Covid-19 Sentry

Contents

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

From Preprints

• Knowledge graphs and wikidata subsetting -
  Knowledge graphs have successfully been adopted by academia, governement and industry to represent large scale knowledge bases. Open and collaborative knowledge graphs such as Wikidata capture knowledge from different domains and harmonize them under a common format, making it easier for researchers to access the data while also supporting Open Science. Wikidata keeps getting bigger and better, which subsumes integration use cases. Having a large amount of data such as the one presented in a scopeless Wikidata offers some advantages, e.g., unique access point and common format, but also poses some challenges, e.g., performance. Regular wikidata users are not unfamiliar with running into frequent timeouts of submitted queries. Due to its popularity, limits have been imposed to allow for fair access to many. However this suppreses many interesting and complex queries that require more computational power and resources. Replicating Wikidata on one’s own infrastructure can be a solution which also offers a snapshot of the contents of wikidata at some given point in time. There is no need to replicate Wikidata in full, it is possible to work with subsets targeting, for instance, a particular domain. Creating those subsets has emerged as an alternative to reduce the amount and spectrum of data offered by Wikidata. Less data makes more complex queries possible while still keeping the compatibility with the whole Wikidata as the model is kept. In this paper we report the tasks done as part of a Wikidata subsetting project during the Virtual BioHackathon Europe 2020 and SWAT4(HC)LS 2021, which had already started at NBDC/DBCLS BioHackathon 2019 in Japan, SWAT4(HC)LS hackathon 2019, and Virtual COVID-19 BioHackathon 2019. We describe some of approaches we identified to create subsets and some susbsets from the Life Sciences domain as well as other use cases we also discussed.
  🖺 Full Text HTML: Knowledge graphs and wikidata subsetting
• Factor Analysis Approach to Classify COVID-19 Datasets in Several Regions -
  The aim of this research is to investigate the relationship between the counts of cases with Covid-19 and the deaths due to it in seven countries that are severely affected by the pandemic. First, the Pearson’s correlation is used to determine the relationships among these countries. Then, the factor analysis is applied to categorize these countries based on their relationships.
  🖺 Full Text HTML: Factor Analysis Approach to Classify COVID-19 Datasets in Several Regions
• Analysis of glycosylation and disulfide bonding of wild-type SARS-CoV-2 spike glycoprotein -
  The SARS-CoV-2 coronavirus, the etiologic agent of COVID-19, uses its spike (S) glycoprotein anchored in the viral membrane to enter host cells. The S glycoprotein is the major target for neutralizing antibodies elicited by natural infection and by vaccines. Approximately 35% of the SARS-CoV-2 S glycoprotein consists of carbohydrate, which can influence virus infectivity and susceptibility to antibody inhibition. We found that virus-like particles produced by coexpression of SARS-CoV-2 S, M, E and N proteins contained spike glycoproteins that were extensively modified by complex carbohydrates. We used a fucose-selective lectin to enrich the Golgi-resident fraction of a wild-type SARS-CoV-2 S glycoprotein trimer, and determined its glycosylation and disulfide bond profile. Compared with soluble or solubilized S glycoproteins modified to prevent proteolytic cleavage and to retain a prefusion conformation, more of the wild-type S glycoprotein N-linked glycans are processed to complex forms. Even Asn 234, a significant percentage of which is decorated by high-mannose glycans on soluble and virion S trimers, is predominantly modified in the Golgi by processed glycans. Three incompletely occupied sites of O-linked glycosylation were detected. Viruses pseudotyped with natural variants of the serine/threonine residues implicated in O-linked glycosylation were generally infectious and exhibited sensitivity to neutralization by soluble ACE2 and convalescent antisera comparable to that of the wild-type virus. Unlike other natural cysteine variants, a Cys15Phe (C15F) mutant retained partial, but unstable, infectivity. These findings enhance our understanding of the Golgi processing of the native SARS-CoV-2 S glycoprotein carbohydrates and could assist the design of interventions.
  🖺 Full Text HTML: Analysis of glycosylation and disulfide bonding of wild-type SARS-CoV-2 spike glycoprotein
• SARS-CoV-2 binding to ACE2 triggers pericyte-mediated angiotensin-evoked cerebral capillary constriction -
  The SARS-CoV-2 receptor, ACE2, is found on pericytes, contractile cells enwrapping capillaries that regulate brain, heart and kidney blood flow. ACE2 converts vasoconstricting angiotensin II into vasodilating angiotensin-(1-7). In brain slices from hamster, which has an ACE2 sequence similar to human ACE2, angiotensin II alone evoked only a small capillary constriction, but evoked a large pericyte-mediated capillary constriction generated by AT1 receptors in the presence of the SARS-CoV-2 receptor binding domain (RBD). The effect of the RBD was mimicked by blocking ACE2. A mutated non-binding RBD did not potentiate constriction. A similar RBD-potentiated capillary constriction occurred in human cortical slices. This constriction reflects an RBD-induced decrease in the conversion of angiotensin II to angiotensin-(1-7). The clinically-used drug losartan inhibited the RBD-potentiated constriction. Thus AT1 receptor blockers could be protective in SARS-CoV-2 infection by reducing pericyte-mediated blood flow reductions in the brain, and perhaps the heart and kidney.
  🖺 Full Text HTML: SARS-CoV-2 binding to ACE2 triggers pericyte-mediated angiotensin-evoked cerebral capillary constriction
• Identification of lectin receptors for conserved SARS-CoV-2 glycosylation sites -
  New SARS-CoV-2 variants are continuously emerging with critical implications for therapies or vaccinations. All 22 N-glycan sites of SARS-CoV-2 Spike remain highly conserved among the variants B.1.1.7, 501Y.V2 and P.1, opening an avenue for robust therapeutic intervention. Here we used a comprehensive library of mammalian carbohydrate-binding proteins (lectins) to probe critical sugar residues on the full-length trimeric Spike and the receptor binding domain (RBD) of SARS-CoV-2. Two lectins, Clec4g and CD209c, were identified to strongly bind to Spike. Clec4g and CD209c binding to Spike was dissected and visualized in real time and at single molecule resolution using atomic force microscopy. 3D modelling showed that both lectins can bind to a glycan within the RBD-ACE2 interface and thus interferes with Spike binding to cell surfaces. Importantly, Clec4g and CD209c significantly reduced SARS-CoV-2 infections. These data report the first extensive map and 3D structural modelling of lectin-Spike interactions and uncovers candidate receptors involved in Spike binding and SARS-CoV-2 infections. The capacity of CLEC4G and mCD209c lectins to block SARS-CoV-2 viral entry holds promise for pan-variant therapeutic interventions.
  🖺 Full Text HTML: Identification of lectin receptors for conserved SARS-CoV-2 glycosylation sites
• Ultrapotent bispecific antibodies neutralize emerging SARS-CoV-2 variants -
  The emergence of SARS-CoV-2 variants that threaten the efficacy of existing vaccines and therapeutic antibodies underscores the urgent need for new antibody-based tools that potently neutralize variants by targeting multiple sites of the spike protein. We isolated 216 monoclonal antibodies targeting SARS-CoV-2 from plasmablasts and memory B cells of COVID-19 patients. The three most potent antibodies targeted distinct regions of the RBD, and all three neutralized the SARS-CoV-2 variants B.1.1.7 and B.1.351. The crystal structure of the most potent antibody, CV503, revealed that it binds to the ridge region of SARS-CoV-2 RBD, competes with the ACE2 receptor, and has limited contact with key variant residues K417, E484 and N501. We designed bispecific antibodies by combining non-overlapping specificities and identified five ultrapotent bispecific antibodies that inhibit authentic SARS-CoV-2 infection at concentrations of <1 ng/mL. Through a novel mode of action three bispecific antibodies cross-linked adjacent spike proteins using dual NTD/RBD specificities. One bispecific antibody was >100-fold more potent than a cocktail of its parent monoclonals in vitro and prevented clinical disease in a hamster model at a 2.5 mg/kg dose. Notably, six of nine bispecific antibodies neutralized B.1.1.7, B.1.351 and the wild-type virus with comparable potency, despite partial or complete loss of activity of at least one parent monoclonal antibody against B.1.351. Furthermore, a bispecific antibody that neutralized B.1.351 protected against SARS-CoV-2 expressing the crucial E484K mutation in the hamster model. Thus, bispecific antibodies represent a promising next-generation countermeasure against SARS-CoV-2 variants of concern.
  🖺 Full Text HTML: Ultrapotent bispecific antibodies neutralize emerging SARS-CoV-2 variants
• Psychological distress and resilience in a sample of Adolescents and Young Adults with cancer during the COVID-19 pandemic -

