- Ecological systems contributors to internalizing symptoms in a national sample of adolescents during the COVID-19 pandemic -
Internalizing problems are common in adolescence and increased substantially during the COVID-19 pandemic. Leveraging data from a U.S. nationally diverse sample of 2,954 adolescents (ages 13-16), we examined the associations between factors at multiple levels of youths’ ecologies – spanning indicators of threat and deprivation – and their depression and anxiety symptoms during the COVID-19 pandemic. Furthermore, we examined how these associations differed by adolescents’ racial/ethnic groups. Consistent with socio-ecological models, we found that indicators of threat and deprivation at the adolescents’ immediate home, and more distal neighborhood environments were associated with their depression and anxiety symptoms. The patterns of associations were similar across racial/ethnic groups in multigroup structural equation models. Additionally, we found that mean levels of internalizing symptoms and socio-ecological predictors significantly differed across racial/ethnic groups. These findings have important implications for understanding multi-level contributors to mental health among adolescents which may inform research, practice, and policy.
- SARS-CoV-2-specific T cells in unexposed adults display broad trafficking potential and cross-react with commensal antigens -
The baseline composition of T cells directly impacts later response to a pathogen, but the complexity of precursor states remains poorly defined. Here we examined the baseline state of SARS-CoV-2 specific T cells in unexposed individuals. SARS-CoV-2 specific CD4+ T cells were identified in pre-pandemic blood samples by class II peptide-MHC tetramer staining and enrichment. Our data revealed a substantial number of SARS-CoV-2 specific T cells that expressed memory phenotype markers, including memory cells with gut homing receptors. T cell clones generated from tetramer- labeled cells cross-reacted with bacterial peptides and responded to stool lysates in a MHC-dependent manner. Integrated phenotypic analyses revealed additional precursor diversity that included T cells with distinct polarized states and trafficking potential to other barrier tissues. Our findings illustrate a complex pre-existing memory pool poised for immunologic challenges and implicate non-infectious stimuli from commensal colonization as a factor that shapes pre- existing immunity.
- Th1, Th2 and Th17 inflammatory pathways synergistically correlate with cardiometabolic processes. A case study in COVID-19. -
A predominant source of complication in SARS-CoV-2 patients arises from the cytokine storm, an elevated expression of inflammatory helper T-cell associated cytokines that can lead to tissue damage and organ failure. The high inflammatory burden of this viral infection often results in cardiovascular comorbidities. A better understanding of the interaction between the cytokine storm and cardiovascular proteins might inform medical decisions and therapeutic approaches. We hypothesized that all major helper T-cell inflammatory pathways (Th1, Th2 and Th17) synergistically contribute to cardiometabolic modifications in serum of COVID-19 patients. We proved our hypothesis by integrating Th1, Th2 and Th17 cytokines to predict expression of cardiometabolic proteins profiled by OLINK proteomics.
- Peptide-antibody Fusions Engineered by Phage Display Exhibit Ultrapotent and Broad Neutralization of SARS-CoV-2 Variants -
The COVID-19 pandemic has been exacerbated by the emergence of variants of concern (VoCs). Many VoC mutations are found in the viral spike protein (S-protein), and are thus implicated in host infection and response to therapeutics. Bivalent neutralizing antibodies (nAbs) targeting the S-protein receptor-binding domain (RBD) are promising therapeutics for COVID-19, but are limited due to low potency and vulnerability to RBD mutations found in VoCs. To address these issues, we used naive phage-displayed peptide libraries to isolate and optimize 16-residue peptides that bind to the RBD or the N-terminal domain (NTD) of the S-protein. We fused these peptides to the N-terminus of a moderate affinity nAb to generate tetravalent peptide-IgG fusions, and showed that both classes of peptides were able to improve affinities for the S-protein trimer by >100-fold (apparent KD <1 pM). Critically, cell-based infection assays with a panel of six SARS-CoV-2 variants demonstrate that an RBD-binding peptide was able to enhance the neutralization potency of a high-affinity nAb >100-fold. Moreover, this peptide-IgG was able to neutralize variants that were resistant to the same nAb in the bivalent IgG format. To show that this approach is general, we fused the same peptide to a clinically approved nAb drug, and showed that it rescued neutralization against a resistant variant. Taken together, these results establish minimal peptide fusions as a modular means to greatly enhance affinities, potencies, and breadth of coverage of nAbs as therapeutics for SARS-CoV-2.
