Covid-19 Sentry

Contents

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

From Preprints

• In silico genomic surveillance by CoVerage predicts and characterizes SARS-CoV-2 Variants of Interest -
  Rapidly evolving viral pathogens such as SARS-CoV-2 continuously accumulate amino acid changes, some of which affect transmissibility, virulence or improve the virus' ability to escape host immunity. Since the beginning of the pandemic and establishment of SARS-CoV-2 as a human pathogen, multiple lineages with concerning phenotypic alterations, so called Variants of Concern (VOCs), have emerged and risen to predominance. To optimize public health management and to ensure the continued efficacy of vaccines, the early detection of such variants of interest is essential. Therefore, large-scale viral genomic surveillance programs have been initiated worldwide, with data being deposited in public repositories in a timely manner. However, technologies for their continuous interpretation are currently lacking. Here, we describe the CoVerage system (www.sarscoverage.org) for viral genomic surveillance, which continuously predicts and characterizes novel and emerging potential Variants of Interest (pVOIs) together with their antigenic and evolutionary alterations. Using the establishment of Omicron and its current sublineages as an example, we demonstrate how CoVerage can be used to quickly identify and characterize such variants. CoVerage can facilitate the timely identification and assessment of future SARS-CoV-2 Variants of Concern.
  🖺 Full Text HTML: In silico genomic surveillance by CoVerage predicts and characterizes SARS-CoV-2 Variants of Interest
• Rapid Degradation of the Human ACE2 Receptor Upon Binding and Internalization of SARS-Cov-2-Spike-RBD Protein -
  It is widely accepted that the SARS-CoV-2 betacoronavirus infects humans through binding the human Angiotensin Receptor 2 (ACE2) that lines the nasal cavity and lungs, followed by import into a cell utilizing the Transmembrane Protease, Serine 2 (TMPRSS2) cofactor. ACE2 binding is mediated by an approximately 200-residue portion of the SARS-CoV-2 extracellular spike protein, the receptor binding domain (RBD). Robust interactions are shown using a novel cell-based assay between an RBD membrane tethered-GFP fusion protein and the membrane bound ACE2-Cherry fusion protein. Several observations were not predicted including, quick and sustained interactions leading to internalization of RBD fusion protein into the ACE2 cells and rapid downregulation of the ACE2-Cherry fluorescence. Targeted mutation in the RBD disulfide Loop 4 led to a loss of internalization for several variants tested. However, a secreted RBD did not cause ACE2 downregulation of ACE2-Cherry fluorescence. Thus, the membrane associated form of RBD found on the viral coat may have long-term system wide consequences on ACE2 expressing cells.
  🖺 Full Text HTML: Rapid Degradation of the Human ACE2 Receptor Upon Binding and Internalization of SARS-Cov-2-Spike-RBD Protein
• Coronavirus Spike-RBD Variants Differentially Bind to the Human ACE2 Receptor -
  The SARS-CoV-2 betacoronavirus infects people through binding the human Angiotensin Receptor 2 (ACE2), followed by import into a cell utilizing the Transmembrane Protease, Serine 2 (TMPRSS2) and Furin cofactors. Analysis of the SARS-CoV-2 extracellular spike protein has suggested critical amino acids necessary for binding within a 197-residue portion, the receptor binding domain (RBD). A cell-based assay between a membrane tethered RBD-GFP fusion protein and the membrane bound ACE2-Cherry fusion protein allowed for mutational intersection of both RBD and ACE2 proteins. Data shows Omicron BA.1 and BA.2 variants have altered dependency on the amino terminus of ACE2 protein and suggests multiple epitopes on both proteins stabilize their interactions at the Nt and internal region of ACE2. In contrast, the H-CoV-NL63 RBD is only dependent on the ACE2 internal region for binding. A peptide inhibitor approach to this internal region thus far have failed to block binding of RBDs to ACE2, suggesting that several binding regions on ACE2 are sufficient to allow functional interactions. In sum, the RBD binding surface of ACE2 appears relatively fluid and amenable to bind a range of novel variants.
  🖺 Full Text HTML: Coronavirus Spike-RBD Variants Differentially Bind to the Human ACE2 Receptor
• Antigenicity assessment of SARS-CoV-2 saltation variant BA.2.87.1 -