  BACKGROUND: Adolescents and young people (AYA) with cancer are at greater risk of psychological distress which can impact treatment. COVID-19 has resulted in changes to cancer care delivery and AYA have been disproportionately affected by economic and educational effects of COVID-19, potentially impacting on mental health. Understanding the impact of COVID-19 on AYA with cancer is important to inform care. METHODS: Online survey of 16-24 year olds receiving cancer treatment at 8 cancer centres in the UK in December 2020. We measured: self-perceived increased anxiety since COVID-19, impact of COVID-19 on treatment, life and relationships and used the 8-item Patient Health Questionnaire(PHQ-8), 7-item Generalised Anxiety Disorder Scale(GAD) and the 2-item Connor-Davidson Resilience Scale(CD-RISC). RESULTS: 112 AYA participated (17.8% of total eligible). 62.8% were female, 67.3% were 21-24 years. 83% were white. 59.8% had previously experienced mental health difficulties. 67.9% received cancer treatment during the pandemic and 33.9% were diagnosed during the pandemic. 78.6% reported COVID-19 having a significant impact on their life, 55.4% on their key relationship and 39.3% on their treatment. 79% reported experiencing some degree of increased anxiety since COVID-19.43.4% had moderate-severe PHQ-8 scores and 37.1% for GADS-7. Self-report of impact on life was associated with greater anxiety during COVID-19 and moderate-severe PHQ-8 score (OR 3.64, 95% CI 2.52 to 19.40, p <0.01; OR 5.23, 95%CI 1.65 to 16.56, p < 0.01). Impact on relationships was associated with greater anxiety and moderate-severe GADS-7and PHQ-8 score (OR 2.89, 95% CI 1.11 to 7.54, p = 0,03; OR 3.54, 95% CI 2.32 to 15.17, p<0.01; OR 2.42, 95% CI 1.11 to 5.25, p =0.03). Greater CD-RISC score was associated with lower risk of anxiety and mod-severe GADS-7and PHQ-8 scores (OR 0.58, 95%CI 0.41 to 0.81, p <0.01; OR 0.55 95% CI 0.4 to 0.72, p <0.01; OR 0.52, 95% CI 0.38 to 0.69, p <0.01) CONCLUSIONS: We found high levels of psychological distress in AYA with cancer, which is important knowledge for clinical teams working with this age group. Perceived impact of COVID-19 on relationships and life was predictive of poorer mental health, with resilience a potential protective factor.