- SARS-CoV-2 Virus like Particles produced by a single recombinant baculovirus generate potent neutralizing antibody that protects against variant challenge -
The Covid-19 pandemic caused by SARS-CoV-2 infection has highlighted the need for the rapid generation of efficient vaccines for emerging disease. Virus-like particles, VLPs, are an established vaccine technology that produces virus- like mimics, based on expression of the structural proteins of a target virus that can stimulate strong neutralizing antibody responses. SARS-CoV-2 is a coronavirus where the basis of VLP formation has been shown to be the co-expression of the spike, membrane and envelope structural proteins. Here we describe the generation of SARS-CoV-2 VLPs by the co expression of the salient structural proteins in insect cells using the established baculovirus expression system. VLPs were heterologous ~100nm diameter enveloped particles with a distinct fringe that reacted strongly with SARS-CoV-2 convalescent sera. In a Syrian hamster challenge model, a non adjuvanted VLPs induced neutralizing antibodies to the VLP-associated Wuhan S protein, reduced virus shedding following a virulent challenge with SARS-CoV-2 (B.1.1.7 variant) and protected against disease associated weight loss. Immunized animals showed reduced lung pathology and lower challenge virus replication than the non-immunized controls. Our data, using an established and scalable technology, suggest SARS-CoV-2 VLPs offer an efficient vaccine that mitigates against virus load and prevents severe disease.
- A human monoclonal antibody potently pan-neutralizes SARS-CoV-2 VOCs by targeting RBD invariant sites -
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of SARS- CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS- CoV-2 vaccine.
- Heterologous Vaccination with SARS-CoV-2 Spike saRNA Prime followed by DNA Dual-Antigen Boost Induces Robust Antibody and T-Cell Immunogenicity against both Wild Type and Delta Spike as well as Nucleocapsid Antigens -
We assessed if immune responses are enhanced in CD-1 mice by heterologous vaccination with two different nucleic acid-based COVID-19 vaccines: a next-generation human adenovirus serotype 5 (hAd5)-vectored dual-antigen spike (S) and nucleocapsid (N) vaccine (AdS+N) and a self-amplifying and -adjuvanted S RNA vaccine (SASA S) delivered by a nanostructured lipid carrier. The AdS+N vaccine encodes S modified with a fusion motif to increase cell-surface expression. The N antigen is modified with an Enhanced T-cell Stimulation Domain (N-ETSD) to direct N to the endosomal/lysosomal compartment to increase the potential for MHC class I and II stimulation. The S sequence in the SASA S vaccine comprises the D614G mutation, two prolines to stabilize S in the prefusion conformation, and 3 glutamines in the furin cleavage region to increase cross-reactivity across variants. CD-1 mice received vaccination by prime > boost homologous and heterologous combinations. Humoral responses to S were the highest with any regimen including the SASA S vaccine, and IgG against wild type S1 and Delta (B.1.617.2) variant S1 was generated at similar levels. An AdS+N boost of an SASA S prime enhanced both CD4+ and CD8+ T-cell responses to both S wild type and S Delta peptides relative to all other vaccine regimens. Sera from mice receiving SASA S homologous or heterologous vaccination were found to be highly neutralizing of all pseudovirus tested: Wuhan, Delta, and Beta strain pseudoviruses. The findings here support the clinical testing of heterologous vaccination by an SASA S > AdS+N regimen to provide increased protection against COVID-19 and SARS-CoV-2 variants.
- In silico study on the effects of disulfide bonds in ORF8 of SARS-CoV-2 -
The COVID-19 epidemic, caused by virus SARS-CoV-2, has been a pandemic and threatening everyone’s health in the past two years. In SARS-CoV-2, the accessory protein ORF8 plays an important role in immune modulation. Here we present an in silico study on the effects of the disulfide bonds in ORF8, including the effects on the structures, the binding sites and free energy when ORF8 binds to the human leukocyte antigen (HLA-A). Using the explicit solvent Molecular Dynamics (MD) simulations, we collect the conformational ensembles on ORF8 with different disulfide bonds reduction schemes. With a new visualization technique on the local geometry, we analyze the effects of the disulfide bonds on the structure of ORF8. We find that the disulfide bonds have large influences on the loop regions of the surface. Moreover, by performing docking between HLA-A and the conformational ensembles of ORF8, we predict the preferred binding sites and find that most of them are little affected by the disulfide bonds. Further, we estimate the binding free energy between HLA-A and ORF8 with different disulfide bonds reductions. In the end, from the comparison with the available experimental results on the epitopes of ORF8, we validated our binding sites prediction. All the above observations may provide inspirations on inhibitor/drug design against ORF8 based on the binding pathway with HLA-A.
