Covid-19 Sentry

Contents

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

From Preprints

• Commentary The Elderly in the pandemic era -
  Highlighted manuscript Dapsone has been the treatment and preventive drug for mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, Seizure, Stroke and Covid-19 ARDS. B.K.’s team at Hunt Regional Hospital reported a study that drastically reduced mortality by administering Dapsone to patients with Covid-19 ARDS in the intensive care unit. If Dapsone were used for early symptoms of cognitive impairment or stroke, the increase in deaths would have been prevented. J.H. also recommends it to the elderly living in this pandemic era. However, we must consult our doctor before taking it.
  🖺 Full Text HTML: Commentary The Elderly in the pandemic era
• A Multicenter Evaluation of Blood Purification with Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19: A Preliminary Report -

  Objective: The Seraph 100 Microbind Affinity Blood Filter (Seraph 100) is an extracorporeal medical countermeasure that can remove many pathogens from blood, including the SARS-CoV-2 virus. The aim of this study was to evaluate safety and efficacy of Seraph 100 treatment for severe coronavirus 2019 disease (COVID-19). Design: Multicenter retrospective observational cohort study. Setting: Intensive care units across four of thirteen participating sites who have completed data extraction. Patients: Critically ill COVID-19 patients treated with Seraph 100 under an Emergency Use Authorization (n=53) and historical control patients who met criteria for treatment (n=46). Intervention: Extracorporeal treatment with the Seraph 100 filter. Measurements and Main Results: At baseline, the median age was 61 years, 72.7% were male, and 59.6% required mechanical ventilation. The groups were matched in terms of sex, race/ethnicity, body mass index, APACHE II score, need for mechanical ventilation, and other COVID-19 treatments. However, patients in the Seraph 100 group were younger with a median age of 61 years (IQR 42-65) compared to controls who had a median age of 64 (IQR 56-68, p=0.036). The Seraph 100 group also had a lower median Charlson comorbidity index (2, IQR 0-3) compared to control patients (3, IQR 2-4, p=0.006). Mortality was lower in the Seraph 100 treated group compared to the historical controls (37.7% vs 67.4%, respectively, p=0.003). Multivariable logistic regression analysis yielded an odds ratio of 0.27 (95% confidence interval 0.09-0.79, p=0.016). Of the 53 patients treated with Seraph 100, only 1 patient experienced a serious adverse event (transient hypotension at the start of the treatment which required a brief period of vasopressor support). Conclusions: These data suggest that broad spectrum, pathogen agnostic, extracorporeal blood purification technologies can be safely deployed to meet new pathogen threats as an adjunct to standard treatments and can mitigate against poor outcomes while awaiting the development of directed pharmacologic therapies and/or vaccines.

  🖺 Full Text HTML: A Multicenter Evaluation of Blood Purification with Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19: A Preliminary Report
• Systematic review of the association between ABO blood type and COVID-19 incidence and mortality -

  A large proportion of COVID-19 research has been focused on identifying markers of high-risk individuals. However, this research often fails to consider basic epidemiologic concepts to prevent bias in the design, selection, and analysis of observational data. One suspected marker of risk that has been repeatedly assessed is ABO blood type. Given the ease of measuring this biomarker, it is an appealing target for identifying high-risk individuals. However, this same ease of measurement makes associational research on ABO blood type and COVID prone to a range of common epidemiologic errors. We conducted a systematic review of studies assessing correlations between ABO blood type and COVID incidence, hospitalization, and mortality to determine the quality of evidence these studies provide and whether the overall evidence suggests ABO blood type could provide a useful indicator of COVID risk. We conclude that most existing studies are low quality and suffer from major methodological flaws. The few higher-quality studies which do exist find no association between ABO blood type and COVID outcomes. We conclude that there is no evidence to support the use of ABO blood type as a marker for COVID risk or severity.