  🖺 Full Text HTML: Psychological distress and resilience in a sample of Adolescents and Young Adults with cancer during the COVID-19 pandemic
• How unequal vaccine distribution promotes the evolution of vaccine escape -

  Health officials warn that SARS-CoV-2 vaccines must be uniformly distributed within and among countries if we are to quell the ongoing pandemic. Yet there has been little critical assessment of the underlying reasons for this warning. Here, we explicitly show why vaccine equity is necessary. Perhaps counter-intuitively, we find that vaccine escape mutants are less likely to come from highly vaccinated regions where there is strong selection pressure favoring vaccine escape and more likely to come from neighboring unvaccinated regions where there is no selection favoring escape. Unvaccinated geographic regions thus provide evolutionary reservoirs from which new strains can arise and cause new epidemics within neighboring vaccinated regions and beyond. Our findings have timely implications for vaccine rollout strategies and public health policy.

  🖺 Full Text HTML: How unequal vaccine distribution promotes the evolution of vaccine escape
• Proteomic and Metabolomic Investigation of COVID-19 Patients with Elevated Serum Lactate Dehydrogenase -

  Serum lactate dehydrogenase (LDH) has been established as a prognostic indicator given its differential expression in COVID-19 patients. However, the molecular mechanisms underneath remain poorly understood. In this study, 144 COVID-19 patients were enrolled to monitor the clinical and laboratory parameters over three weeks. Serum lactate dehydrogenase (LDH) was shown elevated in the COVID-19 patients on admission and declined during the convalescence period, and its ability to classify patient severity outperformed other clinical indicators. A threshold of 247 U/L serum LDH on admission was determined for severity prognosis. Next, we classified a subset of 14 patients into high- and low-risk groups based on serum LDH expression and compared their quantitative serum proteomic and metabolomic differences. The results found COVID-19 patients with high serum LDH exhibited differentially expressed blood coagulation and immune responses including acute inflammatory responses, platelet degranulation, complement cascade, as well as multiple different metabolic responses including lipid metabolism, protein ubiquitination and pyruvate fermentation. Specifically, activation of hypoxia responses was highlighted in patients with high LDH expressions. Taken together, our data showed that serum LDH levels is associated COVID-19 severity, and that elevated serum LDH might be consequences of hypoxia and tissue injuries induced by inflammation.

  🖺 Full Text HTML: Proteomic and Metabolomic Investigation of COVID-19 Patients with Elevated Serum Lactate Dehydrogenase
• A network modelling approach to assess non-pharmaceutical disease controls in a worker population: An application to SARS-CoV-2 -

  Background: As part of a concerted pandemic response to protect public health, businesses can enact non-pharmaceutical controls to minimise exposure to pathogens in workplaces and premises open to the public. Amendments to working practices can lead to the amount, duration and/or proximity of interactions being changed, ultimately altering the dynamics of disease spread. These modifications could be specific to the type of business being operated. Methods: We use a data-driven approach to parameterise an individual-based network model for transmission of SARS-CoV-2 amongst the working population, stratified into work sectors. The network is comprised of layered contacts to consider the risk of spread in multiple encounter settings (workplaces, households, social and other). We analyse several interventions targeted towards working practices: mandating a fraction of the population to work from home; using temporally asynchronous work patterns; and introducing measures to create 9COVID-secure9 workplaces. We also assess the general role of adherence to (or effectiveness of) isolation and test and trace measures and demonstrate the impact of all these interventions across a variety of relevant metrics. Results: The progress of the epidemic can be significantly hindered by instructing a significant proportion of the workforce to work from home. Furthermore, if required to be present at the workplace, asynchronous work patterns can help to reduce infections when compared with scenarios where all workers work on the same days, particularly for longer working weeks. When assessing COVID-secure workplace measures, we found that smaller work teams and a greater reduction in transmission risk reduced the probability of large, prolonged outbreaks. Finally, following isolation guidance and engaging with contact tracing without other measures is an effective tool to curb transmission, but is highly sensitive to adherence levels. Conclusions: In the absence of sufficient adherence to non-pharmaceutical interventions, our results indicate a high likelihood of SARS-CoV-2 spreading widely throughout a worker population. Given the heterogeneity of demographic attributes across worker roles, in addition to the individual nature of controls such as contact tracing, we demonstrate the utility of a network model approach to investigate workplace-targeted intervention strategies and the role of test, trace and isolation in tackling disease spread.