- Protective immunity of the primary SARS-CoV-2 infection reduces disease severity post re-infection with Delta variants in Syrian hamsters -
Delta variant has evolved to become dominant SARS-CoV-2 lineage worldwide and there are reports of secondary infections with varying severity in vaccinated and unvaccinated naturally recovered COVID-19 patients. As the protective immunity following the infection wanes within few months, studies of re-infection after prolonged duration is needed. Hence we assessed the potential of re-infection by Delta, Delta AY.1 and B.1 in COVID-19 recovered hamsters after 3 months of infection. Re-infection with Delta and B.1 variants in hamsters showed reduced viral shedding, lung pathology and lung viral load, whereas the upper respiratory tract viral load remained similar to that of first infection. The reduction in viral load and lung pathology after re-infection with Delta AY.1 variant was not marked. Further we assessed the disease characteristics of Delta AY.1 to understand whether it has any replication advantage over Delta variant and B.1 variant, an early isolate in Syrian hamsters. Body weight changes, viral load in respiratory organs, lung pathology, cytokine response and neutralizing antibody response were assessed. Delta AY.1 variant produced milder disease in comparison to Delta variant and the neutralizing response was similar against Delta, B.1 and B.1.351 variant in contrast to Delta or B.1 infected hamsters which showed a significant reduction in neutralization titres against B.1.351. Elevation of IL-6 levels was observed post infection in hamsters after primary infection. The prior infection could not produce sterilizing immunity but the protective effect was evident following re-infection. This indicates the importance of the transmission prevention efforts even after achieving herd immunity.
- A large-scale systematic survey of SARS-CoV-2 antibodies reveals recurring molecular features -
In the past two years, the global research in combating COVID-19 pandemic has led to isolation and characterization of numerous human antibodies to the SARS-CoV-2 spike. This enormous collection of antibodies provides an unprecedented opportunity to study the antibody response to a single antigen. Using information derived from 88 research publications and 13 patents, we have assembled a dataset of ~8,000 human antibodies to the SARS-CoV-2 spike from >200 donors. Analysis of antibodies that target different domains of the spike protein reveals a number of common (public) responses to SARS-CoV-2, exemplified via recurring IGHV/IGK(L)V pairs, CDR H3 sequences, IGHD usage, and somatic hypermutation. We further present a proof-of-concept for predicting antigen specificity by using deep learning to differentiate sequences of antibodies to SARS-CoV-2 spike and to influenza hemagglutinin. Overall, this study not only provides an informative resource for antibody research, but fundamentally advances our molecular understanding of public antibody responses.
- Main protease mutants of SARS-CoV-2 variants remain susceptible to PF-07321332 -
The COVID-19 pandemic continues to be a public health threat. Multiple mutations in the spike protein of emerging variants of SARS-CoV-2 appear to impact on the effectiveness of available vaccines. Specific antiviral agents are keenly anticipated but their efficacy may also be compromised in emerging variants. One of the most attractive coronaviral drug targets is the main protease (Mpro). A promising Mpro inhibitor of clinical relevance is the peptidomimetic PF-07321332. We expressed Mpro of five SARS-CoV-2 lineages (C.37 Lambda, B.1.1.318, B.1.2, B.1.351 Beta, P.2 Zeta), each of which carries a strongly prevalent missense mutation (G15S, T21I, L89F, K90R, L205V). Enzyme kinetics showed that these Mpro variants are similarly catalytically competent as the wildtype. We show that PF-07321332 has similar potency against the variants as against the wildtype. Our in vitro data suggest that the efficacy of specific Mpro inhibitors such as PF-07321332 is not compromised in current COVID-19 variants.
