Covid-19 Sentry

Contents

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

From Preprints

• The Impact of OJK Regulation No. 48/POJK.03/2020 on the Quality of Credit and Risk Management of Banking Credit -
  The COVID-19 pandemic, which is spreading rapidly throughout the world, has seriously harmed many countries, including Indonesia. Many things have been detrimental due to COVID-19, one of which is the economic aspect. This pandemic made it difficult for many debtors to fulfil their credit obligations that led the government to issue a countercyclical policy to provide a stimulus to the national economy. This study aims to determine the impact of OJK Regulation No.48 of 2020 on credit quality and control of banking credit risk in Indonesia. The research method used is descriptive qualitative with a literature approach using secondary data. This OJK regulation regulates economic stimulus through credit restructuring and regulates the implementation of credit risk management in banks. The existence of this regulation can maintain the stability of banking performance by keeping the Non-Performing Loan (NPL) number below 5% and providing a reference for banks in risk management with a model that is relevant to economic conditions during the COVID-19 pandemic.
  🖺 Full Text HTML: The Impact of OJK Regulation No. 48/POJK.03/2020 on the Quality of Credit and Risk Management of Banking Credit
• Empty streets, busy Internet. A time series analysis of cybercrime and fraud trends during COVID-19 -
  There have been many warnings about the rising threat of cybercrime and fraud resulting from the COVID-19 lockdown measures and the associated increase in Internet use. However, there is still relatively little data with which to support the alerts and any changes may be nuanced. The present paper applies time series analysis methods to historical data on cybercrime and fraud reported to Action Fraud in the UK to examine whether any potential increases are beyond normal crime variability. Furthermore, the discrepancies between fraud types and individual and organisation victims are also analysed. The results show that while both total cybercrime and total fraud did increase beyond predicted levels, the changes in victimisation were not homogenous across fraud types and victims. The implications of these findings on how changes in routine activities in the UK have influenced cybercrime and fraud opportunities are discussed in relation to policy, practice and academic debate.
  🖺 Full Text HTML: Empty streets, busy Internet. A time series analysis of cybercrime and fraud trends during COVID-19
• Comparative analysis of codon usage patterns in SARS-CoV-2, its mutants and other respiratory viruses -
  The Coronavirus disease 2019 (COVID-19) outbreak caused by Severe Acute Respiratory Syndrome Coronavirus 2 virus (SARS-CoV-2) poses a worldwide human health crisis, causing respiratory illness with a high mortality rate. To investigate the factors governing codon usage bias in all the respiratory viruses, including SARS-CoV-2 isolates from different geographical locations (~62K) including two recently emerging strains from the United Kingdom (UK), i.e.,VUI202012/01 and South Africa (SA), i.e., 501.Y.V2 codon usage bias (CUBs) analysis was performed. The analysis includes RSCU analysis, GC content calculation, ENC analysis, di-nucleotide frequency and neutrality plot analysis. We were motivated to conduct the study to fulfil two primary aims: first, to identify the difference in codon usage bias amongst all SARS-CoV-2 genomes and secondly, to compare their CUBs properties with other respiratory viruses. A biased nucleotide composition was found as most of the highly preferred codons were A/U-ending in all the respiratory viruses studied here. When compared with human host, the RSCU analysis led to the identification of 11 over-represented codons and 9 under-represented codons in SARS-CoV-2 genomes. Correlation analysis of ENC and GC3s revealed that mutational pressure is the leading force determining the CUBs. The present study results yields a better understanding of codon usage preferences for SARS-CoV-2 genomes and discover the possible evolutionary determinants responsible for the biases found among the respiratory viruses, thus unveils a unique feature of the SARS-CoV-2 evolution and adaptation. To the best of our knowledge, this is the first attempt at comparative CUBs analysis on the worldwide genomes of SARS-CoV-2, including novel emerged strains and other respiratory viruses.
  🖺 Full Text HTML: Comparative analysis of codon usage patterns in SARS-CoV-2, its mutants and other respiratory viruses
• Maturation signatures of conventional dendritic cells in COVID-19 reflect direct viral sensing -
  Growing evidence suggests that conventional dendritic cells (cDCs) undergo aberrant maturation in COVID-19, and this adversely affects T cell activation. Here, we find that cDC2 subtypes show similar infection-induced gene signatures with an increasing gradient of expression of interferon-stimulated genes from mild to severe patients and a down-regulation of major histocompatibility complex class II (MHC class II) molecules and some inflammatory cytokines compared to the baseline level of healthy donors. In vitro, the direct exposure of cDC2s to the virus recapitulates the type of activation observed in vivo. Our findings provide evidence that SARS-CoV-2 can directly interact with cDC2s and, by down-regulating crucial molecules required for T cell activation, implements an efficient immune escape mechanism.
  🖺 Full Text HTML: Maturation signatures of conventional dendritic cells in COVID-19 reflect direct viral sensing
• Identification and quantification of SARS-CoV-2 leader subgenomic mRNA gene junctions in nasopharyngeal samples shows phasic transcription in animal models of COVID-19 and aberrant pattens in humans -
  Introduction: SARS-CoV-2 has a complex strategy for the transcription of viral subgenomic mRNAs (sgmRNAs), which are targets for nucleic acid diagnostics. Each of these sgRNAs has a unique 5 sequence, the leader-transcriptional regulatory sequence gene junction (leader-TRS-junction), that can be identified using sequencing. Results: High resolution sequencing has been used to investigate the biology of SARS-CoV-2 and the host response in cell culture models and from clinical samples. LeTRS, a bioinformatics tool, was developed to identify leader-TRS-junctions and be used as a proxy to quantify sgmRNAs for understanding virus biology. This was tested on published datasets and clinical samples from patients and longitudinal samples from animal models with COVID-19. Discussion: LeTRS identified known leader-TRS-junctions and identified novel species that were common across different species. The data indicated multi-phasic abundance of sgmRNAs in two different animal models, with spikes in sgmRNA abundance reflected in human samples, and therefore has implications for transmission models and nucleic acid-based diagnostics.
  🖺 Full Text HTML: Identification and quantification of SARS-CoV-2 leader subgenomic mRNA gene junctions in nasopharyngeal samples shows phasic transcription in animal models of COVID-19 and aberrant pattens in humans
• Optimizing vaccine allocation for COVID-19 vaccines: potential role of single-dose vaccination. -

