Covid-19 Sentry

Contents

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

From Preprints

• Niclosamide Inhalation Powder Made by Thin-Film Freezing: Pharmacokinetic and Toxicology Studies in Rats and Hamsters -
  In this work, we have developed and tested in vivo a dry powder form of niclosamide made by thin-film freezing (TFF) and administered it by inhalation to rats and hamsters. The niclosamide dry powder, suitable for inhalation, is being developed as a therapeutic agent against COVID-19 infection. Niclosamide, a poorly water-soluble drug, is an interesting drug candidate because it was approved over 60 years ago for use as an anthelmintic medication, but recent studies demonstrated its potential as a broad-spectrum antiviral with a specific pharmacological effect against SARS-CoV-2 infection. In the past, clinical trials for other indications were terminated prior to completion due to low and highly variable oral bioavailability. In order to quickly address the current pandemic, targeting niclosamide directly to the lungs is rational to address the COVID-19 main clinical complications. Thin-film freezing technology was used to develop a niclosamide inhalation powder composition that exhibited acceptable aerosol performance with a fine particle fraction (FPF) of 86.0% and a mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of 1.11 microns and 2.84, respectively. This formulation not only proved to be safe after an acute three-day, multi-dose pharmacokinetic study in rats as evidenced by histopathology analysis, but also was able to achieve lung concentrations above the required IC50 and IC90 levels for at least 24 h after a single administration in a Syrian hamster model. To conclude, we successfully developed a niclosamide dry powder inhalation formulation by thin-film freezing for further scale-up and clinical testing against the COVID-19 infection. This approach overcomes limitations of niclosamide of poor oral bioavailability by targeting the drug directly to the primary site of infection, the lungs.
  🖺 Full Text HTML: Niclosamide Inhalation Powder Made by Thin-Film Freezing: Pharmacokinetic and Toxicology Studies in Rats and Hamsters
• TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor -
  Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor on macrophages and microglia that senses and responds to disease associated signals to regulate the phenotype of these innate immune cells. The TREM2 signaling pathway has been implicated in a variety of diseases ranging from neurodegeneration in the central nervous system to metabolic disease in the periphery. We report here that TREM2 is a thyroid hormone regulated gene and its expression in macrophages and microglia is stimulated by thyroid hormone. Both endogenous thyroid hormone and sobetirome, a synthetic thyroid hormone agonist drug, suppress pro-inflammatory cytokine production from myeloid cells including macrophages that have been treated with the SARS-CoV-2 spike protein which produces a strong, pro-inflammatory phenotype. Thyroid hormone agonism was also found to induce phagocytic behavior in microglia, a phenotype consistent with activation of the TREM2 pathway. The thyroid hormone antagonist NH-3 blocks the anti-inflammatory effects of thyroid hormone agonists and suppresses microglia phagocytosis. Finally, in a murine experimental autoimmune encephalomyelitis (EAE) multiple sclerosis model, treatment with Sob-AM2, a CNS-penetrating sobetirome prodrug, results in increased Trem2 expression in disease lesion resident myeloid cells which correlates with therapeutic benefit in the EAE clinical score and reduced damage to myelin. Our findings represent the first report of endocrine regulation of TREM2 and provide a unique opportunity to drug the TREM2 signaling pathway with orally active small molecule therapeutic agents.
  🖺 Full Text HTML: TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor
• A deep learning framework for real-time detection of novel pathogens during sequencing -
  Motivation: Novel pathogens evolve quickly and may emerge rapidly, causing dangerous outbreaks or even global pandemics. Next-generation sequencing is the state-of-the art in open-view pathogen detection, and one of the few methods available at the earliest stages of an epidemic, even when the biological threat is unknown. Analyzing the samples as the sequencer is running can greatly reduce the turnaround time, but existing tools rely on close matches to lists of known pathogens and perform poorly on novel species. Machine learning approaches can predict if single reads originate from more distant, unknown pathogens, but require relatively long input sequences and processed data from a finished sequencing run. Results: We present DeePaC-Live, a Python package for real-time pathogenic potential prediction directly from incomplete sequencing reads. We train deep neural networks to classify Illumina and Nanopore reads and integrate our models with HiLive2, a real-time Illumina mapper. DeePaC-Live outperforms alternatives based on machine learning and sequence alignment on simulated and real data, including SARS-CoV-2 sequencing runs. After just 50 Illumina cycles, we increase the true positive rate 80-fold compared to the live-mapping approach. The first 250bp of Nanopore reads, corresponding to 0.5s of sequencing time, are enough to yield predictions more accurate than mapping the finished long reads. Our approach could also be used for screening synthetic sequences against biosecurity threats. Availability: The code is available at: https://gitlab.com/dacs-hpi/deepac-live and https://gitlab.com/dacs-hpi/deepac. The package can be installed with Bioconda, Docker or pip.