- sgDI-tector: defective interfering viral genome bioinformatics for detection of coronavirus subgenomic RNAs -
Coronavirus RNA-dependent RNA polymerases produce subgenomic RNAs (sgRNAs) that encode viral structural and accessory proteins. User-friendly bioinformatic tools to detect and quantify sgRNA production are urgently needed to study the growing number of next-generation sequencing (NGS) data of SARS-CoV-2. We introduced sgDI-tector to identify and quantify sgRNA in SARS-CoV-2 NGS data. sgDI-tector allowed detection of sgRNA without initial knowledge of the transcription-regulatory sequences. We produced NGS data and successfully detected the nested set of sgRNAs with the ranking M>ORF3a>N>ORF6>ORF7a>ORF8>S>E>ORF7b. We also compared the level of sgRNA production with other types of viral RNA products such as defective interfering viral genomes.
- Case Study of High-Throughput Drug Screening and Remote Data Collection for SARS-CoV-2 Main Protease by Using Serial Femtosecond X-ray Crystallography -
Since early 2020, COVID-19 has grown to affect the lives of billions globally. A worldwide investigation has been ongoing for characterizing the virus and also for finding an effective drug and developing vaccines. As time has been of the essence, a crucial part of this research has been drug repurposing; therefore, confirmation of in-silico drug screening studies have been carried out for this purpose. Here we demonstrated the possibility of screening a variety of drugs efficiently by leveraging a high data collection rate of 120 images/second with the new low-noise, high dynamic range ePix10k2M Pixel Array Detector installed at the Macromolecular Femtosecond Crystallography (MFX) instrument at the Linac Coherent Light Source (LCLS). The X-ray Free-Electron Laser (XFEL) is used for remote high-throughput data collection for drug repurposing of the main protease (Mpro) of SARS-CoV-2 at ambient temperature with mitigated X-ray radiation damage. We obtained multiple high-resolution structures soaked with 9 drug candidate molecules in two crystal forms. Although our drug binding attempts failed, we successfully established a high-throughput Serial Femtosecond X-ray crystallographic (SFX) data collection protocol.
- A recombinant SARS-CoV-2 RBD antigen expressed in insect cells elicits immunogenicity and confirms safety in animal models -
COVID-19 pandemic has accelerated the development of vaccines against its etiologic agent, SARS-CoV-2. However, the emergence of new variants of the virus requires new immunization strategies in addition to the current vaccines approved for human administration. In the present report, the immunological and safety evaluation in mice and hamsters of a subunit vaccine based on the RBD sub-domain with two adjuvants of oil origin is described. The RBD protein was expressed in insect cells and purified by chromatography until >95% purity. The protein was shown to have the appropriate folding as determined by ELISA and flow cytometry binding assays to its receptor, as well as by its detection by hamster immune anti-S1 sera under non-reducing conditions. In immunization assays in mice and hamsters, the purified RBD formulated with adjuvants based on oil-water emulsifications and squalene was able to stimulate specific neutralizing antibodies and confirm the secretion of IFN-{gamma} after stimulating spleen cells with the purified RBD. The vaccine candidate was shown to be safe, as demonstrated by the histopathological analysis in lungs, liver and kidney. These results demonstrate the potential of the purified RBD administered with adjuvants through an intramuscular route, to be evaluated in a challenge against SARS-CoV-2 and determine its ability to confer protection against infection.
- Myeloid cell-driven nonregenerative pulmonary scarring is conserved in multiple nonhuman primate species regardless of SARS-CoV-2 infection modality -
The novel coronavirus SARS-CoV-2 has caused a worldwide pandemic resulting in widespread efforts in development of animal models that recapitulate human disease for evaluation of medical countermeasures, and to dissect COVID-19 immunopathogenesis. We tested whether route of experimental infection substantially changes COVID-19 disease characteristics in two species (Macaca mulatta; rhesus macaques; RM, Chlorocebus atheiops; African green monkeys; AGM) of nonhuman primates. Species-specific cohorts of RM and AGM Rhesus macaques (Macaca mulatta, RMs) and African green monkeys (Chlorocebus aethiops, AGMs) were experimentally infected with homologous SARS-CoV-2 by either direct mucosal instillation or small particle aerosol in route-discrete subcohorts. Both species demonstrated equivalent infection initially by either exposure route although the magnitude and duration of viral loading was greater in AGMs than that of the RM. Clinical onset was nearly immediate (+1dpi) in mucosally-exposed cohorts whereas aerosol-infected animals began to show signs +7dpi. Myeloid cell responses indicative of the development of pulmonary scarring and extended lack of regenerative capacity in the pulmonary compartment was a conserved pathologic response in both species by either exposure modality. This pathological commonality may be useful in future anti-fibrosis therapeutic evaluations and expands our understanding of how SARS-CoV-2 infection leads to ARDS and functional lung damage.
