Covid-19 Sentry

Contents

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

From Preprints

• The Pandemic and my PhD: Lessons from a Policy Research Placement with the Reset Initiative -
  In this brief reflection, I explore three key lessons learned from conducting a policy research placement during the COVID-19 pandemic. I explore how the placement changed my perspective on my PhD research, working life, and suggest how academics may better engage with policymakers in the future.
  🖺 Full Text HTML: The Pandemic and my PhD: Lessons from a Policy Research Placement with the Reset Initiative
• Making Virtual Teams Work: Redesigning Virtual Collaboration for the Future -
  The COVID-19 pandemic has shifted how many teams work, from face-to-face interactions to remote and hybrid forms of collaboration. Even at its best, though, virtual collaboration remains less effective than face-to-face collaboration, leaving millions of workers with both the temporary and permanent challenges of virtual work. Virtual collaboration as we know it was designed in and for a colocated world without prioritizing diverse needs. Design is uniquely positioned to not only alleviate these ails but even make virtual teams strategically advantageous by developing solutions specifically for hybrid virtual collaboration. To do so, designers must incorporate attributes that make virtual collaboration “work”. This article provides background on communication technologies before summarizing the attributes of collaboration and leadership that “work” for effective virtual collaboration. We then highlight several outstanding concerns and possibilities as an impetus for designers and researchers to develop solutions to the challenges of sustained remote and hybrid collaboration. In doing so, we seek to motivate designers and researchers to redesign the artifact of virtual work itself for the fundamental needs of collaboration.
  🖺 Full Text HTML: Making Virtual Teams Work: Redesigning Virtual Collaboration for the Future
• SARS-CoV-2 infection causes transient olfactory dysfunction in mice -
  Olfactory dysfunction caused by SARS-CoV-2 infection represents as one of the most predictive and common symptoms in COVID-19 patients. However, the causal link between SARS-CoV-2 infection and olfactory disorders remains lacking. Herein we demonstrate intranasal inoculation of SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), resulting in transient olfactory dysfunction in humanized ACE2 mice. The sustentacular cells and Bowman’s gland cells in OE were identified as the major targets of SARS-CoV-2 before the invasion into olfactory sensory neurons. Remarkably, SARS-CoV-2 infection triggers cell death and immune cell infiltration, and impairs the uniformity of OE structure. Combined transcriptomic and proteomic analyses reveal the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptors in OE from the infected animals. Overall, our mouse model recapitulates the olfactory dysfunction in COVID-19 patients, and provides critical clues to understand the physiological basis for extrapulmonary manifestations of COVID-19.
  🖺 Full Text HTML: SARS-CoV-2 infection causes transient olfactory dysfunction in mice
• Epidemiological transcriptomic data supports BCG protection in viral diseases including COVID-19 -
  Epidemiological evidence suggests that Bacille Calmette-Guerin (BCG) vaccine induced trained immunity protects against non-specific infections including coronavirus disease 2019 (COVID-19). A recent clinical trial has also supported BCG protection in viral respiratory infections in general, with multiple COVID-19 specific trials currently ongoing. The durability and mechanism of BCG trained immunity however remain unclear. An integrative analysis of available epidemiological transcriptomic data related to BCG vaccination and viral respiratory infections, along with transcriptomic alterations reported in COVID-19, is presented here toward addressing this gap. Results show that BCG vaccination leads to a very long-lasting transcriptomic changes which mimic viral infections by upregulated antiviral defense response, and oppose viral infections by downregulated myeloid cell activation mediated immune response. Antiviral defense upregulation is consistent with the present concept of trained immunity, whereas downregulation of myeloid cell activation seems directionally inconsistent, with enhancement of innate immune response considered to characterize trained immunity. The present finding is however in consonance with recent retrospective cohort study and clinical trial evidence that shows no association of BCG vaccination with systemic inflammation, alleviating the concern that the vaccine may add to inflammatory response and worsen severe COVID-19. In conclusion, the present analysis offers transcriptomic support to the existing epidemiological evidence of lower prevalence and mortality of COVID-19 in countries with childhood BCG vaccination policy.
  🖺 Full Text HTML: Epidemiological transcriptomic data supports BCG protection in viral diseases including COVID-19
• Highly potent bispecific sybodies neutralize SARS-CoV-2 -
  The COVID-19 pandemic has resulted in a global crisis. Here, we report the generation of synthetic nanobodies, known as sybodies, against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. We identified a sybody pair (Sb#15 and Sb#68) that can bind simultaneously to the RBD, and block ACE2 binding, thereby neutralizing pseudotyped and live SARS-CoV-2 viruses. Cryo-EM analyses of the spike protein in complex with both sybodies revealed symmetrical and asymmetrical conformational states. In the symmetric complex each of the three RBDs were bound by both sybodies, and adopted the up conformation. The asymmetric conformation, with three Sb#15 and two Sb#68 bound, contained one down RBD, one up-out RBD and one up RBD. Bispecific fusions of the sybodies increased the neutralization potency 100-fold, as compared to the single binders. Our work demonstrates that linking two binders that recognize spatially-discrete binding sites result in highly potent SARS-CoV-2 inhibitors for potential therapeutic applications.
  🖺 Full Text HTML: Highly potent bispecific sybodies neutralize SARS-CoV-2
• Protective efficacy of a SARS-CoV-2 DNA Vaccine in wild-type and immunosuppressed Syrian hamsters -
  A worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages of research and development, including several vaccines in phase 1, 2 and 3 clinical trials. A relatively small number of these vaccines have been evaluated in SARS-CoV-2 disease models, and fewer in a severe disease model. Here, a SARS-CoV-2 DNA targeting the spike protein and delivered by jet injection, nCoV-S(JET), elicited neutralizing antibodies in hamsters and was protective in both wild-type and transiently immunosuppressed hamster models. This study highlights the DNA vaccine, nCoV-S(JET), we developed has a great potential to move to next stage of preclinical studies, and it also demonstrates that the transiently-immunosuppressed Syrian hamsters, which recapitulate severe and prolonged COVID-19 disease, can be used for preclinical evaluation of the protective efficacy of spike-based COVID-19 vaccine.
  🖺 Full Text HTML: Protective efficacy of a SARS-CoV-2 DNA Vaccine in wild-type and immunosuppressed Syrian hamsters
• CD127 imprints functional heterogeneity to diversify monocyte responses in human inflammatory diseases -
  Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in patients with infectious and inflammatory conditions such as COVID-19 and rheumatoid arthritis. Multiple genomic and functional approaches revealed unique gene signatures of M127 and unified anti-inflammatory properties imposed by the CD127-STAT5 axis. M127 expansion correlated with mild COVID-19 disease outcomes. Thereby, we phenotypically and molecularly characterized a human monocyte subset marked by CD127 that retained anti-inflammatory properties within the pro-inflammatory environments, uncovering remarkable functional diversity among monocytes and signifying M127 as a potential therapeutic target for human inflammatory disorders.
  🖺 Full Text HTML: CD127 imprints functional heterogeneity to diversify monocyte responses in human inflammatory diseases
• A benchmarking study of SARS-CoV-2 whole-genome sequencing protocols using COVID-19 patient samples -
  The COVID-19 pandemic is a once-in-a-lifetime event, exceeding mortality rates of the flu pandemics from the 1950’s and 1960’s. Whole-genome sequencing (WGS) of SARS-CoV-2 plays a critical role in understanding the disease. Performance variation exists across SARS-CoV-2 viral WGS technologies, but there is currently no benchmarking study comparing different WGS sequencing protocols. We compared seven different SARS-CoV-2 WGS library protocols using RNA from patient nasopharyngeal swab samples under two storage conditions. We constructed multiple WGS libraries encompassing three different viral inputs: 1,000,000, 250,000 and 1,000 copies. Libraries were sequenced using two distinct platforms with varying sequencing depths and read lengths. We found large differences in mappability and genome coverage, and variations in sensitivity, reproducibility and precision of single-nucleotide variant calling across different protocols. We ranked the performance of protocols based on six different metrics. Our results indicated that the most appropriate protocol depended on viral input amount and sequencing depth. Our findings offer guidance in choosing appropriate WGS protocols to characterize SARS-CoV-2 and its evolution.
  🖺 Full Text HTML: A benchmarking study of SARS-CoV-2 whole-genome sequencing protocols using COVID-19 patient samples
• Susceptibility of well-differentiated airway epithelial cell cultures from domestic and wildlife animals to SARS-CoV-2 -
  Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally, and the number of cases continues to rise all over the world. Besides humans, the zoonotic origin, as well as intermediate and potential spillback host reservoirs of SARS-CoV-2 are unknown. To circumvent ethical and experimental constraints, and more importantly, to reduce and refine animal experimentation, we employed our airway epithelial cell (AEC) culture repository composed of various domesticated and wildlife animal species to assess their susceptibility to SARS-CoV-2. In this study, we inoculated well-differentiated animal AEC cultures of monkey, cat, ferret, dog, rabbit, pig, cattle, goat, llama, camel, and two neotropical bat species with SARS-CoV-2. We observed that SARS-CoV-2 only replicated efficiently in monkey and cat AEC culture models. Whole-genome sequencing of progeny virus revealed no obvious signs of nucleotide transitions required for SARS-CoV-2 to productively infect monkey and cat epithelial airway cells. Our findings, together with the previously reported human-to-animal spillover events warrants close surveillance to understand the potential role of cats, monkeys, and closely related species as spillback reservoirs for SARS-CoV-2.
  🖺 Full Text HTML: Susceptibility of well-differentiated airway epithelial cell cultures from domestic and wildlife animals to SARS-CoV-2
• In Vitro Efficacy of “Essential Iodine Drops” Against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) -
  Background: Aerosolization of respiratory droplets is considered the main route of coronavirus disease 2019 (COVID-19). Therefore, reducing the viral load of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) shed via respiratory droplets is potentially an ideal strategy to prevent the spread of the pandemic. The in vitro virucidal activity of intranasal Povidone-Iodine (PVP-I) has been demonstrated recently to reduce SARS-CoV-2 viral titres. This study evaluated the virucidal activity of the aqueous solution of Iodine-V (a clathrate complex formed by elemental iodine and fulvic acid) as in Essential Iodine Drops (EID) with 200 microgram elemental iodine/ml content against SARS-CoV-2 to ascertain whether it is a better alternative to PVP-I. Methods: SARS-CoV-2 (USAWA1/2020 strain) virus stock was prepared by infecting Vero 76 cells (ATCC CRL-1587) until cytopathic effect (CPE). The virucidal activity of EID against SARS-CoV-2 was tested in three dilutions (1:1; 2:1 and 3:1) in triplicates by incubating at room temperature (22 +/- 2 Celsius) for either 60 or 90 seconds. The surviving viruses from each sample were quantified by a standard end-point dilution assay. Results: EID (200 microgram iodine/ml) after exposure for 60 and 90 seconds was compared to controls. In both cases, the viral titre was reduced by 99% (LRV 2.0). The 1:1 dilution of EID with virus reduced SARS-CoV-2 virus from 31,623 cell culture infectious dose 50% (CCCID50) to 316 CCID50 within 90 seconds. Conclusion: Substantial reductions in LRV by Iodine-V in EID confirmed the activity of EID against SARS-CoV-2 in vitro, demonstrating that Iodine-V in EID is effective at inactivating the virus in vitro and therefore suggesting its potential application intranasally to reduce SARS-CoV-2 transmission from known or suspected COVID-19 patients.
  🖺 Full Text HTML: In Vitro Efficacy of “Essential Iodine Drops” Against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2)
• How to detect and reduce potential sources of biases in epidemiologic studies of SARS-CoV-2 -
  In response to the coronavirus disease (COVID-19) pandemic, public health scientists have produced a large and rapidly expanding body of literature that aims to answer critical questions, such as the proportion of the population in a geographic area that has been infected; the transmissibility of the virus and factors associated with high infectiousness or susceptibility to infection; which groups are the most at risk of infection, morbidity and mortality; and the degree to which antibodies confer protection to re-infection. Observational studies are subject to a number of different biases, including confounding, selection bias, and measurement error, that may threaten their validity or influence the interpretation of their results. To assist in the critical evaluation of a vast body of literature and contribute to future study design, we outline and propose solutions to biases that can occur across different categories of observational studies of COVID-19. We consider potential biases that could occur in five categories of studies: (1) cross-sectional seroprevalence, (2) longitudinal seroprotection, (3) risk factor studies to inform interventions, (4) studies to estimate the secondary attack rate, and (5) studies that use secondary attack rates to make inferences about infectiousness and susceptibility.
  🖺 Full Text HTML: How to detect and reduce potential sources of biases in epidemiologic studies of SARS-CoV-2
• Increasing both specificity and sensitivity of SARS-CoV-2 antibody tests by using an adaptive orthogonal testing approach -