  🖺 Full Text HTML: Systematic review of the association between ABO blood type and COVID-19 incidence and mortality
• Frequency of neurological manifestations in COVID-19: a systematic review and meta-analysis of 350 studies -

  Objective: To summarize the frequency of neurological manifestations reported in COVID-19 patients and investigate the association of these manifestations with disease severity and mortality. Design: Systematic review and meta-analysis Eligibility criteria: Studies enrolling consecutive COVID-19 patients (probable or confirmed) presenting with neurological manifestations. Data sources: PubMed, Medline, Cochrane library, clinicaltrials.gov and EMBASE from 31st December 2019 to 15th December 2020. Data extraction and analysis: Two authors independently screened titles and abstracts retrieved by literature search. Risk of bias was examined using Joanna Briggs Institute (JBI) scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% Confidence Intervals (CI) were calculated for neurological manifestations. Odds ratio (OR) and 95%CI were calculated to determine the association of neurological manifestations with disease severity and mortality. Presence of heterogeneity was assessed using I-square, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2. Results: Of 2,455 citations, 350 studies were included in this review, providing data on 145,634 COVID-19 patients, 89% of whom were hospitalized. Forty-one neurological manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurological symptoms included: fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%) and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurological diagnosis (pooled prevalence- 2%). In COVID-19 patients aged >60, the pooled prevalence of acute confusion/delirium was 34% and the presence of any neurological manifestations in this age group was associated with mortality (OR 1.80; 95%CI 1.11 to 2.91). Conclusions: Up to one-third of COVID-19 patients analysed in this review experienced at least one neurological manifestation. One in 50 patients experienced stroke. In those over 60, more than one-third had acute confusion/delirium; the presence of neurological manifestations in this group was associated with near doubling of mortality. Results must be interpreted keeping in view the limitations of observational studies and associated bias.

  🖺 Full Text HTML: Frequency of neurological manifestations in COVID-19: a systematic review and meta-analysis of 350 studies
• The Great Deceiver: miR-2392’s Hidden Role in Driving SARS-CoV-2 Infection -
  MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we have discovered a circulating miRNA, miR-2392, that is directly involved with SARS-CoV-2 machinery during host infection. Specifically, we found that miR-2392 was key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia as well as promoting many symptoms associated with COVID-19 infection. We demonstrate miR-2392 is present in the blood and urine of COVID-19 patients tested, but not detected in COVID-19 negative patients. These findings indicate the potential for developing a novel, minimally invasive, COVID-19 detection method. Lastly, using both in vitro human and in vivo hamster models, we have developed a novel miRNA-based antiviral therapeutic targeting miR-2392 that significantly reduces SARS-CoV-2 viability and may potentially inhibit a COVID-19 disease state in the host.
  🖺 Full Text HTML: The Great Deceiver: miR-2392’s Hidden Role in Driving SARS-CoV-2 Infection
• Inactivation of SARS-CoV-2 by β-propiolactone Causes Aggregation of Viral Particles and Loss of Antigenic Potential -
  Inactivated viral preparations are important resources in vaccine and antisera industry. Of the many vaccines that are being developed against COVID-19, inactivated whole-virus vaccines are also considered effective. {beta}-propiolactone (BPL) is a widely used chemical inactivator of several viruses. Here, we analyze various concentrations of BPL to effectively inactivate SARS-CoV-2 and their effects on the biochemical properties of the virion particles. BPL at 1:2000 (v/v) concentrations effectively inactivated SARS-CoV-2. However, higher BPL concentrations resulted in the loss of both protein content as well as the antigenic integrity of the structural proteins. Higher concentrations also caused substantial aggregation of the virion particles possibly causing undesirable outcomes including a potential immune escape by infectious virions, and a loss in antigenic potential. We also identify that the viral RNA content in the culture supernatants can be a direct indicator of their antigenic content. Our findings may have important implications in the vaccine and antisera industry during COVID-19 pandemic.
  🖺 Full Text HTML: Inactivation of SARS-CoV-2 by β-propiolactone Causes Aggregation of Viral Particles and Loss of Antigenic Potential