Study to Evaluate the Effects of RO7496998 (AT-527) in Non-Hospitalized Adult and Adolescent Participants With Mild or Moderate COVID-19 - Condition: COVID-19
Interventions: Drug: RO7496998; Drug: Placebo
Sponsor:
Hoffmann-La Roche
Suspended
Allogenic UCMSCs as Adjuvant Therapy for Severe COVID-19 Patients - Condition: Covid 19
Interventions: Biological: Normoxic Allogenic UCMSC; Other: Normal saline solution
Sponsors: Kementerian Riset dan Teknologi / Badan Riset dan Inovasi Nasional, Indonesia; Dr. Moewardi General Hospital, Surakarta, Indonesia; Dr. Sardjito General Hospital, Yogyakarta, Indonesia; Dr. Hasan Sadikin General Hospital, Bandung, Indonesia; PT Bifarma Adiluhung
Recruiting
Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for Mild-to-Moderate COVID-19: A Phase II Clinical Trial - Condition: COVID-19
Intervention: Drug: ExoFlo
Sponsor: Direct Biologics, LLC
Recruiting
Physical Fitness in Young Healthy Adults After COVID-19 Infection - Condition: COVID-19
Interventions: Other: Physical Activity Level; Other: Evaluation of knee extension and elbow flexion muscle strength; Other: Evaluation of functional strength of trunk muscles; Other: Muscle Endurance; Other: Flexibility; Other: Balance; Other: Fatigue
Sponsor:
Baskent University
Enrolling by invitation
The South Proxa-Rescue AndroCoV Trial Against COVID-19 - Condition: COVID-19
Interventions: Drug: Proxalutamide; Drug: Placebo
Sponsors: Corpometria Institute; Hospital da Brigada Militar de Porto Alegre, Porto Alegre, Brazil; Hospital Arcanjo Sao Miguel, Gramado, Brazil; Hospital Unimed Chapeco, Chapeco, Brazil
Completed
Vitamin D Supplementation and Clinical Improvement in COVID-19 - Condition: COVID-19
Interventions: Dietary Supplement: Vitamin D3 10000 IU; Dietary Supplement: Vitamin D3 1000 IU
Sponsor: Bumi Herman
Completed
Partnerships to Address COVID-19 Inequities - Condition: COVID-19
Interventions: Behavioral: Crowdsourced campaign package; Behavioral: Standard information
Sponsor: Duke University
Not yet recruiting
Study to Evaluate the inHaled Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) On the Protective-Efficacy in Adults (SeiHOPE) - Condition: COVID-19
Interventions: Biological: Recombinant COVID-19 vaccine (adenovirus type 5 vector) for Inhalation (Ad5-nCoV-IH); Biological: Placebo
Sponsors: CanSino Biologics Inc.; Beijing Institute of Biotechnology
Not yet recruiting
Pharmacokinetics, Pharmacodynamics, and Safety of Single-dose Sotrovimab in High-risk Pediatric Participants With Mild to Moderate COVID-19 - Condition: COVID-19
Intervention: Biological: Sotrovimab
Sponsors:
GlaxoSmithKline; Vir Biotechnology, Inc.
Not yet recruiting
Inhaled Recombinant Non-immunogenic Staphylokinase vs Placebo in Patients With COVID-19 - FORRIF Trial - Condition: COVID-19
Interventions: Drug: Recombinant nonimmunogenic staphylokinase; Drug: Placebo
Sponsors: Supergene, LLC; Russian Academy of Medical Sciences
Not yet recruiting
Safety and Immunogenicity of COVID-19 Vaccine, Inactivated in Healthy Population Aged From 3 to 11 Years - Condition: COVID-19
Intervention: Biological: COVID-19 Vaccine,Inactivated
Sponsor: Sinovac Biotech Co., Ltd
Not yet recruiting
Nutritional Supplementation of Vitamin D, Quercetin and Curcumin With Standard of Care for Managing Mild Early Symptoms of COVID-19 - Condition: COVID-19
Interventions: Drug: Standard of care; Dietary Supplement: Investigational treatment
Sponsor: King Edward Medical University
Recruiting
Anti-COVID19 VaccinaTion AKS-452 BOOSTER (ACT-BOOSTER Study) - Conditions: COVID-19; Booster Vaccine
Intervention: Biological: AKS-452X
Sponsors: University Medical Center Groningen; Akston Biosciences Corp; TRACER Europe BV; PRA Health Sciences
Not yet recruiting
Clinical Study for Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) Booster Immunization - Condition: COVID-19 Pandemic
Intervention: Biological: Recombinant SARS-CoV-2 Fusion Protein Vaccine
Sponsor: Livzon Pharmaceutical Group Inc.