  🖺 Full Text HTML: A deep learning framework for real-time detection of novel pathogens during sequencing
• How scientific reasoning correlates with health-related beliefs and behaviors during the COVID-19 pandemic? -
  We examined whether scientific reasoning is associated with health-related beliefs and behaviors over and above general analytic thinking ability in the general public (N = 783, aged 18–84). Health-related beliefs included: anti-vaccination attitudes, COVID-19 conspiracy beliefs, and generic health-related epistemically suspect beliefs. Scientific reasoning correlated with generic pseudoscientific and health-related conspiracy beliefs and COVID-19 conspiracy beliefs. Crucially, scientific reasoning was a stronger independent predictor of unfounded beliefs (including anti-vaccination attitudes) than general analytic thinking was; however, it had a more modest role in health-related behaviors.
  🖺 Full Text HTML: How scientific reasoning correlates with health-related beliefs and behaviors during the COVID-19 pandemic?
• Mechanism of Viral Glycoprotein Targeting by Membrane-associated-RING-CH Proteins -
  An emerging class of cellular inhibitory proteins has been identified that targets viral glycoproteins. These include the membrane-associated RING-CH (MARCH) family of E3 ubiquitin ligases that, among other functions, downregulate cell-surface proteins involved in adaptive immunity. The RING-CH domain of MARCH proteins is thought to function by catalyzing the ubiquitination of the cytoplasmic tails (CTs) of target proteins, leading to their degradation. MARCH proteins have recently been reported to target retroviral envelope glycoproteins (Env) and vesicular stomatitis virus G glycoprotein (VSV-G). However, the mechanism of antiviral activity remains poorly defined. Here we show that MARCH8 antagonizes the full-length forms of HIV-1 Env, VSV-G, Ebola virus glycoprotein (EboV-GP), and the spike (S) protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) thereby impairing the infectivity of virions pseudotyped with these viral glycoproteins. This MARCH8-mediated targeting of viral glycoproteins requires the E3 ubiquitin ligase activity of the RING-CH domain. We observe that MARCH8 protein antagonism of VSV-G is CT-dependent. In contrast, MARCH8-mediated targeting of HIV-1 Env, EboV-GP and SARS-CoV-2 S protein by MARCH8 does not require the CT, suggesting a novel mechanism of MARCH-mediated antagonism of these viral glycoproteins. Confocal microscopy data demonstrate that MARCH8 traps the viral glycoproteins in an intracellular compartment. We observe that the endogenous expression of MARCH8 in several relevant human cell types is rapidly inducible by type I interferon. These results help to inform the mechanism by which MARCH proteins exert their antiviral activity and provide insights into the role of cellular inhibitory factors in antagonizing the biogenesis, trafficking, and virion incorporation of viral glycoproteins.
  🖺 Full Text HTML: Mechanism of Viral Glycoprotein Targeting by Membrane-associated-RING-CH Proteins
• Variability in codon usage in Coronaviruses is mainly driven by mutational bias and selective constraints on CpG dinucleotide -
  The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third virus within the Orthocoronavirinae causing an emergent infectious disease in humans, the ongoing coronavirus disease 2019 pandemic (COVID-19). Due to the high zoonotic potential of these viruses, it is critical to unravel their evolutionary history of host species shift, adaptation and emergence. Only such knowledge can guide virus discovery, surveillance and research efforts to identify viruses posing a pandemic risk in humans. We present a comprehensive analysis of the composition and codon usage bias of the 82 Orthocoronavirinae members, infecting 47 different avian and mammalian hosts. Our results clearly establish that synonymous codon usage varies widely among viruses and is only weakly dependent on the type of host they infect. Instead, we identify mutational bias towards AT-enrichment and selection against CpG dinucleotides as the main factors responsible of the codon usage bias variation. Further insight on the mutational equilibrium within Orthocoronavirinae revealed that most coronavirus genomes are close to their neutral equilibrium, the exception is the three recently-infecting human coronaviruses, which lie further away from the mutational equilibrium than their endemic human coronavirus counterparts. Finally, our results suggest that while replicating in humans SARS-CoV-2 is slowly becoming AT-richer, likely until attaining a new mutational equilibrium.
  🖺 Full Text HTML: Variability in codon usage in Coronaviruses is mainly driven by mutational bias and selective constraints on CpG dinucleotide
• Computational Investigation of Increased Virulence and Pathogenesis of SARS-CoV-2 Lineage B.1.1.7 -