  The recent emergence of a SARS-CoV-2 saltation variant, BA.2.87.1, which features 65 spike mutations relative to BA.2, has attracted worldwide attention. In this study, we elucidate the antigenic characteristics and immune evasion capability of BA.2.87.1. Our findings reveal that BA.2.87.1 is more susceptible to XBB-induced humoral immunity compared to JN.1. Notably, BA.2.87.1 lacks critical escaping mutations in the receptor binding domain (RBD) thus allowing various classes of neutralizing antibodies (NAbs) that were escaped by XBB or BA.2.86 subvariants to neutralize BA.2.87.1, although the deletions in the N-terminal domain (NTD), specifically 15-23del and 136-146del, compensate for the resistance to humoral immunity. Interestingly, several neutralizing antibody drugs have been found to restore their efficacy against BA.2.87.1, including SA58, REGN-10933 and COV2-2196. Hence, our results suggest that BA.2.87.1 may not become widespread until it acquires multiple RBD mutations to achieve sufficient immune evasion comparable to that of JN.1.
  🖺 Full Text HTML: Antigenicity assessment of SARS-CoV-2 saltation variant BA.2.87.1
• Resolution of SARS-CoV-2 infection in human lung tissues is driven by extravascular CD163+ monocytes -
  The lung-resident immune mechanisms driving resolution of SARS-CoV-2 infection in humans remain elusive. Using mice co-engrafted with a genetically matched human immune system and fetal lung xenograft (fLX), we mapped the immunological events defining resolution of SARS-CoV-2 infection in human lung tissues. Viral infection is rapidly cleared from fLX following a peak of viral replication. Acute replication results in the emergence of cell subsets enriched in viral RNA, including extravascular inflammatory monocytes (iMO) and macrophage-like T-cells, which dissipate upon infection resolution. iMO display robust antiviral responses, are transcriptomically unique among myeloid lineages, and their emergence associates with the recruitment of circulating CD4+ monocytes. Consistently, mice depleted for human CD4+ cells but not CD3+ T-cells failed to robustly clear infectious viruses and displayed signatures of chronic infection. Our findings uncover the transient differentiation of extravascular iMO from CD4+ monocytes as a major hallmark of SARS-CoV-2 infection resolution and open avenues for unravelling viral and host adaptations defining persistently active SARS-CoV-2 infection.
  🖺 Full Text HTML: Resolution of SARS-CoV-2 infection in human lung tissues is driven by extravascular CD163+ monocytes
• Human Cytokine and Coronavirus Nucleocapsid Protein Interactivity Using Large-Scale Virtual Screens -
  Understanding the interactions between SARS-CoV-2 and the human immune system is paramount to the characterization of novel variants as the virus co-evolves with the human host. In this study, we employed state-of-the-art molecular docking tools to conduct large-scale virtual screens, predicting the binding affinities between 64 human cytokines against 17 nucleocapsid proteins from six betacoronaviruses. Our comprehensive in silico analyses reveal specific changes in cytokine-nucleocapsid protein interactions, shedding light on potential modulators of the host immune response during infection. These findings offer valuable insights into the molecular mechanisms underlying viral pathogenesis and may guide the future development of targeted interventions. This manuscript serves as insight into the comparison of deep learning based AlphaFold2-Multimer and the semi-physicochemical based HADDOCK for protein-protein docking. We show the two methods are complementary in their predictive capabilities. We also introduce a novel algorithm for rapidly assessing the binding interface of protein-protein docks using graph edit distance: graph-based interface residue assessment function (GIRAF). The high-performance computational framework presented here will not only aid in accelerating the discovery of effective interventions against emerging viral threats, but extend to other applications of high throughput protein-protein screens.
  🖺 Full Text HTML: Human Cytokine and Coronavirus Nucleocapsid Protein Interactivity Using Large-Scale Virtual Screens
• Who deserves economic relief - Preprint T Hilmar March 2024 -