  Most of the COVID-19 vaccines require two doses, at least 3 weeks apart. In the first few months of vaccine deployment, vaccine shortages will be inevitable. Current vaccine prioritization guidelines for COVID-19 vaccines all assume two-dose vaccine deployment. However, vaccinating twice as many people with a single dose of vaccine might be a better use of resources. Utilizing an age-stratified mathematical model combined with optimization algorithms, we determined the optimal vaccine allocation with one and two doses of vaccine to minimize five key metrics of disease burden (total infections, symptomatic infections, deaths, peak non-ICU and ICU hospitalizations) under a variety of assumptions (different levels of social distancing, vaccine availability, mode of action of vaccines, vaccination rate). Our results suggest that maintaining current social distancing interventions and speedy vaccine deployment are key for successful vaccination campaigns. Further, we show that the optimal allocation of vaccine critically depends on the single-dose efficacy (SDE). If the SDE is high, then under the majority of scenarios considered, single-dose vaccination is the optimal use of vaccine, preventing up to 48% more deaths than a strategy allocating vaccine to the high-risk (older age groups in our model) first. If the SDE is low or medium, then our results suggest that mixed vaccination campaigns with one and two doses of vaccine are best. Our work suggests that it is an absolute imperative to quickly and fully determine the efficacy of single-dose vaccines, as single-dose vaccinations can put an end to this pandemic much more quickly.

  🖺 Full Text HTML: Optimizing vaccine allocation for COVID-19 vaccines: potential role of single-dose vaccination.
• Altered Sub-Genomic RNA Expression in SARS-CoV-2 B.1.1.7 Infections -
  SARS-CoV-2 lineage B.1.1.7 viruses are more transmissible, may lead to greater clinical severity, and result in modest reductions in antibody neutralization. subgenomic RNA (sgRNA) is produced by discontinuous transcription of the SARS-CoV-2 genome and is a crucial step in the SARS-CoV-2 life cycle. Applying our tool (periscope) to ARTIC Network Oxford Nanopore genomic sequencing data from 4400 SARS-CoV-2 positive clinical samples, we show that normalised sgRNA expression profiles are significantly increased in B.1.1.7 infections (n=879). This increase is seen over the previous dominant circulating lineage in the UK, B.1.177 (n=943), which is independent of genomic reads, E gene cycle threshold and day of illness when sampling occurred. A noncanonical subgenomic RNA which could represent ORF9b is significantly enriched in B.1.1.7 SARS-CoV-2 infections, potentially as a result of a triple nucleotide mutation leading to amino acid substitution D3L in nucleocapsid in this lineage which increases complementarity with the genomic leader sequence. These findings provide a unique insight into the biology of B.1.1.7 and support monitoring of sgRNA profiles in sequence data to evaluate emerging potential variants of concern.
  🖺 Full Text HTML: Altered Sub-Genomic RNA Expression in SARS-CoV-2 B.1.1.7 Infections
• Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice -
  The speed at which several COVID-19 vaccines went from conception to receiving FDA and EMA approval for emergency use is an achievement unrivaled in the history of vaccine development. Mass vaccination efforts using the highly effective vaccines are currently underway to generate sufficient herd immunity and reduce transmission of the SARS-CoV-2 virus. Despite the most advanced vaccine technology, global recipient coverage, especially in resource-poor areas remains a challenge as genetic drift in naive population pockets threatens overall vaccine efficacy. In this study, we described the production of insect-cell expressed SARS-CoV-2 spike protein ectodomain and examined its immunogenicity in mice. We demonstrated that, when formulated with CoVaccine HTTM adjuvant, an oil-in-water nanoemulsion compatible with lyophilization, our vaccine candidates elicit a broad spectrum IgG response, high neutralizing antibody titers, and a robust, antigen-specific IFN-{gamma}; secreting response from immune splenocytes in outbred mice. Our findings lay the foundation for the development of a dry-thermostabilized vaccine that is deployable without refrigeration.
  🖺 Full Text HTML: Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice
• Covid-19 lockdown: Ethnic differences in childrens self-reported physical activity and the importance of leaving the home environment. A longitudinal and cross-sectional study from the Born in Bradford birth cohort study. -

