Covid-19 Sentry

Contents

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

From Preprints

• Assessment for the seasonality of Covid-19 should focus on ultraviolet radiation and not ‘warmer days’ -
  More attention should be paid to ultraviolet radiation for the seasonality of Covid-19, based on the previous SARS and MERS epidemics, and not the ‘warmer days’ of summer.
  🖺 Full Text HTML: Assessment for the seasonality of Covid-19 should focus on ultraviolet radiation and not ‘warmer days’
• Protein complex heterogeneity and topology revealed by electron capture charge reduction and surface induced dissociation -
  Herein, we focus on native mass spectrometry (nMS) combined with a fast, tunable gas-phase charge reduction, electron capture charge reduction (ECCR), and illustrate its utility in the characterization of protein complex topology and glycoprotein heterogeneity. ECCR is illustrated to effectively spread the charge states of tetradecameric GroEL, illustrating Orbitrap m/z measurement out to greater than 100,000 m/z. For both the pentameric C-reactive protein and tetradecameric GroEL, our novel device combining ECCR with surface induced dissociation (SID) lowers the charge states and produces more topologically informative fragmentation. While more native-like fragmentation has previously been illustrated for complexes charge reduced by proton abstraction in solution, this is the first illustration that ECCR can lead to more native-like SID fragmentation of protein complexes. Application to protein glycosylation, one of the most common and diverse protein posttranslational modifications, is also illustrated because glycosylation is important for structural and functional properties and plays essential roles in many key biological processes. The immense heterogeneity resulting from variability in glycosylation sites and glycan composition and structure poses significant analytical challenges that hinder a mechanistic understanding of the biological role of glycosylation. Data for stabilized heavily glycosylated SARS-CoV-2 spike protein trimer and thyroglobulin dimer illustrate that ECCR enables significantly improved resolution of glycan heterogeneity. Without ECCR, the charge states of a glycoprotein complex are not resolved and average mass determination is available only through the use of charge detection mass spectrometry or mass photometry. With ECCR after narrow m/z selection, multiple glycoform m/z values are apparent, providing quick global, glycoform profiling and providing a future path for glycan localization on individual intact glycoforms (e.g., though top-down dissociation).
  🖺 Full Text HTML: Protein complex heterogeneity and topology revealed by electron capture charge reduction and surface induced dissociation
• 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

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

• Ginseng and ginsenosides on cardiovascular and pulmonary diseases; Pharmacological potentials for the coronavirus (COVID-19) - Since its outbreak in late 2019, the Coronavirus disease 2019 (COVID-19) pandemic has profoundly caused global morbidity and deaths. The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has major complications in cardiovascular and pulmonary system. The increased rate of mortality is due to delayed detection of certain biomarkers that are crucial in the development of disease. Furthermore, certain proteins and enzymes in cellular signaling pathways play an…

• Inhibition of SARS-CoV-2 infection by Porphyromonas gingivalis and the oral microbiome - The COVID-19 pandemic persists despite the availability of vaccines, and it is therefore crucial to develop new therapeutic and preventive approaches. In this study, we investigated the potential role of the oral microbiome in SARS-CoV-2 infection. Using an in vitro SARS-CoV-2 pseudovirus infection assay, we found a potent inhibitory effect exerted by Porphyromonas gingivalis on SARS-CoV-2 infection mediated by known P. gingivalis compounds such as phosphoglycerol dihydroceramide (PGDHC) and…

• An allosteric mechanism for potent inhibition of SARS-CoV-2 main proteinase - The main proteinase (M^(pro)) of SARS-CoV-2 plays a critical role in cleaving viral polyproteins into functional proteins required for viral replication and assembly, making it a prime drug target for COVID-19. It is well known that noncompetitive inhibition offers potential therapeutic options for treating COVID-19, which can effectively reduce the likelihood of cross-reactivity with other proteins and increase the selectivity of the drug. Therefore, the discovery of allosteric sites of M^(pro)…

• NLRC5/MHC class I transactivator: A key target for immune escape by SARS-CoV-2 - Antigen presentation to CD8+ T cells by MHC class I molecules is essential for host defense against viral infections. Various mechanisms have evolved in multiple viruses to escape immune surveillance and defense to support viral proliferation in host cells. Through in vitro SARS-CoV-2 infection studies and analysis of COVID-19 patient samples, we found that SARS-CoV-2 suppresses the induction of the MHC class I pathway by inhibiting the expression and function of NLRC5, a major transcriptional…

• Quantitative Assessment of Energetic Contributions of Residues in a SARS-CoV-2 Viral Enzyme/Nanobody Interface - The highly conserved protease enzyme from SARS-CoV-2 (M^(Pro)) is crucial for viral replication and is an attractive target for the design of novel inhibitory compounds. M^(Pro) is known to be conformationally flexible and has been stabilized in an extended conformation in a complex with a novel nanobody (NB2B4), which inhibits the dimerization of the enzyme via binding to an allosteric site. However, the energetic contributions of the nanobody residues stabilizing the M^(Pro)/nanobody interface…

• Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury - SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others’, has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein-resulted in inflammation in…

• 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.

From Patent Search