  The economic shock of the Covid-19 crisis has disproportionately impacted small businesses and the self-employed. Around the globe, their survival during the pandemic often relied heavily on government assistance. This article explores how economic relief to business is understood through the lens of deservingness in the public. It examines the case of Germany, where the government has responded to the pandemic by implementing an extensive support program. Notably, in this context, the self-employed are typically outsiders to the state insurance system. Combining computational social science methods and a qualitative analysis, the article focuses on the debate about direct subsidies on the social media platform Twitter/X between March 2020 and June 2021. It traces variation in the patterns of claim making in what is a rich debate about pandemic state support, finding that this discourse is characterised by the concern that economic relief threatens to blur existing boundaries of worth in society. The reciprocity principle of deservingness theory is pivotal in asserting business identities in times of crisis, yet it also reveals a fundamentally ambiguous relationship with the principle of need. Additionally, the claim of justice-as-redress, as a novel dimension of reciprocity, surfaces as an important theme in this debate.
  🖺 Full Text HTML: Who deserves economic relief - Preprint T Hilmar March 2024
• Protein design for evaluating vaccines against future viral variation -
  Recurrent waves of SARS-CoV-2 infection, driven by the periodic emergence of new viral variants, highlight the need for vaccines and therapeutics that remain effective against future strains. Yet, our ability to proactively evaluate such therapeutics is limited to assessing their effectiveness against previous or circulating variants, which may differ significantly in their antibody escape from future viral evolution. To address this challenge, we develop a deep learning method to predict the effect of mutations on fitness and escape from neutralizing antibodies. We use this model to engineer 83 unique SARS-CoV-2 Spike proteins incorporating novel combinations of up to 46 amino acid changes relative to the ancestral B.1 variant. The designed constructs were infectious and evaded neutralization by nine well-characterized panels of human polyclonal anti-SARS-CoV-2 immune sera (from vaccinated, boosted, bivalent boosted, and breakthrough infection individuals). Designed constructs on contemporary SARS-CoV-2 strains displayed similar levels of antibody escape and similar antigenic profiles as variants seen subsequently (up to 12 months later) during the COVID-19 pandemic despite differences in exact mutations. Our approach provides targeted panels of antigenically diverse escape variants for an early evaluation of the protective ability of vaccines and therapeutics to inhibit not only currently circulating but also future variants. This approach is generalizable to other viral pathogens.
  🖺 Full Text HTML: Protein design for evaluating vaccines against future viral variation
• Will Europe be forged in crises? The impact of the Covid-19 and Ukraine crises on EU actorness -
  In this paper, we study the effect of crises on EU actorness, defined as the EU’s capacity to defend its interests and values at the global level. Our research focuses on two major crises, the Covid-19 crisis and the 2022 Russian invasion of Ukraine. Drawing on a process-tracing approach, we analyse four of the Union’s policy initiatives that were proposed, negotiated and implemented to respond to these crises: joint vaccine procurement, common gas purchases, and the COVAX and FARM initiatives. The paper assesses the outcomes of these four initiatives and discusses the extent to which these initiatives led to the development of EU actorness and the achievement of common objectives. The analysis identifies the degree of internal cohesion, and how it is influenced by specific crises, as a key factor in fostering or hampering EU actorness in different policy fields. It also shows that the formal distribution of competences between the EU and the member states in specific policy areas matters little in crisis times, as the EU can resort to emergency competences in such situations. The findings of this paper contribute to the literature on EU actorness and equally provide some insights on policy legacies and learning.
  🖺 Full Text HTML: Will Europe be forged in crises? The impact of the Covid-19 and Ukraine crises on EU actorness
• Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity -

  Since the COVID-19 pandemic began in 2020, viral sequencing has documented 131 individual mutations in the viral spike protein across 48 named variants. To determine the ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution, we assessed the neutralization potency of sera from 76 vaccine recipients collected after 2 to 6 immunizations against a comprehensive panel of mutations observed during the pandemic. Remarkably, while many individual mutations that emerged between 2020 and 2022 exhibit escape from sera following primary vaccination, few escape boosted sera. However, progressive loss of neutralization was observed across newer variants, irrespective of vaccine doses. Importantly, an updated XBB.1.5 booster significantly increased titers against newer variants but not JN.1. These findings demonstrate that seasonal boosters improve titers against contemporaneous strains, but novel variants continue to evade updated mRNA vaccines, demonstrating the need for novel approaches to adequately control SARS-CoV-2 transmission.

  🖺 Full Text HTML: Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity
• The importance of mothers: The social transmission of COVID-19 vaccination attitudes and uptake -

  The global fight against the COVID-19 pandemic has underscored the critical importance of widespread vaccination to mitigate the impact of the virus on public health. The current study aimed to investigate which social influences might be most important for predicting attitudes towards COVID-19 vaccination and vaccine uptake among young students in the UK. We focused on the cultural evolution and social transmission aspects, i.e., parent-to-child versus peer-to-peer, of attitudes and vaccine uptake during the COVID-19 pandemic.  A sample of 192 UK students (aged 18 to 35 years old) filled in an online survey including measures for attitudes towards COVID-19 vaccination and vaccine uptake and/or intention, age, and gender. Participants were also asked about their mother’s, father’s, and best friend’s attitudes towards COVID-19 vaccination and vaccine uptake. Finally, they provided a subjective measure of the quality relationship with their parents. Overall, our results suggest that both parents and very close friends are important agents in understanding the students’ attitudes towards COVID-19 vaccination and vaccine uptake. More specifically, our findings suggest the mother’s vaccine uptake as the most salient predictor of students’ attitudes towards COVID-19 vaccination and vaccine uptake, particularly when the students disclose having a positive relationship with their parents. In cases where students’ experience negative relationship with their parents, the best friend’s vaccine uptake may supersede the mother’s influence. Despite these nuances, a general trend emerges from our data suggesting that vaccine uptake could be primarily guided by vertical transmission (i.e., parent to child). Our results have the potential to influence public health strategies, communication campaigns, and targeted interventions to enhance vaccination uptake. Identifying key social predictors can enable policymakers and health authorities to tailor vaccination promotion efforts towards mothers’ and peers’ vaccine uptake to increase overall positive attitudes and vaccine uptake among young people.

  🖺 Full Text HTML: The importance of mothers: The social transmission of COVID-19 vaccination attitudes and uptake
• Predictors of mortality among COVID-19 patients at Kilimanjaro Christian Medical Centre in Northern Tanzania: A hospital-based retrospective cohort study -

  Background COVID-19 disease is a global public health disaster causing a range of social, economic, and healthcare difficulties, border restrictions, high human loss, lockdown, and transportation challenges. Despite it being a global pandemic, there are few studies conducted in Tanzania to examine the predictors of mortality. This disease has caused a significant number of mortalities worldwide but literature shows low mortality and better survival in Africa than in other WHO regions. Therefore, this study aimed to determine the predictors of mortality among COVID-19 patients at KCMC Hospital in Northern Tanzania. Methodology This was the hospital-based retrospective cohort study, conducted at KCMC Hospital in Northern Tanzania among all admitted patients with confirmed COVID-19, from 10th March 2020 to 26th January 2022. The main study event was COVID-19 mortality. The predictors of mortality were determined by using the Weibull survival regression model and the statistically significant results were declared at a p-value of <0.05. Results A total of 547 confirmed COVID-19 patient records were included in the study. Their median age was 63 (IQR; 53-83), about 60% were aged 60 years and above, and 56.7% were males. The most common clinical features were; fever (60.8%), a severe form of the disease (44.4%), difficulty in breathing (73.3%), chest pain (46.1%), and generalized body weakness (71.3%). Of all participants, over one-third (34.6%) died (95%CI; 0.31-0.39). The median survival time was 7 days (IQR; 3-12). The overall mortality rate was 32.33 per 1000 person-days while the independent predictors of higher mortality risk were age ≥60 years (AHR=2.01; 95%CI 1.41-2.87; P<0.001), disease severity (AHR=4.44; 95%CI 2.56-7.73; P<0.001) and male sex (AHR=1.28; 95%CI; 0.93-1.73; P=0.128). Conclusion Mortality was higher in elderly male patients, with a severe form of the disease and those with any comorbidities. Therefore, more attention should be provided to older patients including uptake of the current vaccine and ensuring standard and supportive care at primary health facilities is available.