  Background SARS-CoV-2 antibody tests have undergone a remarkable improvement in performance. However, due to the low seroprevalence in several areas, very high demands are made on their specificity. Furthermore, the low antibody-response in some individuals requires high test sensitivity to avoid underestimating true seroprevalence. Optimization of testing has been reported through lowering manufacturer cut-offs to improve SARS-CoV-2 assay sensitivity or by combining two tests to improve specificity at the cost of sensitivity. However, these strategies have thus far been used in isolation of each other. Methods To increase sensitivity, cut-offs of three commercially available SARS-CoV-2 automated assays (Roche, Abbott, and DiaSorin) were reduced according to published values in a pre-pandemic specificity cohort (n=1117) and a SARS-CoV-2 positive cohort (n=64). All three testing systems were combined in an orthogonal approach with a confirmatory test, which was one of the remaining automated assays or one of two commercial ELISAs directed against the spike protein receptor binding-domain (RBD) or the nucleocapsid antigen (NP). Results The modified orthogonal test strategy resulted in an improved specificity of at least 99.8%, often even 100%, in all 12 tested combinations with no significant decline in sensitivity. In our cohort, regardless of whether the assays were used for screening or confirmation, combining Roche and Abbott delivered the best overall performance (+~10% sensitivity compared to the single tests and 100% specificity). Conclusion Here we propose a novel orthogonal assay strategy that approaches 100% specificity while maintaining or even significantly improving the screening test9s sensitivity.