  🖺 Full Text HTML: A network modelling approach to assess non-pharmaceutical disease controls in a worker population: An application to SARS-CoV-2
• Hydrogel-based slow release of a receptor-binding domain subunit vaccine elicits neutralizing antibody responses against SARS-CoV-2 -
  The development of an effective vaccine that can be rapidly manufactured and distributed worldwide is necessary to mitigate the devastating health and economic impacts of pandemics like COVID-19. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, which mediates host cell entry of the virus, is an appealing antigen for subunit vaccines because it is easy to manufacture and highly stable. Moreover, RBD is a target for neutralizing antibodies and robust cytotoxic T lymphocyte responses. Unfortunately, RBD is poorly immunogenic. While most subunit vaccines are commonly formulated with adjuvants to enhance their immunogenicity, most common adjuvant combinations have not been sufficient to improve RBD immunogenicity and none have afforded neutralizing responses in a single-dose RBD vaccine. Here we show that sustained delivery of an RBD subunit vaccine in an injectable hydrogel depot formulation increases total anti-RBD IgG titers compared to bolus administration of the same vaccines. Notably, a SARS-CoV-2 spike-pseudotyped lentivirus neutralization assay revealed neutralizing antibodies in all mice after a single hydrogel vaccine administration comprising clinically-approved adjuvants Alum and CpG. Together, these results suggest that extending the exposure to RBD subunit vaccines significantly enhances the immunogenicity of RBD and induces neutralizing humoral immunity following a single immunization.
  🖺 Full Text HTML: Hydrogel-based slow release of a receptor-binding domain subunit vaccine elicits neutralizing antibody responses against SARS-CoV-2
• The need for accessibility to chloride to solubilize insoluble salts may underlie some cases of hypertension -
  Hypertension is the greatest risk factor for stroke. It is the most common comorbidity of COVID-19, and may be partly caused by the widespread distribution of insoluble and stiff calcium salts such as calcium oxalate. As an intrinsic defensive mechanism, tissues in hypertensive individuals increase blood pressure to pump NaCl to inaccessible parts of the body, and chloride, as a strong anion can solubilize insoluble and rigid salts which are stressful to cells.
  🖺 Full Text HTML: The need for accessibility to chloride to solubilize insoluble salts may underlie some cases of hypertension
• An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces sterile immunity and prevents transmission of SARS-CoV-2 between cats -
  Early in the global SARS-CoV-2 pandemic concerns were raised regarding infection of other animal hosts and whether these could play a significant role in the viral epidemiology. Infection of animals could be detrimental by causing clinical disease but also of concern if they become a viral reservoir allowing further mutations, plus having the potential to infect other animals or humans. The first reported animals to be infected both under experimental conditions and from anecdotal field evidence were cats described in China early in 2020. Given the concerns this finding raised and the close contacts between humans and cats, we aimed to determine whether a vaccine candidate could be developed that was suitable for use in multiple susceptible animal species and whether this vaccine could reduce infection of cats in addition to preventing spread to other cats. Here we report that a Replicon Particle (RP) vaccine based on Venezuelan equine encephalitis virus (VEEV), known to be safe and efficacious for use in a variety of animals, expressing a stabilised Spike antigen, could induce neutralising antibody titers in guinea pigs and cats. After two intramuscular vaccinations, virus neutralising antibodies were detected in the respiratory tract of the guinea pigs and a cell mediated immune response was induced. The design of the SARS-CoV-2 antigen was shown to be critical in developing a strong neutralising antibody response. Vaccination of cats was able to induce a serum neutralising antibody response which lasted for the course of the experiment. Interestingly, in contrast to control animals, infectious virus could not be detected in oropharyngeal or nasal swabs of vaccinated cats after challenge. Moreover, the challenged control cats spread the virus to in-contact cats whereas the vaccinated cats did not transmit virus. The results show that the RP vaccine induces sterile immunity preventing SARS-CoV-2 infection and transmission. This data suggests that this RP vaccine could be a multi-species vaccine useful for preventing spread to and between other animals should that approach be required.
  🖺 Full Text HTML: An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces sterile immunity and prevents transmission of SARS-CoV-2 between cats
• Coagulation factors directly cleave SARS-CoV-2 spike and enhance viral entry -
  Coagulopathy is recognized as a significant aspect of morbidity in COVID-19 patients. The clotting cascade is propagated by a series of proteases, including factor Xa and thrombin. Other host proteases, including TMPRSS2, are recognized to be important for cleavage activation of SARS-CoV-2 spike to promote viral entry. Using biochemical and cell-based assays, we demonstrate that factor Xa and thrombin can also directly cleave SARS-CoV-2 spike, enhancing viral entry. A drug-repurposing screen identified a subset of protease inhibitors that promiscuously inhibited spike cleavage by both transmembrane serine proteases as well as coagulation factors. The mechanism of the protease inhibitors nafamostat and camostat extend beyond inhibition of TMPRSS2 to coagulation-induced spike cleavage. Anticoagulation is critical in the management of COVID-19, and early intervention could provide collateral benefit by suppressing SARS-CoV-2 viral entry. We propose a model of positive feedback whereby infection-induced hypercoagulation exacerbates SARS-CoV-2 infectivity.
  🖺 Full Text HTML: Coagulation factors directly cleave SARS-CoV-2 spike and enhance viral entry
• Limiting the priming dose of a SARS CoV-2 vaccine improves virus-specific immunity -
  Since late 2019, SARS-CoV-2 has caused a global pandemic that has infected 128 million people worldwide. Although several vaccine candidates have received emergency use authorization (EUA), there are still a limited number of vaccine doses available. To increase the number of vaccinated individuals, there are ongoing discussions about administering partial vaccine doses, but there is still a paucity of data on how vaccine fractionation affects vaccine-elicited immunity. We performed studies in mice to understand how the priming dose of a SARS CoV-2 vaccine affects long-term immunity to SARS CoV-2. We first primed C57BL/6 mice with an adenovirus-based vaccine encoding SARS CoV-2 spike protein (Ad5-SARS-2 spike), similar to that used in the CanSino and Sputnik V vaccines. This prime was administered either at a low dose (LD) of 106 PFU or at a standard dose (SD) of 109 PFU, followed by a SD boost in all mice four weeks later. As expected, the LD prime induced lower immune responses relative to the SD prime. However, the LD prime elicited immune responses that were qualitatively superior, and upon boosting, mice that were initially primed with a LD exhibited significantly more potent immune responses. Overall, these data demonstrate that limiting the priming dose of a SARS CoV-2 vaccine may confer unexpected benefits. These findings may be useful for improving vaccine availability and for rational vaccine design.
  🖺 Full Text HTML: Limiting the priming dose of a SARS CoV-2 vaccine improves virus-specific immunity