  🖺 Full Text HTML: Predictors of mortality among COVID-19 patients at Kilimanjaro Christian Medical Centre in Northern Tanzania: A hospital-based retrospective cohort study
• Accelerated brain age in young to early middle-aged adults after mild to moderate COVID-19 infection -

  Cognitive decline is a common adverse effect of the Coronavirus Disease of 2019 (COVID-19), particularly in the post-acute disease phase. The mechanisms of cognitive impairment after COVID-19 (COGVID) remain unclear, but neuroimaging studies provide evidence of brain changes, many that are associated with aging. Therefore, we calculated Brain Age Gap (BAG), which is the difference between brain age and chronological age, in a cohort of 25 mild to moderate COVID-19 survivors (did not experience breathlessness, pneumonia, or respiratory/organ failure) and 24 non-infected controls (mean age = 30 +/- 8) using magnetic resonance imaging (MRI). BAG was significantly higher in the COVID-19 group (F = 4.22, p = 0.046) by 2.65 years. Additionally, 80% of the COVID-19 group demonstrated an accelerated BAG compared to 13% in the control group (X2 = 20.0, p < 0.001). Accelerated BAG was significantly correlated with lower cognitive function (p < 0.041). Females in the COVID-19 group demonstrated a 99% decreased risk of accelerated BAG compared to males (OR = 0.015, 95% CI: 0.001 to 0.300). There was also a small (1.4%) but significant decrease in risk for accelerated BAG associated with longer time since COVID-19 diagnosis (OR = 0.986, 95% CI: 0.977 to 0.995). Our findings provide a novel biomarker of COGVID and point to accelerated brain aging as a potential mechanism of this adverse effect. Our results also offer further insight regarding gender-related disparities in cognitive morbidity associated with COVID-19.

  🖺 Full Text HTML: Accelerated brain age in young to early middle-aged adults after mild to moderate COVID-19 infection
• COVID-19 Vaccination Booster Uptake Is Related to End of Pandemic Perception: Population-Based Survey in Four Provinces in Indonesia -

  Global COVID-19 booster vaccination uptake has been low, particularly in low-middle-income countries (LMICs). However, studies on the determinants of COVID-19 booster vaccination remain limited, especially in LMIC settings. This study aims to describe the determinants of COVID-19 booster vaccination uptake in an LMIC context. We analyzed data from a cross-sectional survey that was conducted in September 2022 in four provinces in Indonesia. Participants (n=2,223) were recruited using multiple-stage cluster sampling. Multivariable logistic regression analysis was used to identify factors associated with booster vaccination status. The proportion of COVID-19 booster vaccination among fully vaccinated adults was 29.5%, while fear of transmission (12.4%) and perceived risk of getting a COVID-19 infection (33.5%) were low. Multivariable analysis showed that people living on Java Island (aOR: 2.45, 95% CI: 1.87-3.24), living in the urban area (aOR: 2.04, 95% CI: 1.60-2.61), being an employee in the formal sector (aOR: 3.99, 95% CI: 1.93 - 8.58), experiencing a side effect from previous vaccination (aOR: 1.71, 95% CI: 1.40-2.09), having a history of SARS-COV2 infection (aOR: 2.10, 95%CI: 1.27-3.50), having perception on the upcoming new wave of COVID-19 (aOR: 1.37, 95% CI: 1.07 -1.76), and believing the pandemic has not ended (aOR: 1.29, 95% CI: 1.01, 1.64) were associated with booster shot uptake. Low educational level (aOR: 0.6, 95% CI: 0.39-0.93) inhibited booster vaccination uptake. Current booster dose coverage was considerably lower than the primary vaccination dosage. The low booster vaccination uptake in four provinces was associated with a belief the pandemic has no longer, which might hinder the catch up of wide-population target coverage and COVID-19 control for reduced disease severity and hospitalization. Thus, efforts need to be prioritized in reaching the COVID-19 vulnerable population, which includes elderly and those with comorbidities.