  New variants of SARS-CoV-2 are being reported worldwide. More specifically, the variants reported in South Africa (501Y.V2) and United Kingdom (B.1.1.7) were found to be more contagious than the wild type. There are also speculations that the variants might evade the host immune responses induced by currently available vaccines and develop resistance to drugs under consideration. The first step of viral infection in COVID-19, occurs through the interaction of receptor binding domain (RBD) of the spike protein with peptidase domain of the human ACE-2 (hACE-2) receptor. So, possibly the mutations in the RBD domain of spike protein in the new variants could modulate the protein-protein interaction with hACE-2 receptor leading to the increased virulence. In this study, we aim to get molecular level understanding into the mechanism behind the increased infection rate due to such mutations in these variants. We have computationally studied the interaction of the spike protein in both wild-type and B.1.1.7 variant with hACE-2 receptor using combined molecular dynamics and binding free energy calculations using molecular mechanics-Generalized Born surface area (MM-GBSA) approach. The binding free energies computed using configurations from minimization run and low temperature simulation show that mutant variant of spike protein has increased binding affinity for hACE-2 receptor (i.e. {triangleup}{triangleup}G(N501Y,A570D) is in the range -20.4 to -21.4 kcal/mol)The residue-wise decomposition analysis and intermolecular hydrogen bond analysis evidenced that the N501Y mutation has increased interaction between RBD of spike protein with ACE-2 receptor. We have also carried out calculations using density functional theory and the results evidenced the increased interaction between three pairs of residues (TYR449 (spike)-ASP38 (ACE-2), TYR453-HIE34 and TYR501-LYS353) in the variant that could be attributed to its increased virulence. The free energies of wild-type and mutant variants of the spike protein computed from MM-GBSA approach suggests that latter variant is stable by about -10.4 kcal/mol when compared to wild type suggesting that it will be retained in the evolution due to increased stability. We demonstrate that with the use of the state-of-the art of computational approaches, we can in advance predict the more virulent nature of variants of SARS-CoV-2 and alert the world health-care system.
  🖺 Full Text HTML: Computational Investigation of Increased Virulence and Pathogenesis of SARS-CoV-2 Lineage B.1.1.7
• 40 minutes RT-qPCR Assay for Screening Spike N501Y and HV69-70del Mutations -
  A one-step reverse transcription and real-time PCR (RT-qPCR) test was developed for rapid screening (40 minutes) of the Spike N501Y and HV69-70del mutations in SARS-CoV-2 positive samples. The test also targets a conserved region of SARS-CoV-2 Orf1ab as an internal control. The samples containing both the N501Y and HV69-70del mutations are concluded as VOC-202012/01 positive. Samples suspected to be positive for B.1.351 or P.1 are the N501Y positive and HV69-70del negative cases. Limit of detection (LOD) of the kit for Orf1ab target is 500 copies/mL, while that of the N501, Y501 and HV69-70del targets are 5000 copies/mL. The developed assay was applied to 165 clinical samples containing SARS-CoV-2 from 32 different lineages. The SARS-CoV-2 lineages were determined via the next-generation sequencing (NGS). The RT-qPCR results were in 100% agreement with the NGS results that 19 samples were N501Y and HV69-70del positive, 10 samples were N501Y positive and HV69-70del negative, 1 sample was N501Y negative and HV69-70del positive, and 135 samples were N501Y and HV69-70del negative. All the VOC-202012/01 positive samples were detected in people who have traveled from England to Turkey. The RT-qPCR test and the Sanger sequencing was further applied to 1000 SARS-CoV-2 positive clinical samples collected in Jan2021 from the 81 different provinces of Turkey. The RT-qPCR results were in 100% agreement with the Sanger sequencing results that 32 samples were N501Y positive and HV69-70del negative, 4 samples were N501Y negative and HV69-70del positive, 964 samples were N501Y and HV69-70del negative. The specificity of the 40 minutes RT-qPCR assay relative to the sequencing-based technologies is 100%. The developed assay is an advantageous tool for timely and representative estimation of prevalence of the N501Y positive variants because it allows testing a much higher portion of the SARS-CoV-2 positives in much lower time compared to the sequencing-based technologies.
  🖺 Full Text HTML: 40 minutes RT-qPCR Assay for Screening Spike N501Y and HV69-70del Mutations
• Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2 -
  A detailed understanding of antibody-based SARS-CoV-2 immunity has critical implications for overcoming the COVID-19 pandemic and for informing on vaccination strategies. In this study, we evaluated the dynamics of the SARS-CoV-2 antibody response in a cohort of 963 recovered individuals over a period of 10 months. Investigating a total of 2,146 samples, we detected an initial SARS-CoV-2 antibody response in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of recovered patients demonstrated exceptional SARS-CoV-2 neutralizing activity, defining them as elite neutralizers. These individuals also possessed effective cross-neutralizing IgG antibodies to SARS-CoV-1 without any known prior exposure to this virus. By applying multivariate statistical modeling, we found that sero-reactivity, age, time since disease onset, and fever are key factors predicting SARS-CoV-2 neutralizing activity in mild courses of COVID-19. Investigating longevity of the antibody response, we detected loss of anti-spike reactivity in 13% of individuals 10 months after infection. Moreover, neutralizing activity had an initial half-life of 6.7 weeks in serum versus 30.8 weeks in purified IgG samples indicating the presence of a more stable and long-term memory IgG B cell repertoire in the majority of individuals recovered from COVID-19. Our results demonstrate a broad spectrum of the initial SARS-CoV-2 neutralizing antibody response depending on clinical characteristics, with antibodies being maintained in the majority of individuals for the first 10 months after mild course of COVID-19.