• Gut microbiota diversity and C-Reactive Protein are predictors of disease severity in COVID-19 patients -
  Risk factors for COVID-19 disease severity are still poorly understood. Considering the pivotal role of gut microbiota on host immune and inflammatory functions, we investigated the association between changes in gut microbiota composition and the clinical severity of COVID-19. We conducted a multicentre cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: 1) WHO Clinical Progression Scale - mild 19 (16.5%), moderate 37 (32.2%) or severe 59 (51.3%); and 2) location of recovery from COVID-19 - ambulatory 14 (household isolation; 12.2%), hospitalized in ward 40 (34.8%) or intensive care unit 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing and data obtained was further related with clinical parameters of COVID-19 patients. Risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models. In comparison with mild COVID-19 patients, the gut microbiota of moderate and severe patients has: a) lower Firmicutes/Bacteroidetes ratio, b) higher abundance of Proteobacteria; and c) lower abundance of beneficial butyrate-producing bacteria such as Roseburia and Lachnospira genera. Multivariable regression analysis showed that Shannon index diversity (odds ratio [OR] 2.85 [95% CI 1.09-7.41]; p=0.032) and C-Reactive Protein (OR 3.45 [95% CI 1.33-8.91]; p=0.011) were risk factors for COVID-19 severe disease (a score of 6 or higher in WHO clinical progression scale). In conclusion, our results demonstrated that hospitalised moderate and severe COVID-19 patients have microbial signatures of gut dysbiosis and for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker for COVID-19 disease severity.
  🖺 Full Text HTML: Gut microbiota diversity and C-Reactive Protein are predictors of disease severity in COVID-19 patients
• Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection -
  SARS-CoV-2 can cause a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of the host factors mediating viral infection or restriction is critical to elucidate SARS-CoV-2 host-pathogen interactions and the progression of COVID-19. To this end, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. These screens uncovered proviral and antiviral host factors across highly interconnected host pathways, including components implicated in clathrin transport, inflammatory signaling, cell cycle regulation, and transcriptional and epigenetic regulation. Mucins, a family of high-molecular weight glycoproteins and the main constituent of mucus, are central components of a prominent viral restriction pathway that we identified. We demonstrate that multiple membrane-anchored mucins are critical inhibitors of SARS-CoV-2 entry and are upregulated in response to viral infection. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and suggests interactions between SARS-CoV-2 and airway mucins of COVID-19 patients as a host defense mechanism.
  🖺 Full Text HTML: Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection
• Prefusion conformation of SARS-CoV-2 receptor-binding domain favors interactions with human receptor ACE2 -
  A new coronavirus epidemic COVID-19 caused by Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) poses serious threat across continents, leading to the World Health Organization declaration of a Public Health Emergence of International Concern. In order to stop the entry of the virus into human host cell, major therapeutic and vaccine design efforts are now targeting interactions between the SARS-CoV-2 spike (S) glycoprotein and the human cellular membrane receptor angiotensin-converting enzyme, hACE2. By analysing cryo-EM structures of SARS-CoV-2 and SARS-CoV-1, we report here that the homotrimer SARS-CoV-2 S receptor-binding domain (RBD) that bind with hACE2 has expanded in size with a large conformational change of its AA residues relative to SARS-CoV-1 S protein. Protomer with the up-conformational form RBD that only can bind with hACE2 showed higher intermolecular interactions at the interface, with differential distributions and the inclusion of two specific H-bonds in the CoV-2 complex. However, these interactions are resulted in significant reductions in structural rigidity, favouring proteolytic processing of S protein for the fusion of the viral and cellular membrane. Further conformational dynamics analysis of the RBD motions of SARS-CoV-2 and SARS-CoV-1 point to the role in modification in the RBD conformational dynamics and their likely impact on infectivity.
  🖺 Full Text HTML: Prefusion conformation of SARS-CoV-2 receptor-binding domain favors interactions with human receptor ACE2
• Resolutive results with oral corticosteroids for patients with COVID-19 in pulmonary inflammatory phase. Successful outpatient experience during the collapse of Belem do Para Health System - Brazil. -

