Lanzhou Gansu Province China - Conditions:   Stress;   Anxiety and Fear
  Interventions:   Behavioral: Music intervention only;   Behavioral: Sports games intervention only;   Behavioral: Music and sports games intervention
  Sponsor:   Wu Jiarun
  Completed

• A Clinical Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression - Conditions:   COVID 19 Disease;   Mild to Moderate COVID 19 Disease;   SARS-CoV-2;   Infectious Disease;   Severe Acute Respiratory Syndrome Coronavirus 2
  Interventions:   Drug: Tafenoquine Oral Tablet;   Drug: Placebo
  Sponsor:   60P Australia Pty Ltd
  Not yet recruiting

• A Study to Evaluate the Efficacy, Safety, Tolerability and PK of SNS812 in Mild to Moderate COVID-19 Patients - Condition:   Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (Disorder)
  Interventions:   Drug: MBS-COV;   Drug: Placebo
  Sponsor:   Oneness Biotech Co., Ltd.
  Not yet recruiting

• Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19 - Conditions:   Asthenia;   COVID-19;   Functional MRI;   Cognitive Impairment
  Interventions:   Other: Structural and functional MRI;   Drug: Ethyl methyl hydroxypyridine succinate + Meldonium;   Drug: Placebo
  Sponsor:   Promomed, LLC
  Completed

• NDV-HXP-S Vaccine Clinical Trial (COVIVAC) - Condition:   COVID-19
  Intervention:   Biological: COVIVAC vaccine
  Sponsors:   Institute of Vaccines and Medical Biologicals, Vietnam;   National Institute of Hygiene and Epidemiology (NIHE), Vietnam;   Center for Disease Control of Thai Binh Province, Vietnam
  Completed

From PubMed

• SARS-CoV-2 Nsp1 regulates translation start site fidelity to promote infection - A better mechanistic understanding of virus-host interactions can help reveal vulnerabilities and identify opportunities for therapeutic interventions. Of particular interest are essential interactions that enable production of viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses and reporter assays to detect changes in polysome composition and protein synthesis during SARS-CoV-2 (CoV2) infection. We identify…

• Seasonal coronavirus infections trigger NLRP3 inflammasome activation in macrophages but is therapeutically targetable - Seasonal coronaviruses widely circulate in the global population, and severe complications can occur in specific vulnerable populations. Little is known on their pathogenic mechanisms and no approved treatment is available. Here, we present anecdotal evidence that the level of IL-1β, a hallmark of inflammasome activation, appears elevated in a subset of seasonal coronavirus infected patients. We found that cultured human macrophages support the full life cycle of three cultivatable seasonal…

• Proxalutamide reduces SARS-CoV-2 infection and associated inflammatory response - Early in the COVID-19 pandemic, data suggested that males had a higher risk of developing severe disease and that androgen deprivation therapy might be associated with protection. Combined with the fact that TMPRSS2 (transmembrane serine protease 2), a host entry factor for the SARS-CoV-2 virus, was a well-known androgen-regulated gene, this led to an upsurge of research investigating androgen receptor (AR)-targeting drugs. Proxalutamide, an AR antagonist, was shown in initial clinical studies…

• Exploring epigenetic drugs as potential inhibitors of SARS-CoV-2 main protease: a docking and MD simulation study - The COVID-19 pandemic has caused havoc around the globe since 2019 and is considered the largest global epidemic of the twentieth century. Although the first antiviral drug, Remdesivir, was initially introduced against COVID‑19, virtually no tangible therapeutic drugs exist to treat SARS-CoV-2 infection. FDA-approved Paxlovid (Nirmatrelvir supplemented by Ritonavir) was recently announced as a promising drug against the SARS-CoV-2 major protease (M^(pro)). Here we report for the first time the…

• Inhibition of Cysteine Proteases via Thiol-Michael Addition Explains the Anti-SARS-CoV-2 and Bioactive Properties of Arteannuin B - Artemisia annua is the plant that produces artemisinin, an endoperoxide-containing sesquiterpenoid used for the treatment of malaria. A. annua extracts, which contain other bioactive compounds, have been used to treat other diseases, including cancer and COVID-19, the disease caused by the virus SARS-CoV-2. In this study, a methyl ester derivative of arteannuin B was isolated when A. annua leaves were extracted with a 1:1 mixture of methanol and dichloromethane. This methyl ester was thought to…

• M^pro-targeted anti-SARS-CoV-2 inhibitor-based drugs - The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global health emergency. The main protease is an important drug target in coronaviruses. It plays an important role in the processing of viral RNA-translated polyproteins and is highly conserved in the amino acid sequence and three-dimensional structure, making it a good drug target for which several small molecule inhibitors are available. This paper describes the various anti-severe acute respiratory syndrome…