  🖺 Full Text HTML: Increasing both specificity and sensitivity of SARS-CoV-2 antibody tests by using an adaptive orthogonal testing approach
• Excess mortality during the COVID-19 pandemic in Aden governorate, Yemen: a geospatial and statistical analysis -

  (ENGLISH) Background The burden of COVID-19 in low-income and conflict-affected countries is still unclear, largely reflecting low testing rates. In parts of Yemen, reports indicated a peak in hospital admissions and burials during May-June 2020. To estimate excess mortality during the epidemic period, we quantified activity across all identifiable cemeteries within Aden governorate in Yemen (population approximately one million) by analysing very high-resolution satellite imagery, and compared estimates to Civil Registry office records from the city. Methods After identifying active cemeteries through remote and ground information, we applied geospatial analysis techniques to manually identify new grave plots and measure changes in burial surface area over a period from July 2016 to September 2020. After imputing missing grave counts using surface area data, we used alternative approaches, including simple interpolation and a generalised additive mixed growth model, to predict both actual and counterfactual (no epidemic) burial rates by cemetery and across the governorate during the most likely period of COVID-19 excess mortality (from 1 April 2020), and thereby compute excess burials. We also analysed death notifications to the Civil Registry office during April-July 2020 and in previous years. Results We collected 78 observations from 11 cemeteries, of which 10 required imputation from burial surface area. Cemeteries ranged in starting size from 0 to 6866 graves. In all but one a peak in daily burial rates was evident from April to July 2020. Interpolation and mixed model methods estimated ≈ 1500 excess burials up to 6 July, and 2120 up to 19 September, corresponding to a peak weekly increase of 230% from the counterfactual. Satellite imagery estimates were generally lower than Civil Registry data, which indicated a peak 1823 deaths in May alone. However, both sources suggested the epidemic had waned by September 2020. Discussion To our knowledge this is the first instance of satellite imagery being used for population mortality estimation. Findings suggest a substantial, under-ascertained impact of COVID-19 in this urban Yemeni governorate, and are broadly in line with previous mathematical modelling predictions, though our method cannot distinguish direct from indirect virus deaths. Satellite imagery burial analysis appears a promising novel approach for monitoring epidemics and other crisis impacts, particularly where ground data are difficult to collect.

  🖺 Full Text HTML: Excess mortality during the COVID-19 pandemic in Aden governorate, Yemen: a geospatial and statistical analysis
• Heterogeneity in transmissibility and shedding SARS-CoV-2 via droplets and aerosols -

  Understanding the factors that mediate overdispersion in SARS-CoV-2 transmissibility is crucial towards mitigating the COVID-19 pandemic. Using a systematically developed dataset, we meta-analyze respiratory viral loads (rVLs) of SARS-CoV-2, SARS-CoV-1 and influenza A(H1N1)pdm09 from 15 countries and model infectiousness by shedding viable virus via droplets and aerosols. Our results indicate heterogeneity in rVL as an intrinsic virological factor facilitating greater overdispersion in the COVID-19 pandemic than in the 2009 H1N1 pandemic. For COVID-19, case heterogeneity remains broad throughout the infectious period, including for pediatric and asymptomatic infections. Many cases inherently present minimal transmission risk, whereas highly infectious individuals shed tens to thousands of SARS-CoV-2 virions/min via droplets and aerosols while breathing, talking and singing. Coughing increases the contagiousness, especially in close contact, of symptomatic cases relative to asymptomatic ones. Our findings show how individual case variations influence SARS-CoV-2 transmissibility and present considerations for disease control.

  🖺 Full Text HTML: Heterogeneity in transmissibility and shedding SARS-CoV-2 via droplets and aerosols
• Vaccine optimization for COVID-19, who to vaccinate first? -

  A vaccine, when available, will likely become our best tool to control the cur- rent COVID-19 pandemic. Even in the most optimistic scenarios, vaccine shortages will likely occur. Using an age-stratified mathematical model paired with optimization algorithms, we determined optimal vaccine allocation for four different metrics (deaths, symptomatic infections, and maximum non- ICU and ICU hospitalizations) under many scenarios. We find that a vaccine with effectiveness ≥50% would be enough to substantially mitigate the ongo- ing pandemic provided that a high percentage of the population is optimally vaccinated. When minimizing deaths, we find that for low vaccine effective- ness, irrespective of vaccination coverage, it is optimal to allocate vaccine to high-risk (older) age-groups first. In contrast, for higher vaccine effectiveness, there is a switch to allocate vaccine to high-transmission (younger) age-groups first for high vaccination coverage. While there are other societal and ethical considerations, this work can provide an evidence-based rationale for vaccine prioritization.

  🖺 Full Text HTML: Vaccine optimization for COVID-19, who to vaccinate first?