  🖺 Full Text HTML: COVID-19 Vaccination Booster Uptake Is Related to End of Pandemic Perception: Population-Based Survey in Four Provinces in Indonesia
• Community level variability in Bronx COVID-19 hospitalizations associated with differing viral variant adaptive strategies during the second year of the pandemic. -

  The Bronx, New York, exhibited unique peaks in the number of COVID-19 cases and hospitalizations compared to national trends. To determine which features of the SARS-CoV-2 virus might underpin this local disease epidemiology, we conducted a comprehensive analysis of the genomic epidemiology of the four dominant strains of SARS-CoV-2 (Alpha, Iota, Delta and Omicron) responsible for COVID-19 cases in the Bronx between March 2020 and January 2023. Genomic analysis revealed similar viral fitness for Alpha and Iota variants in the Bronx compared to nationwide data. However, Delta and Omicron variants had increased fitness within the borough. While the transmission dynamics of most variants in the Bronx corresponded with mutational fitness-based predictions of transmissibility, the Delta variant presented as an exception. Epidemiological modeling confirms Delta9s advantages of higher transmissibility, and suggested pre-existing immunity within the community counteracted Delta virulence, contributing to unexpectedly low Bronx hospitalizations compared to preceding strains. There were few novel T-cell epitope mutations in Delta compared to Iota which suggests Delta had fewer immune escape mechanisms to subvert pre-existing immunity within the Bronx. The combination of epidemiological models and quantifying amino acid changes in T-cell and antibody epitopes also revealed an evolutionary trade-off between Alphas higher transmissibility and Iotas immune evasion, potentially explaining why the Bronx Iota variant remained dominant despite the introduction of the nationwide dominant Alpha variant. Together, our study demonstrates that localized analyses and integration of orthogonal community-level datasets can provide key insights into the mechanisms of transmission and immunity patterns associated with regional COVID-19 incidence and disease severity that may be missed when analyzing broader datasets.

  🖺 Full Text HTML: Community level variability in Bronx COVID-19 hospitalizations associated with differing viral variant adaptive strategies during the second year of the pandemic.

From Clinical Trials

• COVIDVaxStories: Randomized Trial to Reduce COVID-19 Vaccine Hesitancy in Populations of Color - Conditions: Vaccine Hesitancy
  Interventions: Behavioral: Storytelling; Behavioral: Learn More (Active Comparator)
  Sponsors: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC
  Recruiting

• An E-health Psychoeducation for People With Bipolar Disorders - Conditions: Bipolar Disorder; Psychoeducation; COVID-19 Pandemic
  Interventions: Other: e-health psychoeducation
  Sponsors: University of Cagliari; Alessandra Perra
  Completed

• Sulfureous Water Therapy in Viral Respiratory Diseases - Conditions: Long-COVID; Post COVID-19 Condition; Chronic COVID-19 Syndrome; Post Acute Sequelae of COVID-19
  Interventions: Other: Inhalation of Sulfurous Thermal Water; Other: Inhalation of Sterile Distilled non-pyrogenic Water
  Sponsors: University of Roma La Sapienza; Università degli studi di Roma Foro Italico; Queen Mary University of London; Bios Prevention Srl
  Completed

• Phase 3 Study of the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine - Conditions: COVID-19
  Interventions: Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Biological: Novavax COVID-19 Vaccine; Biological: Comparator Influenza Vaccine - Fluarix; Biological: Comparator Influenza Vaccine -Fluarix High Dose; Biological: Placebo 0.9% sodium chloride for injection
  Sponsors: Novavax
  Not yet recruiting

• Evaluation of KGR Prescriptions in Suppressing COVID-19 Infection. - Conditions: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2 Infection
  Interventions: Combination Product: Kang Guan Recipe (Treat); Combination Product: Kang Guan Recipe (Placebo)
  Sponsors: Sheng-Teng Huang
  Completed

• SHEN211 Tablets for the Treatment of Mild and Moderate Novel Corona Virus Infections (COVID-19) - Conditions: COVID-19
  Interventions: Drug: SHEN211 Tablets; Procedure: Placebo for SHEN211 Tablets
  Sponsors: JKT Biopharma Co., Ltd.
  Not yet recruiting

• INAVAC Vaccine Phase III (Immunobridging Study) in Healthy Population Aged 12 to 17 Years Old - Conditions: COVID-19 Pandemic; COVID-19 Vaccines
  Interventions: Biological: INAVAC (Vaksin Merah Putih - UA-SARS CoV-2 (Vero Cell Inactivated) 5 µg
  Sponsors: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia
  Recruiting