  In the face of new diseases, medicine needs to reinvent itself in order to contain and control epidemics, such as the one we have recently faced, COVID-19, a disease with a wide spectrum of clinical severity. A new moment has been established, since the application of well known, effective and safe medications for other diseases, has shown high success rates in the treatment of COVID-19. Thereunto, studies with early intervention are needed, which can change the unfavorable outcome of patients. In this article, we report the successful experience using an oral strategy during the collapse of Belem do Para Health System, Brazil. Two hundred and ten patients were diagnosed with respiratory failure due to COVID-19, with no option of hospital treatment due to lack of beds and resources. These patients were then started on therapeutic regimen consisting of prednisolone, enoxaparin and macrolides associated and followed in outpatient facilities. Two hundred and eight patients had excellent therapeutic response and there were only two fatalities. These results push research boundaries, valuing outpatient treatment with early use of prednisolone in the initial pulmonary phase, preventing severe COVID-19 pneumonitis. Adoption of the proposed treatment intends to reduce the need for hospitalization, as well as lethality, with social robust benefits and incalculable economic savings since involves the use of accessible, safe and not expensive medications.

  🖺 Full Text HTML: Resolutive results with oral corticosteroids for patients with COVID-19 in pulmonary inflammatory phase. Successful outpatient experience during the collapse of Belem do Para Health System - Brazil.
• Topical TMPRSS2 inhibition prevents SARS-CoV-2 infection in differentiated primary human airway cells -
  Background: There are no effective prophylactic treatments for SARS-CoV-2 infection, and limited early treatment options. Viral cell entry requires spike protein binding to the ACE2 receptor and spike cleavage by TMPRSS2, a cell surface serine protease. Targeting of TMPRSS2 by either androgen blockade or direct inhibition is already in clinical trials in early SARS-CoV-2 infection. Methods: The likely initial cells of SARS-CoV-2 entry are the ciliated cells of the upper airway. We therefore used differentiated primary human airway epithelial cells maintained at the air-liquid interface (ALI) to test the impact of targeting TMPRSS2 on the prevention of SARS-CoV-2 infection. Results: We first modelled the systemic delivery of compounds. Enzalutamide, an oral androgen receptor antagonist, had no impact on SARS-Cov-2 infection. By contrast, camostat mesylate, an orally available serine protease inhibitor, blocked SARS-CoV-2 entry. However, camostat is rapidly metabolised in the circulation in vivo, and systemic bioavailability after oral dosing is low. We therefore modelled local airway administration by applying camostat to the apical surface of the differentiated ALI cultures. We demonstrated that a brief exposure to topical camostat is effective at restricting SARS-CoV-2 viral infection. Conclusion: These experiments demonstrate a potential therapeutic role for topical camostat for pre- or post-exposure prophylaxis of SARS-CoV-2, which can now be evaluated in a clinical trial.
  🖺 Full Text HTML: Topical TMPRSS2 inhibition prevents SARS-CoV-2 infection in differentiated primary human airway cells
• Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees -
  The drastic rise in the number of cases in Maharashtra, India has created a matter of concern for public health experts. Twelve isolates of VUI lineage B.1.617 were propagated in VeroCCL81 cells and characterized. Convalescent sera of the COVID-19 cases and recipients of BBV152 (Covaxin) were able to neutralize VUI B.1.617.
  🖺 Full Text HTML: Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees
• Large-scale analysis of synonymous viral variants reveals global adaptation of the SARS-CoV-2 to the human codon usage -
  Many large national and transnational studies were dedicated to the analysis of SARS-CoV-2 genome. Most studies are focused on missense and nonsense mutations, however approximately 30% of the SARS-CoV-2 variants are synonymous, therefore changing the target codon without affecting the corresponding protein sequence. Here, by performing a large-scale analysis of more than 40000 SARS-CoV-2 genome sequences, we show that, over time, the virus is adapting its codon usage to that of the human host through the accumulation of silent mutations, thus likely improving its effectiveness in using the human aminoacyl-tRNA set. The sole exception to this rule is represented by mutations bearing the signature of the defensive APOlipoprotein B Editing Complex (APOBEC) machinery, which show a negative profile. Taken globally, this study indicates that codon usage adaptation may play a relevant role in the evolution of SARS-CoV-2, which appears to be much more complex than previously anticipated.
  🖺 Full Text HTML: Large-scale analysis of synonymous viral variants reveals global adaptation of the SARS-CoV-2 to the human codon usage
• Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate -
  A main clinical parameter of COVID-19 pathophysiology is hypoxia. Here we show that hypoxia decreases the attachment of the receptor binding domain (RBD) and the S1 subunit (S1) of the spike protein to epithelial cells. In Vero E6 cells, hypoxia reduces the protein levels of ACE2 and neuropilin-1 (NRP1), which might in part explain the observed reduction of the infection rate. In addition, hypoxia inhibits the binding of the spike to NCI-H460 human lung epithelial cells by decreasing the cell surface levels of heparan sulfate (HS), a known attachment receptor of SARS-CoV-2. This interaction is also reduced by lactoferrin, a glycoprotein that blocks HS moieties on the cell surface. The expression of syndecan-1, an HS-containing proteoglycan expressed in lung, is inhibited by hypoxia on a HIF-1-dependent manner. Hypoxia or deletion of syndecan-1 results in reduced binding of the RBD to host cells. Our study indicates that hypoxia acts to prevent SARS-CoV-2 infection, suggesting that the hypoxia signaling pathway might offer therapeutic opportunities for the treatment of COVID-19.
  🖺 Full Text HTML: Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate
• Persistence of SARS-CoV-2 virus and viral RNA on hydrophobic and hydrophilic surfaces and investigating contamination concentration -
  The transmission of SARS-CoV-2 is likely to occur through a number of routes, including contact with contaminated surfaces. Many studies have used RT-PCR analysis to detect SARS-CoV-2 RNA on surfaces but seldom has viable virus been detected. This paper investigates the viability over time of SARS-CoV-2 dried onto a range of materials and compares viability of the virus to RNA copies recovered, and whether virus viability is concentration dependant. Viable virus persisted for the longest time on surgical mask material and stainless steel with a 99.9% reduction in viability by 124 and 113 hours respectively. Viability of SARS-CoV-2 reduced the fastest on a polyester shirt, with a 99.9% reduction within 2.5 hours. Viability on cotton was reduced second fastest, with 99.9% reduction in 72 hours. RNA on all the surfaces exhibited a one log reduction in genome copy recovery over 21 days. The findings show that SARS-CoV-2 is most stable on non-porous hydrophobic surfaces. RNA is highly stable when dried on surfaces with only one log reduction in recovery over three weeks. In comparison, SARS-CoV-2 viability reduced more rapidly, but this loss in viability was found to be independent of starting concentration. Expected levels of SARS-CoV-2 viable environmental surface contamination would lead to undetectable levels within two days. Therefore, when RNA is detected on surfaces it does not directly indicate presence of viable virus even at high CT values.
  🖺 Full Text HTML: Persistence of SARS-CoV-2 virus and viral RNA on hydrophobic and hydrophilic surfaces and investigating contamination concentration