  🖺 Full Text HTML: Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2
• A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques -
  The deployment of a vaccine that limits transmission and disease likely will be required to end the Coronavirus Disease 2019 (COVID-19) pandemic. We recently described the protective activity of an intranasally-administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (S) protein (ChAd-SARS-CoV-2-S) in the upper and lower respiratory tract of mice expressing the human angiotensin-converting enzyme 2 (ACE2) receptor. Here, we show the immunogenicity and protective efficacy of this vaccine in non-human primates. Rhesus macaques were immunized with ChAd-Control or ChAd-SARS-CoV-2-S and challenged one month later by combined intranasal and intrabronchial routes with SARS-CoV-2. A single intranasal dose of ChAd-SARS-CoV-2-S induced neutralizing antibodies and T cell responses and limited or prevented infection in the upper and lower respiratory tract after SARS-CoV-2 challenge. As this single intranasal dose vaccine confers protection against SARS-CoV-2 in non-human primates, it is a promising candidate for limiting SARS-CoV-2 infection and transmission in humans.
  🖺 Full Text HTML: A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques
• Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization -
  The Covid-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Two monoclonal antibody (mAb) therapeutics have received emergency use authorization, and more are in the pipeline. Furthermore, multiple vaccine constructs have shown promise, including two with ~95% protective efficacy against Covid-19. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. Considerable viral evolution has occurred since, including variants with a D614G mutation that have become dominant. Viruses with this mutation alone do not appear to be antigenically distinct, however. Recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK and B.1.351 in South Africa is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a number of mAbs to the receptor-binding domain (RBD). It is modestly more resistant to convalescent plasma (~3 fold) and vaccinee sera (~2 fold). Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple potent mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (~11-33 fold) and vaccinee sera (~6.5-8.6 fold). B.1.351 and emergent variants with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.
  🖺 Full Text HTML: Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization
• A novel SARS-CoV-2 related coronavirus in bats from Cambodia -
  Knowledge of the origin and reservoir of the coronavirus responsible for the ongoing COVID-19 pandemic is still fragmentary. To date, the closest relatives to SARS-CoV-2 have been detected in Rhinolophus bats sampled in the Yunnan province, China. Here we describe the identification of SARS-CoV-2 related coronaviruses in two Rhinolophus shameli bats sampled in Cambodia in 2010. Metagenomic sequencing identified nearly identical viruses sharing 92.6% nucleotide identity with SARS-CoV-2. Most genomic regions are closely related to SARS-CoV-2, with the exception of a small region corresponding to the spike N terminal domain. The discovery of these viruses in a bat species not found in China indicates that SARS-CoV-2 related viruses have a much wider geographic distribution than previously understood, and suggests that Southeast Asia represents a key area to consider in the ongoing search for the origins of SARS-CoV-2, and in future surveillance for coronaviruses.
  🖺 Full Text HTML: A novel SARS-CoV-2 related coronavirus in bats from Cambodia
• Immunogenic Potential of DNA Vaccine candidate, ZyCoV-D against SARS-CoV-2 in Animal Models -
  Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially originated in China in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. Huge efforts were undertaken to bring the COVID-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. We developed a candidate vaccine ZyCoV-D comprising of a DNA plasmid vector carrying the gene encoding the spike protein (S) of the SARS-CoV-2 virus. The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme (ACE-2) receptor. The DNA plasmid construct was transformed into E. coli cells for large scale production. The immunogenicity potential of the plasmid DNA has been evaluated in mice, guinea pig, and rabbit models by intradermal route at 25, 100 and 500g dose. Based on the animal studies proof-of-concept has been established and preclinical toxicology (PCT) studies were conducted in rat and rabbit model. Preliminary animal study demonstrates that the candidate DNA vaccine induces antibody response including neutralizing antibodies against SARS-CoV-2 and also provided Th-1 response as evidenced by elevated IFN-{gamma} levels.
  🖺 Full Text HTML: Immunogenic Potential of DNA Vaccine candidate, ZyCoV-D against SARS-CoV-2 in Animal Models
• Elevated HScore is Associated with Poor Clinical Outcomes in COVID-19, Even in the Absence of Secondary Hemophagocytic Lymphohistiocytosis. -