  Background In England, the onset of COVID-19 and a rapidly increasing infection rate resulted in a lockdown (March-June 2020) which placed strict restrictions on movement of the public, including children. Using data collected from children living in a multi-ethnic city with high levels of deprivation, this study aimed to: (1) report childrens self-reported physical activity (PA) during the first COVID-19 UK lockdown and identify associated factors; (2) examine changes of childrens self-reported PA prior to and during the first UK lockdown. Methods This study is part of the Born in Bradford (BiB) COVID-19 Research Study. PA (amended Youth Activity Profile), sleep, sedentary behaviours, daily frequency/time/destination/activity when leaving the home, were self-reported by 949 children (9-13 years). A sub-sample (n=634) also self-reported PA (Physical Activity Questionnaire for Children) pre-pandemic (2017-February 2020). Univariate analysis assessed differences in PA between sex and ethnicity groups; multivariable logistic regression identified factors associated with childrens PA. Differences in childrens levels of being sufficiently active were examined using the McNemar test examined change in PA prior to and during the lockdown, and multivariable logistic regression to identify factors explaining change. Results During the pandemic, White British (WB) children were more sufficiently active (34.1%) compared to Pakistani Heritage children (PH) (22.8%) or Other ethnicity children (O) (22.8%). WB children reported leaving the home more frequently and for longer periods than PH and O children. Modifiable variables related to being sufficiently active were frequency, duration, type of activity, and destination away from the home environment. There was a large reduction in children being sufficiently active during the first COVID-19 lockdown (28.9%) compared to pre-pandemic (69.4%). Conclusions Promoting safe extended periods of PA everyday outdoors is important for all children, in particular for children from ethnic minority groups. Childrens PA during the first COVID-19 UK lockdown has drastically reduced from before. Policy and decision makers, and practitioners should consider the findings in order to begin to understand the impact and consequences that COVID-19 has had upon childrens PA which is a key and vital behaviour for health and development.