From Clinical Trials

• Oestrogen Treatment for COVID-19 Symptoms - Condition:   COVID-19
  Intervention:   Drug: Transdermal estradiol gel
  Sponsors:   Hamad Medical Corporation;   Laboratoires Besins International
  Not yet recruiting

• Virgin Coconut Oil as Adjunctive Therapy for Hospitalized COVID-19 Patients - Condition:   Covid19
  Intervention:   Drug: Virgin Coconut Oil
  Sponsors:   University of the Philippines;   Philippine Coconut Authority;   Philippine Council for Health Research & Development
  Recruiting

• Study to Evaluate a Single Dose of LTX-109 in Subjects With COVID-19 Infection. - Condition:   COVID-19
  Interventions:   Drug: LTX-109 gel, 3%;   Drug: Placebo gel
  Sponsors:   Pharma Holdings AS;   Clinical Trial Consultants AB
  Not yet recruiting

• Clinical Study in the Treatment of Patients With Moderate Course of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: COVID-globulin;   Drug: Placebo
  Sponsor:   Microgen
  Recruiting

• Safety and Immunogenicity of Demi-dose of Two Covid-19 mRNA Vaccines in Healthy Population - Condition:   Covid19
  Intervention:   Diagnostic Test: immunogenicity after first and second dose
  Sponsors:   Sciensano;   Mensura EDPB;   Institute of Tropical Medicine, Belgium;   Erasme University Hospital
  Not yet recruiting

• A Clinical Study Evaluating Inhaled Aviptadil on COVID-19 - Condition:   Covid19
  Interventions:   Drug: Inhaled Aviptadil;   Drug: Placebo
  Sponsors:   Centurion Pharma;   Klinar CRO
  Recruiting

• The Effects of a Multi-factorial Rehabilitation Program for Healthcare Workers Suffering From Post-COVID-19 Fatigue Syndrome - Condition:   COVID-19
  Intervention:   Other: Exercise
  Sponsor:   Medical University of Vienna
  Recruiting

• ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19 - Condition:   Covid19
  Interventions:   Biological: Remdesivir;   Drug: Remdesivir Placebo;   Biological: Aviptadil;   Drug: Aviptadil Placebo;   Drug: Corticosteroid
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   NeuroRx, Inc.;   Gilead Sciences
  Recruiting

• COVID-19 Close Contact Self-Testing Study - Condition:   Covid19
  Interventions:   Behavioral: COVID-19 self-test;   Behavioral: COVID-19 test referral
  Sponsor:   University of Pennsylvania
  Not yet recruiting

• Total-Body Parametric 18F-FDG PET of COVID-19 - Condition:   Covid19
  Intervention:   Device: uEXPLORER/mCT
  Sponsor:   University of California, Davis
  Recruiting

• Lactoferrin in Covid-19 Hospitalized Patients - Condition:   Covid19
  Interventions:   Dietary Supplement: Bovine lactoferrin;   Dietary Supplement: Placebo administration
  Sponsor:   Paolo Manzoni
  Recruiting