• New perspective on the immunomodulatory activity of ginsenosides: Focus on effective therapies for post-COVID-19 - More than 700 million confirmed cases of Coronavirus Disease-2019 (COVID-19) have been reported globally, and 10-60% of patients are expected to exhibit “post-COVID-19 symptoms,” which will continue to affect human life and health. In the absence of safer, more specific drugs, current multiple immunotherapies have failed to achieve satisfactory efficacy. Ginseng, a traditional Chinese medicine, is often used as an immunomodulator and has been used in COVID-19 treatment as a tonic to increase…

• Terpenoid phytocompounds from mangrove plant Xylocarpus moluccensis as possible inhibitors against SARS-CoV-2: In silico strategy - COVID-19 shook the world during the pandemic, where the climax it reached was vaccine manufacturing at an unfathomable pace. Alternative promising solutions to prevent infection from SARS-CoV-2 and its variants will remain crucial in the years to come. Due to its key role in viral replication, the major protease (Mpro) enzyme of SARS-CoV-2 can be an attractive therapeutic target. In the present work, natural terpenoids from mangrove medicinal plant Xylocarpus moluccensis (Lam.) M. Roem. were…

• ‘Pterocephalodes hookeri-Onosma hookeri’ decoction protects against LPS-induced pulmonary inflammation via inhibiting TLR4/ NF-κB signaling pathway - CONCLUSION: In summary, the combination therapy of ‘P-O’ exhibited good antioxidant activity and anti-inflammatory activity in vitro, as well as a therapeutic effect against pulmonary inflammation in vivo. These findings provide evidence for the clinical application of ‘P-O’ and offer new approaches for treating pneumonia.

• Intranasal insulin - effects on the sense of smell - Intranasal insulin (IN) administration is a promising way to deliver the peptide to the central nervous system (CNS), bypassing the blood-brain-barrier and gastrointestinal absorption inhibition. IN receptors are localized in the olfactory mucosa and the brain, mainly in the olfactory bulb, hypothalamus, hippocampus, amygdala, cerebral cortex, and cerebellum. The pleiotropic mechanism of insulin action is characterized by its anti-inflammatory properties, antithrombotic, vasodilatory, and…

• SARS-CoV-2 spike protein induces lung endothelial cell dysfunction and thrombo-inflammation depending on the C3a/C3a receptor signalling - The spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can interact with endothelial cells. However, no studies demonstrated the direct effect of the spike protein subunit 1 (S1) in inducing lung vascular damage and the potential mechanisms contributing to lung injury. Here, we found that S1 injection in mice transgenic for human angiotensin converting enzyme 2 (ACE2) induced early loss of lung endothelial thromboresistance at 3 days, as revealed by thrombomodulin loss…

• SARS-CoV-2 spike protein receptor-binding domain perturbates intracellular calcium homeostasis and impairs pulmonary vascular endothelial cells - Exposure to the spike protein or receptor-binding domain (S-RBD) of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular endotheliopathy. In this study, angiotensin-converting enzyme 2 humanized inbred (hACE2 Tg) mice and cultured pulmonary vascular endothelial cells were used to investigate how spike protein/S-RBD impacts pulmonary vascular endothelium. Results show that S-RBD leads to acute-to-prolonged induction of the intracellular free calcium concentration…

• Immunothrombosis and its underlying biological mechanisms - The evolutionary conserved link between coagulation and innate immunity is a biological process characterized by the thrombosis formation stimulus of immune cells and specific thrombosis-related molecules. In physiological settings, the relationship between the immune system and thrombosis facilitates the recognition of pathogens and damaged cells and inhibits pathogen proliferation. However, when deregulated, the interplay between hemostasis and innate immunity becomes a pathological process…

• CHO-produced RBD-Fc subunit vaccines with alternative adjuvants generate immune responses against SARS-CoV-2 - Subunit vaccines feature critical advantages over other vaccine platforms such as stability, price, and minimal adverse effects. To maximize immunological protection of subunit vaccines, adjuvants are considered as main components that are formulated within the subunit vaccine. They can modulate adverse effects and enhance immune outcomes. However, the most suitable formulation providing the best immunological outcomes and safety are still under investigation. In this report, we combined…

• Determining the clinical and cost-effectiveness of nasal sprays and a physical activity and stress management intervention to reduce respiratory tract infections in primary care: A protocol for the ‘Immune Defence’ randomised controlled trial - BACKGROUND: Most adults in the UK experience at least one viral respiratory tract infection (RTI) per year. Individuals with comorbidities and those with recurrent RTIs are at higher risk of infections. This can lead to more severe illness, worse quality of life and more days off work. There is promising evidence that using common nasal sprays or improving immune function through increasing physical activity and managing stress, may reduce the incidence and severity of RTIs.

From Patent Search