  🖺 Full Text HTML: Covid-19 lockdown: Ethnic differences in childrens self-reported physical activity and the importance of leaving the home environment. A longitudinal and cross-sectional study from the Born in Bradford birth cohort study.
• Blockade of SARS-CoV-2 infection in-vitro by highly potent PI3K-α/mTOR/BRD4 inhibitor -
  Pathogenic viruses like SARS-CoV-2 and HIV hijack the host molecular machinery to establish infection and survival in infected cells. This has led the scientific community to explore the molecular mechanisms by which SARS-CoV-2 infects host cells, establishes productive infection, and causes life-threatening pathophysiology. Very few targeted therapeutics for COVID-19 currently exist, such as remdesivir. Recently, a proteomic approach explored the interactions of 26 of 29 SARS-CoV-2 proteins with cellular targets in human cells and identified 67 interactions as potential targets for drug development. Two of the critical targets, the bromodomain and extra-terminal domain proteins (BETs): BRD2/BRD4 and mTOR, are inhibited by the dual inhibitory small molecule SF2523 at nanomolar potency. SF2523 is the only known mTOR PI3K-/(BRD2/BRD4) inhibitor with potential to block two orthogonal pathways necessary for SARS-CoV-2 pathogenesis in human cells. Our results demonstrate that SF2523 effectively blocks SARS-CoV-2 replication in lung bronchial epithelial cells in vitro, showing an IC50 value of 1.5 uM, comparable to IC50 value of remdesivir (1.1 uM). Further, we demonstrated that the combination of doses of SF2523 and remdesivir is highly synergistic: it allows for the reduction of doses of SF2523 and remdesivir by 25-fold and 4-fold, respectively, to achieve the same potency observed for a single inhibitor. Because SF2523 inhibits two SARS-CoV-2 driven pathogenesis mechanisms involving BRD2/BRD4 and mTOR signaling, our data suggest that SF2523 alone or in combination with remdesivir could be a novel and efficient therapeutic strategy to block SARS-CoV-2 infection and hence be beneficial in preventing severe COVID-19 disease evolution.
  🖺 Full Text HTML: Blockade of SARS-CoV-2 infection in-vitro by highly potent PI3K-α/mTOR/BRD4 inhibitor
• Neutralizing IFNL3 Autoantibodies in Severe COVID-19 Identified Using Molecular Indexing of Proteins by Self-Assembly -
  Unbiased antibody profiling can identify the targets of an immune reaction. A number of likely pathogenic autoreactive antibodies have been associated with life-threatening SARS-CoV-2 infection; yet, many additional autoantibodies likely remain unknown. Here we present Molecular Indexing of Proteins by Self Assembly (MIPSA), a technique that produces ORFeome-scale libraries of proteins covalently coupled to uniquely identifying DNA barcodes for analysis by sequencing. We used MIPSA to profile circulating autoantibodies from 55 patients with severe COVID-19 against 11,076 DNA-barcoded proteins of the human ORFeome library. MIPSA identified previously known autoreactivities, and also detected undescribed neutralizing interferon lambda 3 (IFNL3) autoantibodies. At-risk individuals with anti-IFNL3 antibodies may benefit from interferon supplementation therapies, such as those currently undergoing clinical evaluation.
  🖺 Full Text HTML: Neutralizing IFNL3 Autoantibodies in Severe COVID-19 Identified Using Molecular Indexing of Proteins by Self-Assembly
• Low-dose lung radiotherapy for COVID-19 lung disease: a pre-clinical efficacy study in a bleomycin model of pneumonitis. -
  Purpose: Low-dose whole lung radiotherapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling and mechanisms of action. Materials and methods: Female C57BL/6 mice were treated with intranasal bleomycin sulphate (7.5 or 11.25 units/kg, day 0) then exposed to whole lung radiation therapy (0.5, 1.0, 1.5 Gy or sham, day 3). Bodyweight was measured daily and lung tissue harvested for histology and flow cytometry on day 10. Computed tomography (CT) lung imaging was performed pre-radiation (day 3) and pre-endpoint (day 10). Results: Bleomycin caused pneumonitis of variable severity which correlated with weight loss. LDLR at 1.0 Gy was associated with a significant increase in the proportion of mice recovering to 98% of initial bodyweight; many of these mice exhibited less severe histopathological lung changes. Mice experiencing moderate initial weight loss were more likely to respond to LDLR than those experiencing severe initial weight loss. LDLR (1.0 Gy) significantly reduced bleomycin induced increases in interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids. Pre-radiation, bleomycin treated mice exhibited significantly higher percentages of non-aerated lung in left than right lungs; LDLR (1.0 Gy) prevented further reductions in aerated lung volume in right but not left lungs. LDLR doses of 0.5 and 1.5 Gy did not modulate bodyweight or flow cytometric readouts of bleomycin pneumonitis. Conclusions: Our data support the concept that LDLR can ameliorate acute inflammatory lung injury, identify 1.0 Gy as the most effective dose and provide preliminary evidence that it is more effective in the context of moderate than severe pneumonitis. Mechanistically, LDLR significantly suppressed bleomycin induced accumulation of interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids in the lung.
  🖺 Full Text HTML: Low-dose lung radiotherapy for COVID-19 lung disease: a pre-clinical efficacy study in a bleomycin model of pneumonitis.
• A pharmacophore model for SARS-CoV-2 3CLpro small molecule inhibitors and in vitro experimental validation of computationally screened inhibitors -
  Among the biomedical efforts in response to the current coronavirus (COVID-19) pandemic, pharmacological strategies to reduce viral load in patients with severe forms of the disease are being studied intensively. One of the main drug target proteins proposed so far is the SARS-CoV-2 viral protease 3CLpro (also called Mpro), an essential component for viral replication. Ongoing ligand- and receptor-based computational screening efforts would be facilitated by an improved understanding of the electrostatic, hydrophobic and steric features that characterize small molecule inhibitors binding stably to 3CLpro, as well as by an extended collection of known binders. Here, we present combined virtual screening, molecular dynamics simulation, machine learning and in vitro experimental validation analyses which have led to the identification of small molecule inhibitors of 3CLpro with micromolar activity, and to a pharmacophore model that describes functional chemical groups associated with the molecular recognition of ligands by the 3CLpro binding pocket. Experimentally validated inhibitors using a ligand activity assay include natural compounds with available prior knowledge on safety and bioavailability properties, such as the natural compound rottlerin (IC50 = 37 mcM), and synthetic compounds previously not characterized (e.g. compound CID 46897844, IC50 = 31 mcM). In combination with the developed pharmacophore model, these and other confirmed 3CLpro inhibitors may provide a basis for further similarity-based screening in independent compound databases and structural design optimization efforts, to identify 3CLpro ligands with improved potency and selectivity. Overall, this study suggests that the integration of virtual screening, molecular dynamics simulations and machine learning can facilitate 3CLpro-targeted small molecule screening investigations. Different receptor-, ligand- and machine learning-based screening strategies provided complementary information, helping to increase the number and diversity of identified active compounds. Finally, the resulting pharmacophore model and experimentally validated small molecule inhibitors for 3CLpro provide resources to support follow-up computational screening efforts for this drug target.
  🖺 Full Text HTML: A pharmacophore model for SARS-CoV-2 3CLpro small molecule inhibitors and in vitro experimental validation of computationally screened inhibitors
• Optimal, near-optimal, and robust epidemic control -
  The COVID-19 pandemic has highlighted the need for control measures that reduce the epidemic peak (“flattening the curve”). Here we derive the optimal time-limited intervention for reducing peak epidemic prevalence in the standard Susceptible-Infectious-Recovered (SIR) model. We show that alternative, more practical interventions can perform nearly as well as the provably optimal strategy. However, none of these strategies are robust to implementation errors: mistiming the start of the intervention by even a single week can be enormously costly, for realistic epidemic parameters. Sustained control measures, though less efficient than optimal and near-optimal time-limited interventions, can be used in combination with time-limited strategies to mitigate the catastrophic risks of mistiming.
  🖺 Full Text HTML: Optimal, near-optimal, and robust epidemic control
• Impact of COVID-19 pandemic on Black, Asian and Minority Ethnic (BAME) communities: a qualitative study on the perspectives of BAME community leaders -