• Remdesivir Efficacy In Management Of COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: Remdesivir;   Drug: Standard of care_1;   Drug: Standard of care_2
  Sponsor:   Ain Shams University
  Completed

• SLV213 Treatment in COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: SLV213;   Drug: Placebo
  Sponsors:   Kenneth Krantz, MD, PhD;   FHI Clinical, Inc.
  Not yet recruiting

• Evaluation of Anti-COVID 19 Pfizer Vaccination Effect on COVID 19 Detection Using Breath Analysis - Condition:   Covid19
  Intervention:   Diagnostic Test: vaccination against COVID19
  Sponsor:   Scentech Medical Technologies Ltd
  Recruiting

• Nebulized Heparin for COVID19-associated Acute Respiratory Failure - Condition:   Covid19
  Interventions:   Drug: Heparin;   Drug: Placebo
  Sponsor:   University of Kentucky
  Recruiting

From PubMed

• Expedited Approach toward the Rational Design of Noncovalent SARS-CoV-2 Main Protease Inhibitors - The main protease (M^(pro)) of SARS-CoV-2 is a validated antiviral drug target. Several M^(pro) inhibitors have been reported with potent enzymatic inhibition and cellular antiviral activity, including GC376, boceprevir, calpain inhibitors II, and XII, with each containing a reactive warhead that covalently modifies the catalytic Cys145. Coupling structure-based drug design with the one-pot Ugi four-component reaction, we discovered one of the most potent noncovalent inhibitors, 23R (Jun8-76-3A)…

• Structural Basis of Potential Inhibitors Targeting SARS-CoV-2 Main Protease - The Coronavirus disease-19 (COVID-19) pandemic is still devastating the world causing significant social, economic, and political chaos. Corresponding to the absence of globally approved antiviral drugs for treatment and vaccines for controlling the pandemic, the number of cases and/or mortalities are still rising. Current patient management relies on supportive treatment and the use of repurposed drugs as an indispensable option. Of a crucial role in the viral life cycle, ongoing studies are…

• Prediction of Anti-COVID 19 Therapeutic Power of Medicinal Moroccan Plants Using Molecular Docking - The emerging pathogen SARS-CoV2 causing coronavirus disease 2019 (COVID-19) is a global public health challenge. To the present day, COVID-19 had affected more than 40 million people worldwide. The exploration and the development of new bioactive compounds with cost-effective and specific anti-COVID 19 therapeutic power is the prime focus of the current medical research. Thus, the exploitation of the molecular docking technique has become essential in the discovery and development of new drugs,…

• Nanoparticle composite TPNT1 is effective against SARS-CoV-2 and influenza viruses - A metal nanoparticle composite, namely TPNT1, which contains Au-NP (1 ppm), Ag-NP (5 ppm), ZnO-NP (60 ppm) and ClO(2) (42.5 ppm) in aqueous solution was prepared and characterized by spectroscopy, transmission electron microscopy, dynamic light scattering analysis and potentiometric titration. Based on the in vitro cell-based assay, TPNT1 inhibited six major clades of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with effective concentration within the range to be used as food…

• SARS-CoV-2 can recruit a haem metabolite to evade antibody immunity - The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARS-CoV-2 spike binds biliverdin and bilirubin, the tetrapyrrole products of haem metabolism, with nanomolar affinity. Using cryo-electron microscopy and X-ray crystallography, we mapped the tetrapyrrole interaction pocket to a deep cleft on the spike N-terminal domain (NTD). At physiological concentrations, biliverdin significantly dampened the reactivity of SARS-CoV-2 spike with immune…

• Development of ciclesonide analogues that block SARS-CoV-2 RNA replication - Ciclesonide is an inhaled corticosteroid used to treat asthma and is currently undergoing clinical trials for treatment of coronavirus disease 2019 (COVID-19). An active metabolite of ciclesonide, Cic2, was recently reported to repress severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomic RNA replication. Herein, we designed and synthesized a few types of ciclesonide analogues. Cic4 (bearing an azide group) and Cic6 (bearing a chloro group) potently decreased SARS-CoV-2 viral…

• Potent Toxic Effects of Taroxaz-104 on the Replication of SARS-CoV-2 Particles - Polyphenolics and 1,3,4-oxadiazoles are two of the most potent bioactive classes of compounds in medicinal chemistry, since both are known for their diverse pharmacological activities in humans. One of their prominent activities is the antimicrobial/antiviral activities, which are much apparent when the key functional structural moieties of both of them meet into the same compounds. The current COVID-19 pandemic motivated us to computationally screen and evaluate our library of…