• Immunogenicity and Safety Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults - Conditions: COVID-19
  Interventions: Biological: ARCT-2303; Biological: Influenza vaccine; Biological: Influenza vaccine, adjuvanted; Other: Placebo
  Sponsors: Arcturus Therapeutics, Inc.; Seqirus; Novotech (Australia) Pty Limited
  Not yet recruiting

• Study to Evaluate the Safety & Immunogenicity of IMNN-101 Administered in Healthy Adults Previously Vaccinated Against SARS-CoV-2 - Conditions: SARS CoV 2 Infection
  Interventions: Biological: IMNN-101
  Sponsors: Imunon
  Not yet recruiting

• Effectiveness of a Nasal Spray on Viral Respiratory Infections - Conditions: Acute Respiratory Tract Infection; Flu, Human; COVID-19; Common Cold
  Interventions: Device: Nasal Spray HSV Treatment
  Sponsors: CEN Biotech; Urgo Research, Innovation & Development
  Recruiting

From PubMed

• Indole Propionic Acid Disturbs the Normal Function of Tryptophanyl-tRNA Synthetase in Mycobacterium tuberculosis - Tuberculosis (TB) is the leading infectious disease caused by Mycobacterium tuberculosis and the second-most contagious killer after COVID-19. The emergence of drug-resistant TB has caused a great need to identify and develop new anti-TB drugs with novel targets. Indole propionic acid (IPA), a structural analog of tryptophan (Trp), is active against M. tuberculosis in vitro and in vivo. It has been verified that IPA exerts its antimicrobial effect by mimicking Trp as an allosteric inhibitor of…

• Effects of Lamiaceae family plants and their bioactive ingredients on coronavirus-induced lung inflammation - Coronaviruses (CoVs) are a family of viruses that cause infection in respiratory and intestinal systems. Different types of CoVs, those responsible for the SARS-CoV and the new global pandemic of coronavirus disease 2019 in people, have been found. Some plants were used as food additives: spices and dietary and/or medicinal purposes in folk medicine. We aimed to provide evidence about possible effects of two Lamiaceae family plants on control or treatment of CoVs-induced inflammation. The…

• Deregulation of interferon-gamma receptor 1 expression and its implications for lung adenocarcinoma progression - Interferon-gamma (IFN-γ) plays a dual role in cancer; it is both a pro- and an antitumorigenic cytokine, depending on the type of cancer. The deregulation of the IFN-γ canonic pathway is associated with several disorders, including vulnerability to viral infections, inflammation, and cancer progression. In particular, the interplay between lung adenocarcinoma (LUAD) and viral infections appears to exist in association with the deregulation of IFN-γ signaling. In this mini-review, we investigated…

• The role of N-acetylcysteine in decreasing neutrophil-lymphocyte ratio in COVID-19 patients: A double-blind, randomized controlled trial - N-acetylcysteine has antioxidant and anti-inflammatory activities that could potentially improve the clinical outcomes of coronavirus disease 2019 (COVID-19) patients. N-acetylcysteine potentially inhibits NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome and results in control oxidative stress and cytokine release in COVID-19 patients. The aim of this study was to assess the effect of N-acetylcysteine in reducing the neutrophil-lymphocyte ratio (NLR) in COVID-19 patients. A…

• Metabolic profiling of milk thistle different organs using UPLC-TQD-MS/MS coupled to multivariate analysis in relation to their selective antiviral potential - CONCLUSION: This study valorizes the importance of different S. marianum organs as wealthy sources of selective and effective antiviral candidates. This approach can be extended to unravel potentially active constituents from complex plant matrices.

• Role of Microbiota-Derived Corisin in Coagulation Activation during SARS-CoV-2 Infection - CONCLUSION: The microbiota-derived corisin is significantly increased and correlated with activation of the coagulation system during SARS-CoV-2 infection, and corisin may directly increase the procoagulant activity in epithelial, endothelial and monocytic cells.

• Risks of infection and severity of coronavirus disease 2019 in kidney transplant recipients: A single-center cohort study - CONCLUSION: In kidney transplant recipients, the infection rate and severity of COVID-19 tended to increase with higher maintenance doses of steroids. Recipients taking >5 mg of prednisolone should be considered a switch from tacrolimus to cyclosporine because cyclosporine may inhibit viral replication and reduce the risk of infection.