  Objectives: The aim of this study was to explore the perspectives of BAME community leaders in relation to - the impact of the COVID-19 pandemic on their communities; and BAME community perceptions, understanding and adherence to Government guidelines on COVID-19 public health measures. Design: A phenomenological approach was adopted using qualitative semi-structured interviews. Settings: Community organisations and places of worships in the West Midlands region of England. Participants: Community leaders were recruited through organisations representing BAME communities and religious places of worship. Results: A total of 19 participants took part. Participants alluded to historical and structural differences for the observed disparities in COVID-19 morbidity and mortality. Many struggled with lockdown measures which impeded cultural and religious gatherings that were deemed to be integral to the community. Cultural and social practices led to many suffering on their own as discussion of mental health was still deemed a taboo within many communities. Many expressed their community reluctance to report symptoms for the fear of financial and physical health implications. They reported increase in hate crime which was deemed to be exacerbated due to perceived insensitive messaging from authority officials and historical structural biases. Access and adherence to government guidelines was an issue for many due to language and digital barriers. Reinforcement from trusted community and religious leaders encouraged adherence. Points of support such as food banks were vital in ensuring essential supplies during the pandemic. Many could not afford masks and sanitisers. Conclusion: The study highlights the perceived impact of COVID-19 pandemic on BAME communities. Government agencies and public health agencies need to integrate with the community, and community leaders to penetrate the key messages and deliver targeted yet sensitive public health advice which incorporates cultural and religious practices. Addressing route cause of disparities is imperative to mitigate current and future pandemics.

  🖺 Full Text HTML: Impact of COVID-19 pandemic on Black, Asian and Minority Ethnic (BAME) communities: a qualitative study on the perspectives of BAME community leaders

From Clinical Trials

• Study to Evaluate a Single Dose of STI-2020 (COVI-AMG™) in Hospitalized Adults With COVID-19 - Condition:   Covid19
  Interventions:   Biological: COVI-AMG;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Safety & Efficacy of Low Dose Aspirin / Ivermectin Combination Therapy for Treatment of Covid-19 Patients - Condition:   Covid19
  Intervention:   Drug: 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1)
  Sponsors:   Makerere University;   Ministry of Health, Uganda;   Mbarara University of Science and Technology;   Joint Clinical Research Center
  Not yet recruiting

• Clinical Study in the Treatment of Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Molixan;   Drug: Placebo
  Sponsor:   Pharma VAM
  Not yet recruiting

• The Safety and Efficacy of FB2001 in Healthy Subjects and Patients With COVID-19 Infection - Condition:   Covid19
  Interventions:   Drug: FB2001;   Drug: FB2001 Placebo
  Sponsor:   Frontier Biotechnologies Inc.
  Not yet recruiting

• A Safety and Efficacy Study of Human Monoclonal Antibodies, BRII-196 and BRII-198 for the Treatment of Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: BRII-196 and BRII-198;   Drug: Placebo
  Sponsor:   Brii Biosciences, Inc.
  Not yet recruiting

• Safety, Tolerability and Pharmacokinetics of Second Generation VIR-7831 Material in Non-hospitalized Participants With Mild to Moderate COVID-19 - Condition:   Covid19
  Interventions:   Biological: VIR-7831 (Gen1);   Biological: VIR-7831 (Gen2)
  Sponsors:   Vir Biotechnology, Inc.;   GlaxoSmithKline
  Recruiting

• Protecting Native Families From COVID-19 - Condition:   COVID-19
  Interventions:   Behavioral: Motivational Interviewing;   Behavioral: COVID-19 Symptom Monitoring System;   Behavioral: Motivational Interviewing and COVID-19 Symptom Monitoring System;   Other: Supportive Services
  Sponsor:   Johns Hopkins Bloomberg School of Public Health
  Not yet recruiting

• Honey and Nigella Sativa in COVID-19 Prophylaxis - Condition:   Covid19
  Interventions:   Drug: Honey;   Drug: Nigella sativa seed;   Other: Placebo
  Sponsor:   Sohaib Ashraf
  Recruiting