Active, not recruiting
The Immune Response of Heterologous Boost Third Dose of mRNA and Protein COVID-19 Vaccine: a Single-blind, and Randomized Study - Conditions: COVID-19; Breakthrough Infection
Interventions: Biological: BNT162b2; Biological: mRNA-1273; Biological: MCV COVID-19 vaccine
Sponsors: Chang Gung Memorial Hospital; Medigen Vaccine Biologics Corp.
Not yet recruiting
A hydrated 2,3-diaminophenazinium chloride as a promising building block against SARS-CoV-2 - Phenazine scaffolds are the versatile secondary metabolites of bacterial origin. It functions in the biological control of plant pathogens and contributes to the producing strains ecological fitness and pathogenicity. In the light of the excellent therapeutic properties of phenazine, we have synthesized a hydrated 2,3-diaminophenazinium chloride (DAPH(+)Cl(-)·3H(2)O) through direct catalytic oxidation of o-phenylenediamine with an iron(III) complex, [Fe(1,10-phenanthroline)(2)Cl(2)]NO(3) in…
Chemical constituents and biological activities of Artemisia argyi H.Lév. & vaniot - Artemisia argyi is a widely distributed and inexpensive plant resource, and study on its chemical compositions and biological activities will provide an important basis for its food applications and pharmaceutical developments. In this study, fourteen known guaiane-type sesquiterpenes (1-14), four known eudesmane-type sesquiterpenes (15-18), two known germacranolide-type sesquiterpenes (19, 20), and eight other types of terpenoids (20-28) were isolated from the leaves of A. argyi by polyamide…
In Vitro Metabolism, Pharmacokinetics and Drug Interaction Potentials of Emvododstat, a DHODH Inhibitor - Emvododstat was identified as a potent inhibitor of dihydroorotate dehydrogenase and is now in clinical development for the treatment of acute myeloid leukaemia and COVID-19. The objective of this paper is to evaluate the metabolism, pharmacokinetics, and drug interaction potentials of emvododstat.Emvododstat showed high binding to plasma protein with minimal distribution into blood cells in mouse, rat, dog, monkey, and human whole blood.O-Demethylation followed by glucuronidation appeared to be…
Comparison of Antibody Response Elicited by ChAdOx1 and BNT162b2 COVID-19 Vaccine - CONCLUSION: Both the ChAdOx1- and BNT162b2-vaccinated groups showed high seropositivity for anti-S and neutralizing antibodies. The SIR of neutralizing antibodies in the ChAdOx1 vaccine group was higher in women than in men. Enhanced antibody responses were observed in participants vaccinated with BNT162b2 compared to those vaccinated with the ChAdOx1 vaccine.