  Introduction: Patients with Coronavirus Disease 2019 (COVID-19) frequently experience a hyperinflammatory syndrome, that leads to unfavorable outcomes. This condition resembles Secondary Hemophagocytic Lymphohistiocytosis (sHLH) described in neoplastic, rheumatic and other infectious diseases. However, it has not been prospectively studied on these patients. A scoring system (HScore) has been validated for sHLH, and recently proposed to evaluate hyperinflammation in COVID-19. Methods: 143 patients aged ≥18 years admitted because of COVID-19 were enrolled in a prospective, single-center, cohort study. HScore was calculated within the 72 hours since admission. The incidence of sHLH during hospitalization was evaluated. Additionally, the relationship between HScore ≥130 points and either the requirement of mechanical ventilation or 60-days mortality was explored. Results: The median age of enrolled patients was 57 (21-100), and 63.6% were male. The median HScore was 96 (33-169). One patient was diagnosed with sHLH (incidence 0,7%), due to a HScore of 169. After adjusting for age, sex, comorbidities and obesity, HScore ≥130 was independently associated with the composite clinical outcome (HR 2.13, p=0.022). Conclusion: sHLH is not frequent among COVID-19 patients. HScore can efficiently predict the risk for poor outcomes.

  🖺 Full Text HTML: Elevated HScore is Associated with Poor Clinical Outcomes in COVID-19, Even in the Absence of Secondary Hemophagocytic Lymphohistiocytosis.
• Colder and drier winter conditions are associated with greater SARS-CoV-2 transmission: a regional study of the first epidemic wave in north-west hemisphere countries. -

  Higher transmissibility of SARS-CoV-2 in cold and dry weather conditions has been hypothesized since the onset of the COVID-19 pandemic but the level of epidemiological evidence remains low. During the first wave of the pandemic for Spain, Italy, France, Portugal, Canada and USA presented an early spread, a heavy COVID-19 burden, and low initial public health response until lockdowns. We used regional death counts as a proxy for infections while diagnostic tests remained limited and calculated a basic reproduction number (R0) in 63 regions. After adjusting for population density, early spread of the epidemic, and aged population, temperature and humidity were negatively associated to SARS-CoV-2 transmissibility. A -1g/m3 lower mean absolute humidity was associated with a 0.15-unit higher R0. Below 10°C, a 1°C-higher temperature was associated with a 0.16-unit lower R0. Our results confirm a strong dependency of SARS-CoV-2 transmissibility to weather conditions in the absence of control measures. The initiation of the second wave in north-west hemisphere countries was likely triggered by the transition from summer- to winter-like conditions. High levels of restrictions to social activities should be maintained until spring to avoid or limit a third wave.

  🖺 Full Text HTML: Colder and drier winter conditions are associated with greater SARS-CoV-2 transmission: a regional study of the first epidemic wave in north-west hemisphere countries.