• DCI COVID-19 Surveillance Project - Condition:   Covid19
  Intervention:   Diagnostic Test: SARS-CoV-2 RT-PCR Assay for Detection of COVID-19 Infection
  Sponsors:   Temple University;   Dialysis Clinic, Inc.
  Recruiting

• Safety and Efficacy of Thymic Peptides in the Treatment of Hospitalized COVID-19 Patients in Honduras - Condition:   COVID-19
  Intervention:   Biological: Thymic peptides
  Sponsors:   Universidad Católica de Honduras;   Pontificia Universidad Catolica de Chile
  Recruiting

• Safety and Immunogenicity Study in Adults of AZD1222 and rAd26-S Administered as Heterologous Prime Boost Regimen for the Prevention of Coronavirus Disease 2019 (COVID-19) - Condition:   Covid19
  Interventions:   Biological: AZD1222;   Biological: rAd26-S
  Sponsors:   R-Pharm;   AstraZeneca
  Not yet recruiting

• Safety, Tolerability, and Immunogenicity of the COVID-19 Vaccine Candidate (VBI-2902a) - Condition:   Covid19
  Interventions:   Biological: VBI-2902a;   Biological: Placebo
  Sponsor:   VBI Vaccines Inc.
  Not yet recruiting

• Breathing Exercise After COVID-19 Pneumonia - Condition:   Covid19
  Interventions:   Other: Breathing exercise with the phone application;   Other: Breathing exercise
  Sponsor:   Tokat Gaziosmanpasa University
  Not yet recruiting

• Trial Efficacy of Saisei Pharma Dietary Supplements MAF Capsules, 148 mg and M Capsules, 148 mg in Hospitalized COVID-19 Patients - Condition:   Covid19
  Interventions:   Dietary Supplement: MAF capsules 148 mg;   Dietary Supplement: M capsules 148 mg;   Other: Standard of care
  Sponsor:   Saisei Pharma
  Active, not recruiting

• (CBDRA60) to Prevent or Reduce Symptoms of COVID-19 - Condition:   COVID-19
  Interventions:   Dietary Supplement: CBDRA60 supplement;   Dietary Supplement: Placebo
  Sponsors:   Anewsha Therapeutics Inc.;   University of Michigan;   Biologics Consulting
  Not yet recruiting

From PubMed

• Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Lung Diseases: Current Status and Perspectives - Extracellular vesicles (EVs) have emerged as a potential therapy for several diseases. These plasma membrane-derived fragments are released constitutively by virtually all cell types-including mesenchymal stromal cells (MSCs)-under stimulation or following cell-to-cell interaction, which leads to activation or inhibition of distinct signaling pathways. Based on their size, intracellular origin, and secretion pathway, EVs have been grouped into three main populations: exosomes, microvesicles (or…

• THE PECULIARITY OF COVID- 19 GENOME AND THE CORONAVIRUS RNA TRANSLATION PROCESS AS APOTENTIAL TARGET FOR ETIOTROPIC MEDICATIONSWITH ADENINE AND OTHER NUCLEOTIDE ANALOGUES (REVIEW) - Despite the multifaceted effects of the medicines provided for COVID-19treatment, the number of the infected and mortality of patients increases which demonstrates the insufficient effectiveness of drugs used to fight coronavirus infections in medical practice, and clearly shows the need to develop new treatment tactics.In this review article are summarized and analyzed the literature data concerning specific features of COVID 19. Particular attention is given to genetic characteristic of this…

• Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis - Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did not bind leukocyte receptors, but lowering pH with lactic acid to mimic sepsis conditions allowed…

• Evaluating the Antimicrobial Properties of Commercial Hand Sanitizers - Hand sanitizers have been developed as a convenient means to decontaminate an individual’s hands of bacterial pathogens in situations in which soap and water are not available. Yet to our knowledge, no study has compared the antibacterial efficacy of a large collection of hand sanitizers. Using zone of growth inhibition and kill curve assays, we assessed the performance of 46 commercially available hand sanitizers that were obtained from national chain big-box stores, gasoline stations,…

• Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a burst in the upper respiratory portal for high transmissibility. To determine human neutralizing antibodies (HuNAbs) for entry protection, we tested three potent HuNAbs (IC(50) range, 0.0007-0.35 μg/mL) against live SARS-CoV-2 infection in the golden Syrian hamster model. These HuNAbs inhibit SARS-CoV-2 infection by competing with human angiotensin converting enzyme-2 for binding to the viral receptor binding…

• Targeting the Main Protease of SARS-CoV-2: From the Establishment of High Throughput Screening to the Design of Tailored Inhibitors - The main protease of SARS-CoV-2 (Mpro), the causative agent of COVID-19, constitutes a significant drug target. A new fluorogenic substrate was kinetically compared to an internally quenched fluorescent peptide and shown to be ideally suitable for high throughput screening with recombinantly expressed Mpro. Two classes of protease inhibitors, azanitriles and pyridyl esters, were identified, optimized and subjected to in-depth biochemical characterization. Tailored peptides equipped with the…

• Targeting the Coronavirus Nucleocapsid Protein through GSK-3 Inhibition - The coronaviruses responsible for severe acute respiratory syndrome (SARS-CoV), COVID-19 (SARS-CoV-2), Middle East respiratory syndrome (MERS-CoV), and other coronavirus infections express a nucleocapsid protein (N) that is essential for viral replication, transcription, and virion assembly. Phosphorylation of N from SARS-CoV by glycogen synthase kinase 3 (GSK-3) is required for its function and inhibition of GSK-3 with lithium impairs N phosphorylation, viral transcription, and replication….