From Clinical Trials

• Ultramicronized Palmitoylethanolamide (PEA) Treatment in Hospitalized Participants With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: FSD201;   Drug: Placebo
  Sponsor:   FSD Pharma, Inc.
  Not yet recruiting

• Efficacy of Probiotics in Reducing Symptoms of COVID-19 - Condition:   COVID-19
  Interventions:   Dietary Supplement: Probiotics (2 strains 10x10^9 UFC);   Dietary Supplement: Placebo (potato starch and magnesium stearate)
  Sponsors:   Centre de recherche du Centre hospitalier universitaire de Sherbrooke;   Lallemand Health Solutions
  Not yet recruiting

• Safety and Immunogenicity of COVI-VAC, a Live Attenuated Vaccine Against COVID-19 - Condition:   COVID-19
  Interventions:   Biological: COVI-VAC;   Other: Placebo
  Sponsor:   Codagenix, Inc
  Not yet recruiting

• An Outpatient Study Investigating Non-prescription Treatments for COVID-19 - Condition:   COVID-19
  Interventions:   Other: chlorine dioxide;   Dietary Supplement: zinc acetate;   Drug: Famotidine;   Other: placebo;   Dietary Supplement: lactoferrin, green tea extract
  Sponsor:   Profact, Inc.
  Not yet recruiting

• A Study Evaluating the Efficacy and Safety of CKD-314 (Nafabelltan) in Hospitalized Adult Patients Diagnosed With COVID-19 Pneumonia - Condition:   COVID-19
  Intervention:   Drug: Nafamostat Mesilate
  Sponsor:   Chong Kun Dang Pharmaceutical
  Recruiting

• Angiotensin 1-7 as a Therapy in the Treatment of COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Angiotensin 1-7
  Sponsors:   Rambam Health Care Campus;   Constant Therapeutics
  Not yet recruiting

• Hyperimmune Plasma for Patients With COVID-19 - Condition:   Covid19
  Intervention:   Other: treated with hyperimmune plasma
  Sponsor:   ANNA FALANGA
  Recruiting

• Intravenous Infusion of CAP-1002 in Patients With COVID-19 - Condition:   Covid19
  Interventions:   Biological: CAP-1002;   Biological: Placebo
  Sponsor:   Capricor Inc.
  Recruiting

• Clarithromycin Versus Azithromycin in Treatment of Mild COVID-19 Infection - Condition:   Covid19
  Interventions:   Drug: Clarithromycin 500mg;   Drug: Azithromycin;   Drug: Placebo
  Sponsor:   South Valley University
  Completed

• Study of ZnAg Liquid Solution to Treat COVID-19 Symptomatic Participants - Condition:   Covid19
  Interventions:   Drug: CNM-ZnAg;   Drug: Placebo
  Sponsors:   Clene Nanomedicine;   ICL Pharma;   Azidus Brazil
  Not yet recruiting

• Efficacy and Safety of Two Hyperimmune Equine Anti Sars-CoV-2 in COVID-19 Patients - Condition:   Covid19
  Intervention:   Biological: Administration of Equine immunoglobulin anti SARS-CoV-2
  Sponsors:   Caja Costarricense de Seguro Social;   Universidad de Costa Rica;   Ministry of Health Costa Rica
  Recruiting

• Mesenchymal Stem Cells in Patients Diagnosed With COVID-19 - Condition:   Covid19
  Interventions:   Biological: MSC;   Other: Control
  Sponsors:   Hospital Reg. Lic. Adolfo Lopez Mateos;   Instituto de Terapia Celular: ITC
  Recruiting

• Diagnostic Performance Evaluation of a Novel SARS-CoV-2 (COVID-19) Antigen Detection Test - Conditions:   Covid19;   SARS-CoV-2 Infection
  Interventions:   Diagnostic Test: RT-qPCR test;   Diagnostic Test: COVID-VIRO® test
  Sponsor:   Centre Hospitalier Régional d’Orléans
  Recruiting

• plasmApuane CoV-2 : Efficacy and Safety of Immune Covid-19 Plasma in Covid-19 Pneumonia in Non ITU Patients - Condition:   Covid-19 Pneumonia
  Intervention:   Biological: immune plasma
  Sponsor:   Azienda USL Toscana Nord Ovest
  Recruiting

• Evaluation of the Efficacy of Xylitol Nasal Spray Against SARS-CoV-2 - Condition:   Covid19
  Intervention:   Drug: Nasal Spray
  Sponsors:   Larkin Community Hospital;   Ferrer Medical Innovations;   Xlear
  Recruiting

From PubMed

• Pilot study for the evaluation of safety profile of a potential inhibitor of SARS-CoV-2 endocytosis - CONCLUSIONS: We demonstrated that Endovir Stop spray is safe. The next step would be the administration of the efficacy of the spray by testing it to a wider range of people and see whether there is a reduced infection rate of SARS-CoV-2 in the treated subjects than in the non-treated individuals.

• Natural compounds as inhibitors of SARS-CoV-2 endocytosis: A promising approach against COVID-19 - CONCLUSIONS: We reviewed natural compounds with potential antiviral activity against SARS-CoV-2 that could be used as a treatment for COVID-19.

• Network Pharmacology and bioinformatics analyses identify intersection genes of niacin and COVID-19 as potential therapeutic targets - CONCLUSIONS: This study, for the first time, revealed the niacin-associated molecular functions and pharmacological targets for treating CRC/COVID-19, as COVID-19 remains a serious pandemic. But the findings were not validated in actual CRC patients infected with COVID-19, so further investigation is needed to confirm the potential use of niacin for treating CRC/COVID-19.