Self-assembling short immunostimulatory duplex RNAs with broad spectrum antiviral activity - The current COVID-19 pandemic highlights the need for broad-spectrum antiviral therapeutics. Here we describe a new class of self-assembling immunostimulatory short duplex RNAs that potently induce production of type I and type III interferon (IFN-I and IFN-III), in a wide range of human cell types. These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique conserved sequence motif (sense strand:…
Genome-wide characterization of SARS-CoV-2 cytopathogenic proteins in the search of antiviral targets - Therapeutic inhibition of critical viral functions is important for curtailing coronavirus disease-2019 (COVID-19). We sought to identify antiviral targets through genome-wide characterization of SARS-CoV-2 proteins that are crucial for viral pathogenesis and that cause harmful cytopathic effects. All twenty-nine viral proteins were tested in a fission yeast cell-based system using inducible gene expression. Twelve proteins including eight non-structural proteins (NSP1, NSP3, NSP4, NSP5, NSP6,…
LRRC15 is an inhibitory receptor blocking SARS-CoV-2 spike-mediated entry in trans - SARS-CoV-2 infection is mediated by the entry receptor ACE2. Although attachment factors and co-receptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surface ome CRISPR activation screen, we identified human LRRC15 as an inhibitory receptor for SARS-CoV-2 entry. LRRC15 directly binds to the receptor-binding domain (RBD) of spike protein with a moderate affinity and inhibits spike-mediated entry. Analysis of human lung…
SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy - The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) has caused severe morbidity and mortality in humans. It is urgent to understand the function of viral genes. However, the function of open reading frame 10 (ORF10), which is uniquely expressed by SARS-CoV-2, remains unclear. In this study, we showed that overexpression of ORF10 markedly suppressed the expression of type I interferon (IFN-I) genes and IFN-stimulated…
Identification of oligosaccharyltransferase as a host target for inhibition of SARS-CoV-2 and its variants - No abstract
Dysregulation of ACE (Angiotensin-Converting Enzyme)-2 and Renin-Angiotensin Peptides in SARS-CoV-2 Mediated Mortality and End-Organ Injuries - ACE (angiotensin-converting enzyme)-2 as the target for SARS-CoV-2 also negatively regulates the renin-angiotensin system. Pathological activation of ADAM17 (A disintegrin and metalloproteinase-17) may potentiate inflammation and diminish ACE2-mediated tissue protection through proteolytic shedding, contributing to SARS-CoV-2 pathogenesis. We aim to examine plasma soluble ACE2 and angiotensin profiles in relation to outcomes by enrolling consecutive patients admitted for COVID-19 with baseline…
Murine monoclonal antibodies against RBD of the SARS-CoV-2 spike protein as useful analytical tools for subunit vaccine development and clinical trials - COVID-19 pandemic poses a serious threat to human health; it has completely disrupted global stability, making vaccine development an important goal to achieve. Monoclonal antibodies play an important role in subunit vaccines strategies. In this work, nine murine MAbs against the RBD of the SARS-CoV-2 spike protein were obtained by hybridoma technology. Characterization of purified antibodies demonstrated that five of them have affinities in the order of 10⁸ L/mol. Six of the eight MAbs showed…
Structural and theoretical investigations, Hirshfeld surface analysis and anti-SARS CoV-2 of nickel (II) coordination complex - A nickel(II) Schiff base complex, Ni(L)(DMF), was synthesized by treating NiCl(2).6H(2)O with an ONS-donor Schiff base ligand(H(2)L) derived from the condensation 3,5-Dichlorosalicylaldehyde and 4,4-Dimethyl-3-thiosemicarbazide in DMF. The geometry around the center metal ion in Ni(L)(DMF) was square planar as revealed by the data collection from diffraction studies. DFT calculations were performed on the complex to get a structure-property relationship. Hirshfeld surface analysis was…
Mechanistic Insights into SARS-CoV-2 Main Protease Inhibition Reveals Hotspot Residues - The main protease (M^(pro)) is a key enzyme responsible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication that causes the spread of the global pandemic novel coronavirus (nCOVID-19) infection. In the present study, multiple computational approaches such as docking, long-range molecular dynamics (MD) simulations, and binding free-energy (BFE) estimation techniques were employed to investigate the mechanistic basis of the high-affinity inhibitors─GC-376, Calpain XII, and…
Survey on usage and concerns of a COVID-19 contact tracing application in Japan - CONCLUSIONS: The findings suggest that income may create inequalities in the efficacy and effectiveness of COVID-19 contact tracing applications. Awareness activity strategies to dispel such concerns and support low-income individuals may be needed.