• The type 2 asthma mediator IL-13 inhibits SARS-CoV-2 infection of bronchial epithelium - CONCLUSIONS: IL-13 markedly reduces susceptibility of HBECs to SARS-CoV-2 infection through mechanisms that likely differ from those activated by type I interferons. Our findings may help explain reports of relatively low prevalence of asthma in patients diagnosed with COVID-19 and could lead to new strategies for reducing SARS-CoV-2 infection.

• The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation - Viral proteins localize within subcellular compartments to subvert host machinery and promote pathogenesis. To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 SARS-CoV-2 viral proteins using proximity proteomics. This identified viral proteins at specific intracellular locations, such as association of accessary proteins with intracellular membranes, and projected SARS-CoV-2 impacts on innate immune signaling, ER-Golgi transport, and protein translation. It…

• Interleukin-1 and interleukin-6 inhibition compared with standard management in patients with COVID-19 and hyperinflammation: a cohort study - BACKGROUND: Patients with severe COVID-19 develop a life-threatening hyperinflammatory response to the virus. Interleukin (IL)-1 or IL-6 inhibitors have been used to treat this patient population, but the comparative effectiveness of these different strategies remains undetermined. We aimed to compare IL-1 and IL-6 inhibition in patients admitted to hospital with COVID-19, respiratory insufficiency, and hyperinflammation.

• Antiviral and immunomodulatory activity of curcumin: A case for prophylactic therapy for COVID-19 - Coronavirus disease-19 (COVID-19), a devastating respiratory illness caused by SARS-associated coronavirus-2 (SARS-CoV-2), has already affected over 64 million people and caused 1.48 million deaths, just 12 months from the first diagnosis. COVID-19 patients develop serious complications, including severe pneumonia, acute respiratory distress syndrome (ARDS), and or multiorgan failure due to exaggerated host immune response following infection. Currently, drugs that were effective against…

• Exploring existing drugs: proposing potential compounds in the treatment of COVID-19 - The COVID-19 situation had escalated into an unprecedented global crisis in just a few weeks. On the 30^(th) of January 2020, World Health Organization officially declared the COVID-19 epidemic as a public health emergency of international concern. The confirmed cases were reported to exceed 105,856,046 globally, with the death toll of above 2,311,048, according to the dashboard from Johns Hopkins University on the 7^(th) of February, 2021, though the actual figures may be much higher. Conserved…

• In-silico nucleotide and protein analyses of S-gene region in selected zoonotic coronaviruses reveal conserved domains and evolutionary emergence with trajectory course of viral entry from SARS-CoV-2 genomic data - CONCLUSION: phylogeny of SARS-CoV-2 genomic data suggests profiling in diverse populations with and without the outbreak alongside migration history and racial background for mutation tracking and dating of viral subtype divergence which is essential for effective management of present and future zoonotic coronavirus outbreaks.

• Needleless electrospun phytochemicals encapsulated nanofibre based 3-ply biodegradable mask for combating COVID-19 pandemic - The emergence of COVID-19 pandemic has severely affected human health and world economies. According to WHO guidelines, continuous use of face mask is mandatory for personal protection for restricting the spread of bacteria and virus. Here, we report a 3-ply cotton-PLA-cotton layered biodegradable face-mask containing encapsulated phytochemicals in the inner-filtration layer. The nano-fibrous PLA filtration layer was fabricated using needleless electrospinning of PLA & phytochemical-based…

• Repurposing of Sitagliptin- Melittin Optimized Nanoformula against SARS-CoV-2: Antiviral Screening and Molecular Docking Studies - The outbreak of the COVID-19 pandemic in China has become an urgent health and economic challenge. The objective of the current work was to evaluate the efficacy of the combined complex of Sitagliptin (SIT) with melittin (MEL) against SARS-CoV-2 virus. SIT-MEL nano-conjugates were optimized by a full three-factor bi-level (2³) factorial design. In addition, SIT concentration (mM, X1), MEL concentration (mM, X2), and pH (X3) were selected as the critical factors. Particle size (nm, Y1) and zeta…