From Clinical Trials

• Dexamethasone for COVID-19 - Condition:   Covid19
  Intervention:   Drug: Dexamethasone
  Sponsor:   University of Oklahoma
  Not yet recruiting

• Phase III Study of AZD7442 for Treatment of COVID-19 in Outpatient Adults - Condition:   COVID-19
  Interventions:   Drug: AZD7442;   Drug: Placebo
  Sponsor:   AstraZeneca
  Not yet recruiting

• Fluvoxamine Administration in Moderate SARS-CoV-2 (COVID-19) Infected Patients - Condition:   Covid19
  Interventions:   Drug: Placebo;   Drug: Fluvoxamine
  Sponsor:   SigmaDrugs Research Ltd.
  Recruiting

• The (HD)IVACOV Trial (The High-Dose IVermectin Against COVID-19 Trial) - Condition:   Covid19
  Interventions:   Drug: Ivermectin 0.6mg/kg/day;   Drug: Ivermectin 1.0mg/kg/day;   Drug: Placebo;   Drug: Hydroxychloroquine
  Sponsor:   Corpometria Institute
  Not yet recruiting

• APT™ T3X on the COVID-19 Contamination Rate - Condition:   COVID-19
  Interventions:   Drug: Tetracycline hydrochloride 3%;   Drug: Placebo
  Sponsors:   University of Nove de Julho;   Santa Casa de Misericórdia de Porto Alegre
  Not yet recruiting

• A Study of ORTD-1 in Patients Hospitalized With COVID-19 Related Pneumonia - Condition:   COVID-19
  Interventions:   Drug: ORTD-1 low dose;   Drug: ORTD-1 mid dose;   Drug: ORTD-1 high dose;   Other: Vehicle control
  Sponsor:   Oryn Therapeutics, LLC
  Recruiting

• Efficacy of Nano-Ivermectin Impregnated Masks in Prevention of Covid-19 Among Healthy Contacts and Medical Staff - Condition:   Covid-19
  Intervention:   Other: ivermectin impregnated mask
  Sponsor:   South Valley University
  Recruiting

• COVID-19 Immunologic Antiviral Therapy With Omalizumab - Condition:   Covid19
  Interventions:   Biological: Omalizumab;   Other: Placebo
  Sponsor:   McGill University Health Centre/Research Institute of the McGill University Health Centre
  Not yet recruiting

• IMUNOR® Preparation in the Prevention of COVID-19 - Condition:   Covid19
  Intervention:   Drug: IMUNOR
  Sponsor:   University Hospital Ostrava
  Not yet recruiting

• Clinical Experimentation With Tenofovir Disoproxyl Fumarate and Emtricitabine for COVID-19 - Condition:   Covid19
  Interventions:   Drug: Vitamin C 500 MG Oral Tablet;   Drug: Tenofovir disoproxyl fumarate 300 MG Oral Tablet;   Drug: Tenofovir disoproxyl fumarate 300 MG plus emtricitabine 200 MG Oral Tablet
  Sponsors:   Universidade Federal do Ceara;   Conselho Nacional de Desenvolvimento Científico e Tecnológico;   São José Hospital for Infectious Diseases - HSJ;   Central Laboratory of Public Health of Ceará - Lacen-CE
  Recruiting

• Safety and Efficacy of Doxycycline and Rivaroxaban in COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Doxycycline Tablets;   Drug: Rivaroxaban 15Mg Tab;   Combination Product: Hydroxychloroquine and Azithromycin
  Sponsor:   Yaounde Central Hospital
  Recruiting

• Phase IIb Clinical Trial of Recombinant Novel Coronavirus Pneumonia (COVID-19) Vaccine (Sf9 Cells) - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 vaccine (Sf9 cells);   Biological: Placebo
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   West China Hospital
  Not yet recruiting

• Famotidine vs Placebo for the Treatment of Non-Hospitalized Adults With COVID-19 - Condition:   Covid-19
  Interventions:   Drug: Famotidine;   Drug: Placebo
  Sponsors:   Northwell Health;   Cold Spring Harbor Laboratory
  Recruiting

• Antiseptic Mouth Rinses to Reduce Salivary Viral Load in COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: Betadine© bucal 100 mg/ml;   Drug: Oximen® 3%;   Drug: Clorhexidine Dental PHB©;   Drug: Vitis Xtra Forte©;   Drug: Distilled Water
  Sponsors:   Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana;   Hospital Universitario Fundación Jiménez Díaz;   Hospital Universitario General de Villalba;   Hospital Universitario Infanta Elena;   Hospital Universitario Virgen de la Arrixaca;   Hospital Clínico Universitario de Valencia;   Dentaid SL
  Completed

• COVID-19 and Pregnancy: Placental and Immunological Impacts - Condition:   Covid19
  Intervention:   Other: Specimens specific for the study
  Sponsor:   Hopital Foch
  Recruiting

From PubMed

• Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein - Most human monoclonal antibodies (mAbs) neutralizing SARS-CoV-2 recognize the spike (S) protein receptor-binding domain and block virus interactions with the cellular receptor angiotensin-converting enzyme 2. We describe a panel of human mAbs binding to diverse epitopes on the N-terminal domain (NTD) of S protein from SARS-CoV-2 convalescent donors and found a minority of these possessed neutralizing activity. Two mAbs (COV2-2676 and COV2-2489) inhibited infection of authentic SARS-CoV-2 and...