• Binding of the SARS-CoV-2 Spike Protein to the Asialoglycoprotein Receptor on Human Primary Hepatocytes and Immortalized Hepatocyte-Like Cells by Confocal Analysis - CONCLUSION: The absence of ACE-2 receptors and inhibition of spike binding by an antibody to the ASGr1 on both PHH and HLC suggested that the spike protein interacts with the ASGr1. The differential antibody blocking of spike binding to AT2, PHH and HLC indicated that neutralizing activity of SARS-CoV-2 binding might involve additional mechanisms beyond RBD binding to ACE-2.

• Antiviral peptides from aquatic organisms: Functionality and potential inhibitory effect on SARS-CoV-2 - Several antiviral peptides (AVPs) from aquatic organisms have been effective in interfering with the actions of infectious viruses, such as Human Immunodeficiency Virus-1 and Herpes Simplex Virus-1 and 2. AVPs are able to block viral attachment or entry into host cells, inhibit internal fusion or replication events by suppressing viral gene transcription, and prevent viral infections by modulating host immunity. Therefore, as promising therapeutics, the potential of aquatic AVPs for use against…

• Potential Candidates against COVID-19 Targeting RNA-Dependent RNA Polymerase: A Comprehensive Review - Due to the extremely contagious nature of SARS-COV-2, it presents a significant threat to humans worldwide. A plethora of studies are going on all over the world to discover the drug to fight SARS-COV-2. One of the most promising targets is RNA-dependent RNA polymerase (RdRp), responsible for viral RNA replication in host cells. Since RdRp is a viral enzyme with no host cell homologs, it allows the development of selective SARS-COV-2 RdRp inhibitors. A variety of studies used in silico…

• Immunopharmacological perspective on zinc in SARS-CoV-2 infection - The novel SARS-CoV-2 which was first reported in China is the cause of infection known as COVID-19. In comparison with other coronaviruses such as SARS-CoV and MERS, the mortality rate of SARS-CoV-2 is lower but the transmissibility is higher. Immune dysregulation is the most common feature of the immunopathogenesis of COVID-19 that leads to hyperinflammation. Micronutrients such as zinc are essential for normal immune function. According to the assessment of WHO, approximately one-third of the…

• An international, interlaboratory ring trial confirms the feasibility of an open-source, extraction-less “direct” RT-qPCR method for reliable detection of SARS-CoV-2 RNA in clinical samples - Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is used worldwide to test and trace the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). “Extraction-less” or “direct” real time-reverse transcription polymerase chain reaction (RT-PCR) is an open-access qualitative method for SARS-CoV-2 detection from nasopharyngeal or oral pharyngeal samples with the potential to generate actionable data more quickly, at a lower cost, and with fewer experimental…

• Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2 - Infection by SARS-CoV-2 generally causes mild symptoms but can lead to severe disease and death in certain populations, including the immunocompromised. Drug repurposing efforts are underway to identify compounds that interfere with SARS-CoV-2 replication or the immunopathology it can elicit. Rapamycin is among those being currently tested in clinical trials for impacts on COVID-19 severity. While rapamycin and rapamycin analogs (rapalogs) are FDA-approved for use as mTOR inhibitors in multiple…

• CRISPR/Cas-New Molecular Scissors in Diagnostics and Therapeutics of COVID-19 - The current pandemic of COVID-19, with its climbing number of cases and deaths, has us searching for tools for rapid, reliable, and affordable methods of detection on one hand, and novel, improved therapeutic strategies on the other. The currently employed RT-PCR method, despite its all-encompassing utility, has its shortcomings. Newer diagnostic tools, based on the Clustered Regularly Interspaced Short Palindromic Repeats/Cas(CRISPR-Cas) system, with its better diagnostic accuracy measures,…

• Structurally modified compounds of hydroxychloroquine, remdesivir and tetrahydrocannabinol against main protease of SARS-CoV-2, a possible hope for COVID-19: Docking and Molecular Dynamics Simulation studies - Now a days, more than 200 countries faces the health crisis due to epidemiological disease COVID-19 caused by SARS-CoV-2 virus. It will cause a very high impact on world’s economy and global health sector. Earlier the structure of main protease (M^(pro)) protein was deposited in the RCSB protein repository. Hydroxychloroquine (HCQ) and remdesivir were found to effective in treatment of COVID-19 patients. Here we have performed docking and molecule dynamic (MD) simulation study of HCQ and…