Kant on Remote Working: a Moral Defence - In this article I maintain that when employers could free workers from the space constraint of the office without incurring unbearable economic losses, it is morally wrong not to grant workers the possibility to work remotely, as this violates the humanity formulation of Kant’s categorical imperative. The article therefore aims to contribute to the development of Kantian business ethics, taking into account a series of empirical evidence gathered in the wake of the Covid-19 pandemic. I firstly…
P2P 네트워크를 이용한 내장된 화상회의 시스템 - 본 발명은 P2P 네트워크를 이용한 내장된 화상회의 시스템에 관한 것으로, 상태표시부(1), 영상송출부(2), 제어부(3), 광고부(4), 입력부(5)를 포함한다. - link
A DOORBELL SYSTEM FOR MONITORING AND RECORDING A PHYSIOLOGICAL DATA OF A PERSON - AbstractTitle: A doorbell system for monitoring and recording a physiological data of a person The present invention provides a doorbell system 500 for monitoring and recording a physiological data of a person. The doorbell system 500 having a transmitter module 100 and a receiving module 200. The transmitter module 100 is having a TOF sensor module 110, an ultrasound detector 120, and an infrared detector 130. Further, a speech recognition system 150, a facial recognition system 160, and a temperature detector 190 are provided for recognizing speech, face, and temperature of the person by comparing pre-stored data. A controlling module 180 is set with a predefined commands for communicating with the transmitter module 100 and receiving module 200. The collected facial and speech data is compared and matched with the pre-stored data then the temperature detector 190 triggers and the door opens when the captured body temperature of the person is matched within the predefined range of temperature.Figure 1 - link
A study of contemporary trends in investing patterns, household savings, and economic investment. - Because household savings and household investments are intertwined and interdependent, they are discussed briefly in this paper. Household savings account for more than half of a country’s capital formation, which fluctuates due to a variety of economic factors such as inflation and interest rates. Households should gradually shift their savings and investments from physical assets to financial assets to avoid a sudden change in wealth. They should also save and invest using a variety of platforms. Trends in investing and saving will be easier to track and measure this way. This year’s domestic saving rate in India is 2.3 percent lower than last year’s and 1.2 percent lower than the year before. Since 2011, general domestic savings have been steadily declining, with the trend continuing into the following year. According to official data, the GDP in 2020 shrank by 23.9%, the least in previous years and the least since the Covid-19 pandemic in previous years. As a result, the information presented in this paper is drawn from and evaluated from other sources - link
PROLIPOSOMAL DRY POWDER INHALER OF REMDESIVIR - The present invention is related to Proliposomal Dry Powder Inhaler of Remdesivir and its method thereof for the treatment of viral infections such Coronaviridae (including COVID-19 infection). - link
Use of Diminazene Aceturate, Xanthenone, ACE 2 activators or analogs for the Treatment and therapeutic use of COVID-19 on human patients. - - link
ACTIVE RIDER SAFETY SYSTEM FOR TWO WHEELERS - The present invention relates to an active rider safety system for two wheelers comprising, a protective case equipped by a user for riding, where the case is integrated with multiple piezoelectric sensor that determines fastening of the case by user, a processing unit linked to the sensor, where the unit detects absence of case upon fetching data from the sensor below a threshold value and thereby terminates operation of ignition by stopping a coupled motor operated via a radio frequency module, an alcohol detection sensor that detects presence of alcohol and send data to processing unit, a temperature sensor that measures temperature of the user, an accelerometer sensor that activates upon ignition us tuned on to determine presence of a crash and a navigation module that via communication module sends location of user to pre saved users and concerned authorities. - link
Anti-SARS-CoV-2 antibodies and uses thereof I - - link
Anti-SARS-CoV-2 antibodies and uses thereof II - - link
Secured Health monitoring system using cloud computing - As used in public health surveillance, the invention generally relates to remote health monitoring systems with cloud computing. This is particularly relevant about a multi-user remote health monitoring system that can detect and gather data from healthcare professionals on the ground and systems in laboratories and hospitals to help the public health sector. It is possible to utilize the system for tracking, monitoring, and collecting patient data and for querying and collecting more information on the health of the people. - link
Bst DNA聚合酶重组突变体、其编码DNA及超快磁珠LAMP检测方法 - 本发明在野生型Bst DNA聚合酶序列上进行了Ser358Asp、Thr480Asn、Asp533Glu、Ala539Gly几个点位的突变，然后将进行点突变后的Bst DNA聚合酶的292‑305的氨基酸EGLLKVVRPDTKKV替换成DPLPDLIHPRTLRL，在突变后Bst DNA聚合酶序列的C端融合了一个DNA结合蛋白，在突变后Bst DNA聚合酶序列的N端融合了一个HP47多肽序列（SEQ ID No.17），在HP47多肽序列前面融合了一个CL7‑SUMO‑Tag，得到一种具有高活性和热稳定性的Bst DNA聚合酶重组突变体Super‑Bst（SEQ ID No.16）。Super‑Bst在热稳定性、特异性、链置换能力、延伸能力和逆转录酶活性上得到了显著地提升，能够耐受高盐和各类抑制剂，且可以通过原核表达和亲和纯化大量获得。本发明还公开了其编码DNA，以及一种超快磁珠LAMP检测方法。 - link