From Clinical Trials

• Pilot Trial of XFBD, a TCM, in Persons With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Xuanfei Baidu Granules;   Other: Placebo
  Sponsor:   Darcy Spicer
  Recruiting

• SERUR: COVID-19 Serological Survey of Staff From the University Reims-Champagne Ardennes - Condition:   Covid19
  Intervention:   Diagnostic Test: Anti-SARS-CoV2 Serology
  Sponsor:   Université de Reims Champagne-Ardenne
  Completed

• Study of DS-5670a (COVID-19 Vaccine) in Japanese Healthy Adults and Elderly Subjects - Condition:   Covid19
  Interventions:   Biological: DS-5670a;   Biological: Placebo
  Sponsor:   Daiichi Sankyo Co., Ltd.
  Recruiting

• ANTIcoagulation in Severe COVID-19 Patients - Condition:   Severe COVID-19 Pneumonia
  Interventions:   Drug: Tinzaparin, Low dose prophylactic anticoagulation;   Drug: Tinzaparin, High dose prophylactic anticoagulation;   Drug: Tinzaparin,Therapeutic anticoagulation
  Sponsor:   Assistance Publique - Hôpitaux de Paris
  Not yet recruiting

• Neuromodulation in COVID-19 Patients - Condition:   COVID-19
  Interventions:   Device: Transcranial direct-current stimulation;   Device: Sham Transcranial direct-current stimulation
  Sponsors:   D’Or Institute for Research and Education;   Rio de Janeiro State Research Supporting Foundation (FAPERJ);   Conselho Nacional de Desenvolvimento Científico e Tecnológico;   Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
  Not yet recruiting

• A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Elderly Adults - Condition:   Covid19 Vaccine
  Interventions:   Biological: MVC-COV1901 (High-Dose);   Biological: MVC-COV1901(Mid-Dose)
  Sponsor:   Medigen Vaccine Biologics Corp.
  Not yet recruiting

• Immunogenicity and Safety of Recombinant COVID-19 Vaccine (CHO Cells) - Condition:   COVID-19
  Interventions:   Biological: a middle-dose recombinant COVID-19 vaccine (CHO Cell) (18-59 years) at the schedule of day 0, 28, 56;   Biological: a high-dose recombinant COVID-19 vaccine (CHO Cell) (18-59 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose recombinant COVID-19 vaccine (CHO Cell) (60-85 years) at the schedule of day 0, 28, 56;   Biological: a high-dose recombinant COVID-19 vaccine (CHO Cell) (60-85 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose placebo (18-59 years) at the schedule of day 0, 28, 56;   Biological: a high-dose placebo (18-59 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose placebo (60-85 years) at the schedule of day 0, 28, 56;   Biological: a high-dose placebo (60-85 years) at the schedule of day 0, 28, 56
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   Academy of Military Medical Sciences，Academy of Military Sciences，PLA ZHONGYIANKE Biotech Co, Ltd. LIAONINGMAOKANGYUAN Biotech Co, Ltd
  Recruiting