From Patent Search

• Compositions and methods for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection - - link

• 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

• AQUEOUS ZINC OXIDE NANOSPRAY COMPOSITIONS - Disclosed herein is aqueous zinc oxide nano spray compositions comprising zinc oxide nanoparticles and a synthetic surfactant for controlling the spread of Covid-19 virus. - link

• Bettverlängerungssystem -

  Bettverlängerungssystem (1) für in Bauchlage beatmungspflichtige Patienten in Gestalt mit zumindest einer Platte (16), dadurch gekennzeichnet, dass die Platte (16) im Kopflagerungsbereich einen Luftwegezugangsdurchbruch (8) mit einem den Luftwegezugangsdurchbruch (8) umgebenden Auflagerbereich für ein durchbrochenes Kopfauflagepolster (14) aufweist, durch den von der Bettunterseite her und durch das Kopfauflagepolster (14) hindurch die Ver- und Entsorgungsschläuche für eine orotracheale Intubation oder eine nasotracheale Intubation ventral an das Gesicht des Patienten herangeführt werden können, und dass die Platte (16) im Bereich ihrer dem Kopfende eines Bettrosts (15) zugeordneten Stirnseite (6) ein Fixierelement (2) zur Befestigung der Platte (16) am Bettrost (15) nach Art eines einseitig frei über das Kopfende des Bettrosts hinausragenden Kragträgers aufweist.

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• 一种肝素类药物组合物、喷鼻剂及其制备方法及应用 - 本发明公开了一种肝素类药物组合物、喷鼻剂及其制备方法及应用。该肝素类药物组合物包括肝素钠和阿比朵尔。本发明中的肝素类药物组合物首次采用肝素钠和阿比朵尔联合使用，普通肝素钠联合1μM/L以上的阿比朵尔病毒抑制效率显著高于单独普通肝素钠或单独阿比多尔组（p<0.05）。 - 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

• 抗SARS-COV-2中和抗体 - 本公开提供了针对SARS‑COV‑2的新颖中和抗体和其抗原结合片段。还提供了包括其的药物组合物和试剂盒以及其用途。 - link

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

• Luftdesinfektionssäule -

  Luftreinigungssäule (1) mit einer Luftaufnahme (2) und einer Luftausgabe (3), wobei zwischen der Luftaufnahme (2) und der Luftausgabe (3) ein luftleitender Bereich (4) mit einem Gebläse (7) und einer UV-Lichtdesinfektionseinrichtung (5) angeordnet ist, dadurch gekennzeichnet, dass der luftleitende Bereich (4) photokathalysatorisch beschichtete Oberflächen (9) aufweist und/oder ein photokathalysatorisch beschichtetes Gitter (11) angeordnet ist, wobei photokathalysatorisch beschichtetes Gitter (11) und die photokathalysatorisch beschichtete Oberflächen (9) mit Titandioxid (TiO₂) beschichtet sind, wobei die UV-Lichtdesinfektionseinrichtung (5) UV-A-LEDs (12), die UV-A-Strahlung im Wellenlängenbereich 380-315 nm ausstrahlt und UV-C-LEDs (8) die UV-Strahlung im Wellenlängenbereich UV-C 280-200 nm (8) ausstrahlen aufweist und wobei ein Akku (13) zur netzunabhängigen Stromversorgung angeordnet ist.

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• METHODS AND REAGENTS FOR DIAGNOSIS OF SARS-COV-2 INFECTION - The present invention relates to a method for diagnosing a SARS-CoV-2 infection comprising the step of detecting the presence or absence of an antibody to SEQ ID NO: 1, preferably IgA class antibody, in a sample from a subject, a method for the differential diagnosis of a coronavirus infection, a use of an antibody to SEQ ID NO: 1, preferably IgA class antibody for diagnosing a SARS-CoV-2 infection or for the differential diagnosis of a coronavirus infection, preferably for distinguishing between a SARS-CoV-2, MERS and NL63, 229E, OC43 and HKU1 infection, and a kit comprising a polypeptide comprising SEQ ID NO: 1 or a variant thereof, preferably coated to a diagnostically useful carrier and one or more, preferably all reagents from the group comprising an antibody to SEQ ID NO: 1, a washing buffer, a means for detecting the presence of an antibody, preferably IgA class antibody, preferably a secondary antibody binding specifically to IgA class antibodies, preferably comprising a detectable label, and a dilution buffer. - link