• BRD2 inhibition blocks SARS-CoV-2 infection in vitro by reducing transcription of the host cell receptor ACE2 - SARS-CoV-2 infection of human cells is initiated by the binding of the viral Spike protein to its cell-surface receptor ACE2. We conducted an unbiased CRISPRi screen to uncover druggable pathways controlling Spike protein binding to human cells. We found that the protein BRD2 is an essential node in the cellular response to SARS-CoV-2 infection. BRD2 is required for ACE2 transcription in human lung epithelial cells and cardiomyocytes, and BRD2 inhibitors currently evaluated in clinical trials...

• Host-directed therapies against early-lineage SARS-CoV-2 retain efficacy against B.1.1.7 variant - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths worldwide and massive societal and economic burden. Recently, a new variant of SARS-CoV-2, known as B.1.1.7, was first detected in the United Kingdom and is spreading in several other countries, heightening public health concern and raising questions as to the resulting effectiveness of vaccines and therapeutic interventions. We and others previously...

• A PCR amplicon-based SARS-CoV-2 replicon for antiviral evaluation - The development of specific antiviral compounds to SARS-CoV-2 is an urgent task. One of the obstacles for the antiviral development is the requirement of biocontainment because infectious SARS-CoV-2 must be handled in a biosafety level-3 laboratory. Replicon, a non-infectious self-replicative viral RNA, could be a safe and effective tool for antiviral evaluation. Herein, we generated a PCR-based SARS-CoV-2 replicon. Eight fragments covering the entire SARS-CoV-2 genome except S, E, and M genes...

• Molecular Docking of Azithromycin, Ritonavir, Lopinavir, Oseltamivir, Ivermectin and Heparin Interacting with Coronavirus Disease 2019 Main and Severe Acute Respiratory Syndrome Coronavirus-2 3C-Like Proteases - In the current pandemic situation raised due to COVID-19, drug reuse is emerging as the first line of treatment. The viral agent that causes this highly contagious disease and the acute respiratory syndrome coronavirus (SARS-CoV) share high nucleotide similarity. Therefore, it is structurally expected that many existing viral targets are similar to the first SARS-CoV, probably being inhibited by the same compounds. Here, we selected two viral proteins based on their vital role in the viral life...

• Development of a Cell-Based Luciferase Complementation Assay for Identification of SARS-CoV-2 3CL(pro) Inhibitors - The 3C-like protease (3CL^(pro)) of SARS-CoV-2 is considered an excellent target for COVID-19 antiviral drug development because it is essential for viral replication and has a cleavage specificity distinct from human proteases. However, drug development for 3CL^(pro) has been hindered by a lack of cell-based reporter assays that can be performed in a BSL-2 setting. Current efforts to identify 3CL^(pro) inhibitors largely rely upon in vitro screening, which fails to account for cell permeability...

• Protective Effects of Lactoferrin against SARS-CoV-2 Infection In Vitro - SARS-CoV-2 is a newly emerging virus that currently lacks curative treatments. Lactoferrin (LF) is a naturally occurring non-toxic glycoprotein with broad-spectrum antiviral, immunomodulatory and anti-inflammatory effects. In this study, we assessed the potential of LF in the prevention of SARS-CoV-2 infection in vitro. Antiviral immune response gene expression was analyzed by qRT-PCR in uninfected Caco-2 intestinal epithelial cells treated with LF. An infection assay for SARS-CoV-2 was...

• Repositioning of histamine H(1) receptor antagonist: Doxepin inhibits viropexis of SARS-CoV-2 Spike pseudovirus by blocking ACE2 - The spread of the corona virus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been intensifying in the past year, posing a huge threat to global health. There is an urgent need for effective drugs and vaccines to fight the COVID-19, but their advent may not be quite fast. Drug repurposing is a feasible strategy in the current situation, which could greatly shorten drug development time and help to response quickly to the novel virus...