• Efficacy, Immunogenicity and Safety of Inactivated ERUCOV-VAC Compared With Placebo in COVID-19 - Condition:   COVID-19
  Interventions:   Biological: ERUCOV-VAC 3 µg/0.5 ml Vaccine;   Biological: ERUCOV-VAC 6 µg/0.5 ml Vaccine;   Other: Placebo
  Sponsors:   Health Institutes of Turkey;   Erciyes University Scientific Research Projects Coordination
  Recruiting

• Post COVID-19 Syndrome and the Gut-lung Axis - Condition:   Covid19
  Interventions:   Dietary Supplement: Omni-Biotic Pro Vi 5;   Dietary Supplement: Placebo
  Sponsors:   Medical University of Graz;   CBmed Ges.m.b.H.
  Not yet recruiting

• A Dose Finding, Efficacy and Safety Study of Ensovibep (MP0420) in Ambulatory Adult Patients With Symptomatic COVID-19 - Condition:   COVID-19
  Interventions:   Drug: ensovibep;   Drug: Placebo
  Sponsors:   Molecular Partners AG;   Novartis Pharmaceuticals;   Iqvia Pty Ltd;   Datamap;   SYNLAB Analytics & Services Switzerland AG;   Q2 Solutions
  Not yet recruiting

• Vitamin D, Omega-3, and Combination Vitamins B, C and Zinc Supplementation for the Treatment and Prevention of COVID-19 - Condition:   Covid19
  Interventions:   Dietary Supplement: Vitamin D;   Dietary Supplement: Omega DHA / EPA;   Dietary Supplement: Vitamin C, Vitamin B complex and Zinc Acetate
  Sponsors:   Hospital de la Soledad;   Microclinic International
  Recruiting

• The Impact of Fecal Microbiota Transplantation as an Immunomodulation on the Risk Reduction of COVID-19 Disease Progression With Escalating Cytokine Storm and Inflammatory Parameters - Condition:   Covid19
  Interventions:   Drug: Human fecal microbiota, MBiotix HBI;   Drug: Placebo;   Drug: SOC
  Sponsors:   Medical University of Warsaw;   Human Biome Institute, Poland
  Not yet recruiting

• STOP-COVID19: Superiority Trial Of Protease Inhibition in COVID-19 - Condition:   Covid19
  Interventions:   Drug: Brensocatib;   Drug: Placebo
  Sponsors:   University of Dundee;   NHS Tayside;   Insmed Incorporated
  Completed

• Monitoring of COVID-19 Seroprevalence Among GHdC Staff Members - Condition:   Covid19
  Intervention:   Diagnostic Test: Serology to determine SARS-CoV-2 infection
  Sponsor:   Grand Hôpital de Charleroi
  Recruiting

• Favipiravir in High-risk COVID-19 Patients - Condition:   Covid19
  Intervention:   Drug: Favipiravir
  Sponsor:   Penang Hospital, Malaysia
  Recruiting

From PubMed

• A review on antiviral and immunomodulatory polysaccharides from Indian medicinal plants, which may be beneficial to COVID-19 infected patients - The emergence of the novel coronavirus, SARS-CoV-2 has pushed forward the world to experience the first pandemic of this century. Any specific drug against this RNA virus is yet to be discovered and presently, the COVID-19 infected patients are being treated symptomatically. During the last few decades, a number of polysaccharides with potential biological activities have been invented from Indian medicinal plants. Many polysaccharides, such as sulfated xylomannan, xylan, pectins, fucoidans,…

• SARS-CoV2 Nsp16 activation mechanism and a cryptic pocket with pan-coronavirus antiviral potential - Coronaviruses have caused multiple epidemics in the past two decades, in addition to the current COVID-19 pandemic that is severely damaging global health and the economy. Coronaviruses employ between twenty and thirty proteins to carry out their viral replication cycle including infection, immune evasion, and replication. Among these, nonstructural protein 16 (Nsp16), a 2’-O-methyltransferase, plays an essential role in immune evasion. Nsp16 achieves this by mimicking its human homolog, CMTr1,…

• SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies - The global spread of SARS-CoV-2/COVID-19 is devastating health systems and economies worldwide. Recombinant or vaccine-induced neutralizing antibodies are used to combat the COVID-19 pandemic. However, the recently emerged SARS-CoV-2 variants B.1.1.7 (UK), B.1.351 (South Africa), and P.1 (Brazil) harbor mutations in the viral spike (S) protein that may alter virus-host cell interactions and confer resistance to inhibitors and antibodies. Here, using pseudoparticles, we show that entry of all…

• Weak humoral immune reactivity among residents of long-term care facilities following one dose of the BNT162b2 mRNA COVID-19 vaccine - BACKGROUND: Several Canadian provinces are extending the interval between COVID-19 vaccine doses to increase population vaccine coverage more rapidly. However, immunogenicity of these vaccines after one dose is incompletely characterized, particularly among the elderly, who are at greatest risk of severe COVID-19.