• Optimization and Evaluation of Propolis liposomes as a promising therapeutic approach for COVID-19 - The present work aimed to develop an optimized liposomal formulation for enhancing the anti-viral activity of propolis against COVID-19. Docking studies were performed for certain components of Egyptian Propolis using Avigan, Hydroxychloroquine and Remdesivir as standard antivirals against both COVID-19 3CL-protease and S1 spike protein. Response surface methodology and modified injection method were implemented to maximize the entrapment efficiency and release of the liposomal formulation. The…

• Inhibition of SARS-CoV-2 in Vero cell cultures by peptide-conjugated morpholino oligomers - CONCLUSIONS: The data indicate that PPMO have the ability to potently and specifically suppress SARS-CoV-2 growth and are promising candidates for further preclinical development.

• Pharmacological inhibition of acid sphingomyelinase prevents uptake of SARS-CoV-2 by epithelial cells - The acid sphingomyelinase/ceramide system plays an important role in bacterial and viral infections. Here we report that either pharmacological inhibition of acid sphingomyelinase with amitriptyline, imipramine, fluoxetine, sertraline, escitalopram, or maprotiline, or genetic downregulation of the enzyme prevents infection of cultured cells or freshy isolated human nasal epithelial cells with SARS-CoV-2 or pseudoviral pp-VSV-SARS-CoV-2 particles expressing spike, a bona fide system mimicking…

• Nanoconjugates-Based Stem Cell Therapy for the Management of COVID-19 - A potential ability of stem cells (SCs) is to regenerate and repair tissues in the human body by providing great prospects for therapeutic applications in the field of medicine. Currently, SC therapy is used in various conditions like diabetes, neurodegenerative disorders, etc. but faces some limitations like patient biocompatibility and chances of cross-infection. SCs are further modulated with nanoconjugates to overcome such challenges and will offer an advantage in the treatment of COVID-19….

• COVID-19: Is there a role for immunonutrition in obese patient? - On December 12, 2019 a new coronavirus (SARS-CoV-2) emerged in Wuhan, China, triggering a pandemic of severe acute respiratory syndrome in humans (COVID-19). Today, the scientific community is investing all the resources available to find any therapy and prevention strategies to defeat COVID-19. In this context, immunonutrition can play a pivotal role in improving immune responses against viral infections. Immunonutrition has been based on the concept that malnutrition impairs immune function….

• The Role and Therapeutic Potential of NF-kappa-B Pathway in Severe COVID-19 Patients - Coronavirus disease 2019 (COVID-19) pandemic has affected health care systems worldwide. Severe presentations of COVID-19 such as severe pneumonia and acute respiratory distress syndrome (ARDS) have been associated with the post-viral activation and release of cytokine/chemokines which leads to a “cytokine storm” causing inflammatory response and destruction, mainly affecting the lungs. COVID-19 activation of transcription factor, NF-kappa B (NF-κB) in various cells such as macrophages of lung,…

• Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection - To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a humanized decoy antibody (ACE2-Fc fusion protein) was designed to target the interaction between viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2). First, we demonstrated that ACE2-Fc could specifically abrogate virus replication by blocking the entry of SARS-CoV-2 spike-expressing pseudotyped virus into both ACE2-expressing lung cells and…

• A pharmacology-based comprehensive review on medicinal plants and phytoactive constituents possibly effective in the management of COVID-19 - Arisen in China, COVID-19 (SARS-CoV-II) is a novel coronavirus that has been expanding fast worldwide. Till now, no definite remedial drug or vaccine has been identified for COVID-19 treatment. Still, for a majority of infected patients, supportive therapy is the cornerstone of the management plan. To the importance of managing the COVID-19 pandemic, this article proposed to collecting capable medicinal plants and bioactive components in both treat and supportive therapy of this novel viral…

• Structure and inhibition of the SARS-CoV-2 main protease reveals strategy for developing dual inhibitors against M(pro) and cathepsin L - The main protease (M^(pro)) of SARS-CoV-2 is a key antiviral drug target. While most M^(pro) inhibitors have a γ-lactam glutamine surrogate at the P1 position, we recently discovered several M^(pro) inhibitors have hydrophobic moieties at the P1 site, including calpain inhibitors II and XII, which are also active against human cathepsin L, a host-protease that is important for viral entry. In this study, we solved X-ray crystal structures of M^(pro) in complex with calpain inhibitors II and XII,…

• Coevolution, Dynamics and Allostery Conspire in Shaping Cooperative Binding and Signal Transmission of the SARS-CoV-2 Spike Protein with Human Angiotensin-Converting Enzyme 2 - Binding to the host receptor is a critical initial step for the coronavirus SARS-CoV-2 spike protein to enter into target cells and trigger virus transmission. A detailed dynamic and energetic view of the binding mechanisms underlying virus entry is not fully understood and the consensus around the molecular origins behind binding preferences of SARS-CoV-2 for binding with the angiotensin-converting enzyme 2 (ACE2) host receptor is yet to be established. In this work, we performed a…