• Metabolic regulation of neutrophil functions in homeostasis and diseases - Neutrophils are the most abundant leukocytes in humans and play a role in the innate immune response by being the first cells attracted to the site of infection. While early studies presented neutrophils as almost exclusively glycolytic cells, recent advances show that these cells use several metabolic pathways other than glycolysis, such as the pentose phosphate pathway, oxidative phosphorylation, fatty acid oxidation, and glutaminolysis, which they modulate to perform their functions….

• Transcriptome analysis reveals organ-specific effects of 2-deoxyglucose treatment in healthy mice - CONCLUSIONS: These findings suggest that 2DG has a systemic impact that varies across organs, potentially affecting multiple pathways and functions. The study provides insights into the potential therapeutic benefits of 2DG across different diseases and highlights the importance of understanding its systemic effects for future research and clinical applications.

• Repurposing of SARS-CoV-2 compounds against Marburg Virus using MD simulation, mm/GBSA, PCA analysis, and free energy landscape - The significant mortality rate associated with Marburg virus infection made it the greatest hazard among infectious diseases. Drug repurposing using in silico methods has been crucial in identifying potential compounds that could prevent viral replication by targeting the virus’s primary proteins. This study aimed at repurposing the drugs of SARS-CoV-2 for identifying potential candidates against the matrix protein VP40 of the Marburg virus. Virtual screening was performed where the control…

• Natural products as a source of Coronavirus entry inhibitors - The COVID-19 pandemic has had a significant and lasting impact on the world. Four years on, despite the existence of effective vaccines, the continuous emergence of new SARS-CoV-2 variants remains a challenge for long-term immunity. Additionally, there remain few purpose-built antivirals to protect individuals at risk of severe disease in the event of future coronavirus outbreaks. A promising mechanism of action for novel coronavirus antivirals is the inhibition of viral entry. To facilitate…

• Antigenic drift and immunity gap explain reduction in protective responses against influenza A(H1N1)pdm09 and A(H3N2) viruses during the COVID-19 pandemic: a cross-sectional study of human sera collected in 2019, 2021, 2022, and 2023 - CONCLUSION: The observed reduction in protective antibodies against A(H1N1)pdm09 and A(H3N2) viruses post COVID-19 is best explained by antigenic drift of emerging viruses, and not waning of antibody responses in the general population. However, the absence of influenza during the pandemic resulted in an immunity gap in the youngest children. While this immunity gap was partially closed following the 2022/2023 influenza season, children with elevated risk of severe infection should be…

• Glycan-directed SARS-CoV-2 inhibition by leek extract and lectins with insights into the mode-of-action of Concanavalin A - Four years after its outbreak, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global challenge for human health. At its surface, SARS-CoV-2 features numerous extensively glycosylated spike proteins. This glycan coat supports virion docking and entry into host cells and at the same time renders the virus less susceptible to neutralizing antibodies. Given the high genetic plasticity of SARS-CoV-2 and the rapid emergence of immune escape variants, targeting the glycan shield…

• Structural Relationships to Efficacy for Prazole-Derived Antivirals - Here, an in vitro characterization of a family of prazole derivatives that covalently bind to the C73 site on Tsg101 and assay their ability to inhibit viral particle production is presented. Structurally, increased steric bulk on the 4-pyridyl of the prazole expands the prazole site on the UEV domain toward the β-hairpin in the Ub-binding site and is coupled to increased inhibition of virus-like particle production in HIV-1. Increased bulk also increased toxicity, which is alleviated by…

• BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase inhibitor, inhibits SARS-CoV-2 variants of concern and exerts synergistic antiviral activity in combination with remdesivir - Viral RNA-dependent RNA polymerase (RdRp), a highly conserved molecule in RNA viruses, has recently emerged as a promising drug target for broad-acting inhibitors. Through a Vero E6-based anti-cytopathic effect assay, we found that BPR3P0128, which incorporates a quinoline core similar to hydroxychloroquine, outperformed the adenosine analog remdesivir in inhibiting RdRp activity (EC(50) = 0.66 µM and 3 µM, respectively). BPR3P0128 demonstrated broad-spectrum activity against various severe…

From Patent Search