• Transcriptome and Functions of Granulocytic Myeloid-Derived Suppressor Cells Determine their Association with Disease Severity of COVID-19 - COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19, that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of Granulocytic-MDSC (G-MDSC) may in part explain…

• Sulforaphane exhibits in vitro and in vivo antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are no orally available medications for prophylaxis for those exposed to SARS-CoV-2 and limited therapeutic options for those who develop COVID-19. We evaluated the antiviral activity of sulforaphane (SFN), a naturally occurring, orally available, well-tolerated, nutritional supplement present in high concentrations in cruciferous…

• TMPRSS2 inhibitor discovery facilitated through an in silico and biochemical screening platform - The COVID-19 pandemic has highlighted the need for new antiviral targets, as many of the currently approved drugs have proven ineffective against mitigating SARS-CoV-2 infections. The host transmembrane serine protease TMPRSS2 is a highly promising antiviral target, as it plays a direct role in priming the spike protein before viral entry occurs. Further, unlike other targets such as ACE2, TMPRSS2 has no known biological role. Here we utilize virtual screening to curate large libraries into a…

• The Prolyl-tRNA Synthetase Inhibitor Halofuginone Inhibits SARS-CoV-2 Infection - We identify the prolyl-tRNA synthetase (PRS) inhibitor halofuginone ¹ , a compound in clinical trials for anti-fibrotic and anti-inflammatory applications ² , as a potent inhibitor of SARS-CoV-2 infection and replication. The interaction of SARS-CoV-2 spike protein with cell surface heparan sulfate (HS) promotes viral entry ³ . We find that halofuginone reduces HS biosynthesis, thereby reducing spike protein binding, SARS-CoV-2 pseudotyped virus, and authentic SARS-CoV-2 infection. Halofuginone…

• BTK inhibitors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Systematic Review - ImportanceThe Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against lethal influenza-induced acute lung injury in mice. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe coronavirus disease 2019 (COVID-19). ObjectiveTo evaluate the use of BTK inhibitors (BTKinibs) during COVID-19 and assess how they may affect patient outcomes.Evidence ReviewWe searched…

• Tocilizumab: An Effective Therapy for Severely and Critically Ill COVID-19 Patients - Background: Tocilizumab (TCZ), a monoclonal antibody against the most prevalent cytokine interleukin-6 (IL-6), is an emerging therapeutic option for COVID-19 infections. The present study was undertaken to assess the therapeutic response of TCZ therapy in severely or critically ill COVID-19 patients and its role as an effective modality of management. Methods: The present retrospective observational study included 30 admitted severely or critically ill COVID-19 patients, treated with TCZ therapy…

• Computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir - Outcomes of various clinical studies for the coronavirus disease 2019 (COVID-19) treatment indicated that the drug acts via inhibition of multiple pathways (targets) is likely to be more successful and promising. Keeping this hypothesis intact, the present study describes for the first-time, Grazoprevir, an FDA approved anti-viral drug primarily approved for Hepatitis C Virus (HCV), mediated multiple pathway control via synergistic inhibition of viral entry targeting host cell…

• Activation of STING signaling pathway effectively blocks human coronavirus infection - The COVID-19 pandemic poses a serious global health threat. The rapid global spread of SARS-CoV-2 highlights an urgent need to develop effective therapeutics for blocking SARS-CoV-2 infection and spread. Stimulator of Interferon Genes (STING) is a chief element in host antiviral defense pathways. In this study, we examined the impact of the STING signaling pathway on coronavirus infection using the HCoV-OC43 model. We found that HCoV-OC43 infection did not stimulate the STING signaling pathway,…

• Antiviral Drug Ivermectin at Nanomolar Concentrations Inhibits Glycine-Induced Chloride Current in Rat Hippocampal Neurons - Ivermectin (IVM) belongs to the class of macrocyclic lactones, which is used as an antiparasitic agent. At present, the researchers focus on possibility to use IVM in treatment of certain forms of cancer and viral diseases such as COVID-19. The mechanisms of IVM action are not clear. It is assumed that IVM affects chloride channels and increases cytoplasmic concentration of chloride. This study examines the effect of IVM on chloride currents induced by glycine (I(Gly)). Experiments were carried…

• A Clinical-Stage Cysteine Protease Inhibitor blocks SARS-CoV-2 Infection of Human and Monkey Cells - Host-cell cysteine proteases play an essential role in the processing of the viral spike protein of SARS coronaviruses. K777, an irreversible, covalent inactivator of cysteine proteases that has recently completed phase 1 clinical trials, reduced SARS-CoV-2 viral infectivity in several host cells: Vero E6 (EC(50)< 74 nM), HeLa/ACE2 (4 nM), Caco-2 (EC(90) = 4.3 μM), and A549/ACE2 (<80 nM). Infectivity of Calu-3 cells depended on the cell line assayed. If Calu-3/2B4 was used, EC(50) was 7 nM, but…

• Novel Compounds Targeting Neuropilin Receptor 1 with Potential To Interfere with SARS-CoV-2 Virus Entry - Neuropilin-1 (NRP-1) is a multifunctional transmembrane receptor for ligands that affect developmental axonal growth and angiogenesis. In addition to a role in cancer, NRP-1 is a reported entry point for several viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19). The furin cleavage product of SARS-CoV-2 Spike protein takes advantage of the vascular endothelial growth factor A (VEGF-A) binding site on NRP-1…