• Does eNOS derived nitric oxide protect the young from severe COVID-19 complications? - The COVID-19 pandemic poses an imminent threat to humanity, especially to the elderly. The molecular mechanisms underpinning the age-dependent disparity for disease progression is not clear. COVID-19 is both a respiratory and a vascular disease in severe patients. The damage endothelial system provides a good explanation for the various complications seen in COVID-19 patients. These observations lead us to suspect that endothelial cells are a barrier that must be breached before progression to…

• Combination therapy at an early stage of the novel coronavirus infection (COVID-19). Case series and design of the clinical trial “BromhexIne and Spironolactone for CoronvirUs Infection requiring hospiTalization (BISCUIT)” - The article focuses on effective treatment of the novel coronavirus infection (COVID-19) at early stages and substantiates the requirement for antiviral therapy and for decreasing the viral load to prevent the infection progression. The absence of a specific antiviral therapy for the SARS-CoV-2 virus is stated. The authors analyzed results of early randomized studies using lopinavir/ritonavir, remdesivir, and favipiravir in COVID-19 and their potential for the treatment of novel coronavirus…

From Patent Search

• SARS-CoV-2 예방을 위한 mRNA기반 항원보강제 혼합물 합성 방법 - 본 발명은 SARS-CoV-2(코로나 바이러스) 예방을 위한 mRNA 항원보강제에 관한 것으로 코로나 바이러스에 대한 백신으로서 상기의 항원에 대한 예방을 목적으로 하고 있다. 아이디어에는 보강제에 해당하는 완전프로인트항원보강제(CFA)와 불완전프로인트항원보강제(IFA), 번역과 안정성의 최적화가 된 mRNA, mRNA 운반체, 양이온성 지질 나노입자(lipid nanoparticles)로 구성되며 기존의 백신에 비해 효율성과 안정성의 측면에서 더 향상된 효과를 가지고 있다.

• Methods for treating Arenaviridae and Coronaviridae virus infections - Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I:

wherein the ’ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.

• Atemschutz-Baukastensystem -

  Atemschutz-Baukastensystem, das aufweist:

• eine auf zumindest Mund und Nase einer Person aufsetzbare Maske (1), die einen Eingang (11) und einen Ausgang (12) aufweist, und
• mindestens einen Schlauch (3, 31, 32),
• wobei sämtliche Komponenten des Atemschutz-Baukastensystems modular ausgebildet und über Steckverbindungen oder Schraubverbindungen (115, 125, 155, 165, 175, 215, 315, 75, 915) miteinander verbindbar sind, um der Maske (1) Luft über deren Eingang (11) zuzuführen und/oder ausgeatmete Luft vom Ausgang (12) der Maske (1) wegzuführen.

• Vorrichtung zur Übergabe und Dekontamination von mit Krankheitserregern kontaminierten Gegenständen oder Erzeugnissen -

  Vorrichtung zur Übergabe von mit Krankheitserregern kontaminierten Gegenständen oder Erzeugnissen nach einer Dekontamination, umfassend eine Einrichtung zur Dekontamination der mit Krankheitserregern kontaminierten Gegenstände oder Erzeugnisse mit mindestens einer UV-Strahlungsquelle (24), eine Durchzugseinrichtung mit Ein- und/oder Ausgabebereichen für die kontaminierten bzw. dekontaminierten Gegenstände oder Erzeugnisse, dadurch gekennzeichnet, dass die Durchzugseinrichtung im Eingang bzw. im Ausgang zum Ein- und/oder Ausgabebereich angeordnete sich paarweise gegenüberliegende Walzen (17) und Räder (4) umfasst, die zum Einzug bzw. zur Ausgabe der kontaminierten bzw. dekontaminierten Gegenstände oder Erzeugnisse vorgesehen sind, wobei die Walzen (17) und die Räder (4) durch im Ein- und/oder Ausgabebereich angeordnete Sensoren (23) und einer elektronische Kontrolleinheit (27) in Bewegung bringbar sind, wobei die Gegenstände oder Erzeugnisse in den Bereich der Einrichtung zur Dekontamination förderbar sind, der zwischen den paarweise angeordneten Walzen (17) und Rädern (4) vorgesehen ist, welcher sich gegenüberliegende Platten (25) aus Quarzglas oder einem UV-transparenten Polymermaterial, wie Graphen oder Kunstglas umfasst, über bzw. unter welchen die UV-Strahlungsquelle (24) angeordnet ist, welche als UVC-LED-Leiste und/oder Modul mit mindestens einer LED-Lampe ausgebildet ist.

• 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환의 예방 또는 치료용 조성물 - 본 발명은 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환 예방 또는 치료용 약학적 조성물을 제공한다. [화학식 1] .