• The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial - BACKGROUND: Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset.

• Pragmatic, open-label, single-center, randomized, phase II clinical trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus in patients with severe pneumonia secondary to COVID-19: The TACROVID trial protocol - INTRODUCTION: Some COVID-19 patients evolve to severe lung injury and systemic hyperinflammatory syndrome triggered by both the coronavirus infection and the subsequent host-immune response. Accordingly, the use of immunomodulatory agents has been suggested but still remains controversial. Our working hypothesis is that methylprednisolone pulses and tacrolimus may be an effective and safety drug combination for treating severe COVID-19 patients.

• Polyphenols as promising biologically active substances for preventing SARS-CoV-2: A review with research evidence and underlying mechanisms - Currently, antiviral drugs and/or vaccines are not yet available to treat or prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we narrated the available data, from credible publishers, regarding the possible role of polyphenols and natural extracts-containing polyphenols in the prevention of coronavirus disease 2019 (COVID-19), and their immune-boosting properties. It was revealed that polyphenols could be considered as promising biologically active substances...

• Luteolin and abyssinone II as potential inhibitors of SARS-CoV-2: an in silico molecular modeling approach in battling the COVID-19 outbreak - CONCLUSIONS: Conclusively, the current study proposes that luteolin and abyssinone II might act as potential therapeutic candidates for SARS-CoV-2 infection. In vivo and in vitro experiments, however, should be taken under consideration to determine the efficiency and to demonstrate the mechanism of action.

• Identifying anti-coronavirus peptides by incorporating different negative datasets and imbalanced learning strategies - As the current worldwide outbreaks of the SARS-CoV-2, it is urgently needed to develop effective therapeutic agents for inhibiting the pathogens or treating the related diseases. Antimicrobial peptides (AMP) with functional activity against coronavirus could be a considerable solution, yet there is no research for identifying anti-coronavirus (anti-CoV) peptides with the computational approach. In this study, we first investigated the physiochemical and compositional properties of the collected...

• Temporal development and neutralising potential of antibodies against SARS-CoV-2 in hospitalised COVID-19 patients: An observational cohort study - Antibody responses are important in the control of viral respiratory infection in the human host. What is not clear for SARS-CoV-2 is how rapidly this response occurs, or when antibodies with protective capability evolve. Hence, defining the events of SARS-CoV-2 seroconversion and the time frame for the development of antibodies with protective potential may help to explain the different clinical presentations of COVID-19. Furthermore, accurate descriptions of seroconversion are needed to inform...

• Targeting cyclooxygenase enzyme for the adjuvant COVID-19 therapy - Despite vigorous efforts, the COVID-19 pandemic continues to take a toll on the global health. The contemporary therapeutic regime focused on the viral spike proteins, viral 3CL protease enzyme, immunomodulation, inhibition of viral replication, and providing a symptomatic relief encouraged the repurposing of drugs to meet the urgency of treatment. Similarly, the representative drugs that proved beneficial to alleviate SARS-CoV-1, MERS-CoV, HIV, ZIKV, H1N1, and malarial infection in the past...

From Patent Search

• COVID-19 CLASSIFICATION RECOGNITION METHOD BASED ON CT IMAGES OF LUNGS - - link

• A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof - - link

• Covid 19 - Chewing Gum - - link

• STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19 - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - link

• Fahrzeuglüftungssystem und Verfahren zum Betreiben eines solchen Fahrzeuglüftungssystems -

  Die Erfindung betrifft ein Fahrzeuglüftungssystem (1) zum Belüften einer Fahrgastzelle (2) eines Fahrzeugs (3), mit einem Umluftpfad (5). Die Erfindung ist gekennzeichnet durch eine wenigstens abschnittsweise in einen Umluftansaugbereich (4) des Umluftpads (5) hineinreichende Sterilisationseinrichtung (6), wobei die Sterilisationseinrichtung (6) dazu eingerichtet ist von einem aus der Fahrgastzelle (2) entnommenen Luftstrom getragene Schadstoffe zu inaktivieren und/oder abzutöten.

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• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• "AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2." - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex. - link

• Mund-Nasen-Bedeckung -

  Mund-Nasen-Bedeckung (1), wobei die Mund-Nasen-Bedeckung (1) mindestens an einem Ohr eines Trägers magnetisch befestigbar ist.

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• Haptens, hapten conjugates, compositions thereof and method for their preparation and use - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels. - link