From Patent Search

• 5-(4-TERT-BUTOXY PHENYL)-3-(4N-OCTYLOXYPHENYL)-4,5-DIHYDROISOXAZOLE MOLECULE (C-I): A PROMISING DRUG FOR SARS-COV-2 (TARGET I) AND BLOOD CANCER (TARGET II) - The present invention relates to a method ofmolecular docking of crystalline compound (C-I) with SARS-COV 2 proteins and its repurposing with proteins of blood cancer, comprising the steps of ; employing an algorithmto carry molecular docking calculations of the crystalized compound (C-I); studying the compound computationally to understand the effect of binding groups with the atoms of the amino acids on at least four target proteins of SARS-COV 2; downloading the structure of the proteins; removing water molecules, co enzymes and inhibitors attached to the enzymes; drawing the structure using Chem Sketch software; converting the mol file into a PDB file; using crystalized compound (C-I) for comparative and drug repurposing with two other mutated proteins; docking compound into the groove of the proteins; saving format of docked molecules retrieved; and filtering and docking the best docked results. - link

• USING CLINICAL ONTOLOGIES TO BUILD KNOWLEDGE BASED CLINICAL DECISION SUPPORT SYSTEM FOR NOVEL CORONAVIRUS (COVID-19) WITH THE ADOPTION OF TELECONFERENCING FOR THE PRIMARY HEALTH CENTRES/SATELLITE CLINICS OF ROYAL OMAN POLICE IN SULTANATE OF OMAN - - link

• Peptides and their use in diagnosis of SARS-CoV-2 infection - - link

• A PROCESS FOR SUCCESSFUL MANAGEMENT OF COVID 19 POSITIVE PATIENTS - - link

• IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2 - IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2Insilico screening of antimycobacterial natural compounds with the potential to directly inhibit SARS COV2 relates to the composition for treating SARS-COV-2 comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. The composition also treats treating SARS, Ebola, Hepatitis-B and Hepatitis–C comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. - link

• Sars-CoV-2 vaccine antigens - - link

• SARS-COV-2 BINDING PROTEINS - - link

• Bildschirmgerät mit verbesserter Wirkung bei der Befestigung von UV-Entkeimungslampen -

  Ein Bildschirmgerät mit verbesserter Wirkung bei der Befestigung von UV-Entkeimungslampen, umfassend: ein Bildschirmgerät, das einen Umfang hat; eine UV-Entkeimungslampe, die sich am Umfang des Bildschirmgeräts befindet; eine Stromquelle, die elektrisch mit der UV-Entkeimungslampe verbunden ist; eine Steuerschaltung, die elektrisch mit der UV-Entkeimungslampe verbunden ist; und eine Befestigungsvorrichtung, durch die die UV-Entkeimungslampe am Umfang des Bildschirmgeräts befestigbar ist, wobei die Befestigungsvorrichtung einen Sitzkörper, eine erste Klemmplatte und eine zweite Klemmplatte aufweist, wobei der Sitzkörper mit der UV-Entkeimungslampe versehen ist, wobei die erste Klemmplatte und die zweite Klemmplatte beabstandet am Sitzkörper gleitbar angeordnet sind, wodurch ein Klemmabstand zwischen der ersten Klemmplatte und der zweiten Klemmplatte besteht, wobei ein elastisches Element zwischen der zweiten Klemmplatte und dem Sitzkörper angeordnet ist, um die zweite Klemmplatte dazu zu zwingen, sich der ersten Klemmplatte zu nähern.

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• Schublade mit antiepidemischer Wirkung -

  Schublade mit antiepidemischer Wirkung, mit einem Schrank (1); mindestens einer Schublade (2), die in dem Schrank (1) angeordnet ist, wobei jede Schublade (2) einen Schubladenraum (25) aufweist; einer UV-Sterilisationsvorrichtung (3), die an der Schublade (2) angeordnet ist; einer Stromquelle (4), die elektrisch mit der UV-Sterilisationsvorrichtung (3) verbunden ist; einer Steuerschaltung (5), die elektrisch mit der Stromquelle (4) und der UV-Sterilisationsvorrichtung (3) verbunden ist; und einem Sensor (6), der elektrisch mit der Steuerschaltung (5) verbunden ist.

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• Gerät zur Unterstützung und Verstärkung natürlicher Lüftung -

  Lüftungssystem für einen mit öffnbaren Fenstern (16) ausgestatteten Gebäuderaum, gekennzeichnet dadurch, dass es ein Gehäuse (18) und einen Ventilator (20) aufweist, wobei durch das Gehäuse eine vom Ventilator erzeugte Luftströmung strömen kann, wobei das Gehäuse dafür eine Einströmöffnung (24) für Luft und eine Ausströmöffnung (22) für Luft enthält, wobei eine der beiden Öffnungen der Form eines Öffnungsspalts (26) zwischen einem Fensterflügel (12) und einem Blendrahmen (14) des Fensters (16) angepasst ist.

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