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• 新型冠状病毒中和性抗体滴度检测ELISA试剂盒 - 本发明提供一种新型冠状病毒中和性抗体滴度检测ELISA试剂盒，其中包括：包被有生物素‑链霉亲和素标记的人ACE2蛋白的酶标板、辣根过氧化酶标记的新型冠状病毒RBD蛋白、新型冠状病毒中和性抗体阳性对照、包被液、洗涤液、稀释液、封闭液、显色液和终止液等。该试剂盒具有成本低，操作简单，高灵敏度、高特异性、高准确度的特点，可用于新型冠状病毒中和抗体的批量、快速检测。

• Zahnbürstenaufsatz, elektrische Versorgungseinheit einer elektrischen Zahnbürste, elektrische Zahnbürste mit einem Zahnbürstenaufsatz, Zahnbürste sowie Testaufsatz für eine elektrische Zahnbürste -

  Zahnbürstenaufsatz für eine elektrische Zahnbürste (20) umfassend einen Koppelabschnitt (2), über den der Zahnbürstenaufsatz (1) mit einer elektrischen Versorgungseinheit (10) der elektrischen Zahnbürste (20) verbindbar ist und einen Bürstenabschnitt (3), der zur Reinigung der Zähne ausgebildete Reinigungsmittel (3.1) aufweist, dadurch gekennzeichnet, dass an dem Zahnbürstenaufsatz (1) eine Sensoreinheit (4) vorgesehen ist, die dazu ausgebildet ist, selektiv das Vorhandensein eines Virus oder eines Antigen im Speichel eines Nutzers des Zahnbürstenaufsatzes (1) durch Messen zumindest eines virusspezifischen Parameters zu bestimmen.

• Wasserpfeife mit Hygienefunktion -

  Hygiene-Mundstückelement (100), aufweisend einen ersten Endabschnitt (103), welcher ausgebildet ist zur Verbindung mit einem Griff-Mundstückelement (200) einer Wasserpfeife (400) und aufweisend einen zweiten Endabschnitt (104), welcher als mundseitiges, freies Ende ausgebildet ist, wobei das Hygiene-Mundstückelement (100) ein erstes Filterelement (101) aufweist, wobei das erste Filterelement (101) wenigstens ein adsorbierendes Material umfasst und/oder wobei das Hygiene-Mundstückelement (100) ein zweites Filterelement (102) aufweist, wobei das zweite Filterelement (102) Metalloxid und/oder elektrostatisch geladene Fasern umfasst.

• 알츠하이머병 혹은 뇌졸중의 뉴로인플라마섬의 치료제로서 디디에스 혹은 그 유도체 - 목표 / 배경 :이 연구는 신경-정신과 증상을 측면과 구별하기 위해 2018 ‘NIA-AA 연구 프레임 워크’에 따라 뉴로인플라마섬 경쟁자로서 4, 4’- 디아미노디 페닐설폰(DDS, 디디에스)으로 치료받은 알츠하이머병(AD) 환자를 조사했습니다. 방법 : 서울 연구에서는 AD 진단 기준에 따라 2005 년 1 월부터 2020 년 6 월까지 보관된 소록도 국립병원 EDI 데이터베이스의 AD와 항AD약물(AAD)의 효과를 분석하여 ICD-9와 10 개의 코드를 이용하여 검색 하였습니다. 새로운 바이오마커 (D)를 사용하여 AAD로 인한 AD 증상과 신경정신병적 증상을 관리하여 수치 임상 병기를 분류했습니다. 우리는 서울 연구에서 뉴로인플라마섬 경쟁자로서 뇌경색 및 DDS 관련 사례를 보고합니다. 결과 : DDS는 DDS를 처방했거나 처방하지 않은 사람들과 AD의 비율을 비교할 때 뉴로인플라마섬 경쟁자였습니다. (D)를 도입함으로써, AD의 진행은 NCS 병기 결정을 통해 모니터링 하였습니다. AAD 또는 신경병리 증상을 구별하고 DDS로 치료했습니다. AD는 AAD에 의해 악화될 수 있고 DDS에 의해 경미한 인지 장애로 회복될 수 있습니다. 우리는 서울 연구에서 뇌경색이 발생하기 전과 후에 뉴로인플라마섬 경쟁자로서 DDS가 어떤 역할을 하는지를 임상적으로 확인했습니다. 결론 : DDS는 RBS 분할에 의한 정규/비정규적 우비퀴틴화, NLRP3 inflammasome 형성, Higgins의 캐스케이드 및 철이 풍부한 강자성 나노 입자를 차단하는 역할을 합니다. 바이오마커 (D)를 통하여 DDS로 AD를 예방하고 치료할 수 있습니다. AD에 대한 예방 및 치료 방법으로 뉴로인플라마섬을 치료하는 것을 수치 임상 병기(NCS, Numeric clinical staging)를 통하여 증명하고 있습니다.

• A electronic biometric system - An electronic biometric system, the system comprising:

• a biometric detection means arranged to:

• detect at least one biological characteristic of a person