From Patent Search

• Sars-CoV-2 vaccine antigens - - link

• SARS-COV-2 BINDING PROTEINS - - link

• Compositions and methods for detecting SARS-CoV-2 spike protein - - link

• 一种3-羟基丁酰化修饰蛋白质药物及其制备方法和应用 - 本发明涉及医药技术领域，公开了一种3‑羟基丁酰化修饰蛋白质药物（例如抗体）及其制备方法和应用，特别是一种3‑羟基丁酰化修饰抗体及其制备方法和应用。发明人经过大量实验发现，3‑羟基丁酸及其类似物修饰蛋白质药物（例如抗体）后，可以显著提高蛋白质药物的热稳定性、对蛋白酶水解的抗性，降低蛋白质药物的等电点，并显著延长其在受试者体内的半衰期，进而提高其药效。修饰后所得蛋白质药物在科研和临床方面具有广阔的应用前景和较高的商业价值。 - link

• 新冠病毒重组融合蛋白、其制备方法和应用 - 本发明提供一种新冠病毒重组融合蛋白、其制备方法和应用。本发明通过对新冠病毒S和N重组融合蛋白的基因序列进行设计，选择最优的片段进行整合，再通过人源HEK293细胞系统重组表达融合蛋白，经过纯化后对融合蛋白的分子量、纯度进行检测，最后利用融合蛋白制成新冠病毒抗体胶体金检测试纸条/试剂盒。与单独使用S蛋白或N蛋白制备的胶体金检测试纸条相比，该重组融合蛋白制备的胶体金检测试纸条具有更高的灵敏度和更低的漏检率。此外，本发明提供的新冠病毒重组融合蛋白可广泛应用于不同平台技术的新冠抗体检测试剂盒开发，如胶体金、荧光免疫层析、化学发光和酶联免疫等。 - link

• 稳定的冠状病毒重组蛋白二聚体及其表达载体 - 本发明公开了稳定的冠状病毒重组蛋白二聚体及其表达载体，冠状病毒重组蛋白，由冠状病毒S蛋白S‑RBD、冠状病毒N蛋白的CTD区N‑CTD和将二者偶联的连接子构成。本发明一些实例的冠状病毒重组蛋白，可以形成并维持稳定的二聚体结构，避免单体S‑RBD降解，有利于提高冠状病毒重组蛋白的免疫原性，有望用于制备检测试剂原料、疫苗、抗体、预防或治疗性药物。本发明一些实例的冠状病毒重组蛋白二聚体，具有很好的免疫原性。在疫苗开发领域具有广阔的应用前景。本发明一些实例的表达载体，易于表达冠状病毒重组蛋白二聚体且表达量高。 - link

• SELF-CLEANING AND GERM-KILLING REVOLVING PUBLIC TOILET FOR COVID 19 - - link

• 一种新冠病毒S1蛋白的灌流生产系统及方法 - 本发明涉及细胞生物学技术领域，提供了一种新冠病毒S1蛋白的灌流生产系统及方法，包括：细胞反应器，用于培养表达S1蛋白的细胞株；灌流系统，包括过滤装置、出液管、回液管和第一循环泵，所述过滤装置的主体内设有孔径为0.1‑0.2μm的中空纤维柱，用于过滤透出液，截留细胞培养液中的S1蛋白；所述出液管的两端分别与所述细胞反应器和所述中空纤维柱的下端相连通；所述回液管的两端分别与所述细胞反应器和所述中空纤维柱的上端相连通；所述第一循环泵设置于所述出液管与所述中空纤维柱相连的管路中。本发明系统投入成本低且S1蛋白产量高。 - link

• 检测新冠病毒的方法及试剂盒 - 本发明公开了一种检测新冠病毒的方法及试剂盒。其中，该方法包括以下步骤：1）采集样本；2）采用核酸释放剂提取核酸；3）采用LAMP扩增进行检测，其中，核酸释放剂包括：热敏蛋白酶1000U/L~10000U/L、Tris‑HCl 5~50 mmol/L、曲拉通X‑100体积百分比0.05%_{0.5%和金属离子螯合剂0.1}0.5mmol/L，其余为无菌水，热敏蛋白酶为≥55℃加热5~10分钟会完全失活的蛋白酶。应用本发明的检测新冠病毒的方法及试剂盒，检测新冠病毒，检测周期短，操作简单方便，检测结果通俗易懂，检测特异性高，检测成本低。 - link

• 一种新型冠状病毒拉曼光谱数据中心的构建方法 - 本发明公开了一种新型冠状病毒拉曼光谱数据中心的构建方法，该方法包括以下步骤：S1.构建新冠病毒结构蛋白拉曼光谱数据库；S2.构建新冠病毒核酸拉曼光谱数据库；S3.构建新冠病毒颗粒拉曼光谱数据库；S4.构建新冠病毒临床检测样本拉曼光谱数据库；将各新型冠状病毒拉曼光谱数据库存入新型冠状病毒拉曼光谱检测服务器构成新型冠状病毒拉曼光谱数据中心。本发明有效建立了一套完整的新型冠状病毒拉曼光谱数据库，为新冠病毒拉曼检测技术提供可靠的标准数据支撑，有效提高检测结果的准确性及置信度。 - link