Covid-19 Sentry

Contents

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

From Preprints

• Genome sequencing and analysis of an emergent SARS-CoV-2 variant characterized by multiple spike protein mutations detected from the Central Visayas Region of the Philippines -

  The emergence of SARS-CoV-2 variants of concern such as the B.1.1.7, B.1.351 and the P.1 have prompted calls for governments worldwide to increase their genomic biosurveillance efforts. Globally, quarantine and outbreak management measures have been implemented to stem the introduction of these variants and to monitor any emerging variants of potential clinical significance domestically. Here, we describe the emergence of a new SARS-CoV-2 lineage, mainly from the Central Visayas region of the Philippines. This emergent variant is characterized by 13 lineage-defining mutations, including the co-occurrence of the E484K, N501Y, and P681H mutations at the spike protein region, as well as three additional radical amino acid replacements towards the C-terminal end of the said protein. A three-amino acid deletion at positions 141 to 143 (LGV141_143del) in the spike protein was likewise seen in a region preceding the 144Y deletion found in the B.1.1.7 variant. A single amino acid replacement, K2Q, at the N-terminus of ORF8 was also shared by all 33 samples sequenced. The mutation profile of this new virus variant warrants closer investigation due to its potential public health implications. The current distribution of this emergent variant in the Philippines and its transmission are being monitored and addressed by relevant public health agencies to stem its spread in nearby islands and regions in the country.

  🖺 Full Text HTML: Genome sequencing and analysis of an emergent SARS-CoV-2 variant characterized by multiple spike protein mutations detected from the Central Visayas Region of the Philippines
• SARS-CoV-2-host chimeric RNA-sequencing reads do not necessarily signify virus integration into the host DNA -
  The human genome bears evidence of extensive invasion by retroviruses and other retroelements, as well as by diverse RNA and DNA viruses. High frequency of somatic integration of the RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the DNA of infected cells was recently suggested, partly based on the detection of chimeric RNA-sequencing (RNA-seq) reads between SARS-CoV-2 RNA and RNA transcribed from human host DNA. Here, we examined the possible origin of human-SARS-CoV-2 chimeric reads in RNA-seq libraries and provide alternative explanations for their origin. Chimeric reads were frequently detected also between SARS-CoV-2 RNA and RNA transcribed from mitochondrial DNA or episomal adenoviral DNA present in transfected cell lines, which was unlikely the result of SARS-CoV-2 integration. Furthermore, chimeric reads between SARS-CoV-2 RNA and RNA transcribed from nuclear DNA was highly enriched for host exonic, than intronic or intergenic sequences and often involved the same, highly expressed host genes. These findings suggest that human-SARS-CoV-2 chimeric reads found in RNA-seq data may arise during library preparation and do not necessarily signify SARS-CoV-2 reverse transcription, integration in to host DNA and further transcription.
  🖺 Full Text HTML: SARS-CoV-2-host chimeric RNA-sequencing reads do not necessarily signify virus integration into the host DNA
• Scalable, Micro-Neutralization Assay for Qualitative Assessment of SARS-CoV-2 (COVID 19) Virus-Neutralizing Antibodies in Human Clinical Samples -
  As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic was expanding, it was clear that effective testing for the presence of neutralizing antibodies in the blood of convalescent patients would be critical for development of plasma-based therapeutic approaches. To address the need for a high-quality neutralization assay against SARS CoV 2, a previously established fluorescence reduction neutralization assay (FRNA) against Middle East respiratory syndrome coronavirus (MERS-CoV) was modified and optimized. The SARS-CoV-2 FRNA provides a quantitative assessment of a large number of infected cells through use of a high content imaging system. Because of this approach, and the fact that it does not involve subjective interpretation, this assay is more efficient and more accurate than other neutralization assays. In addition, the ability to set robust acceptance criteria for individual plates and specific test wells provided further rigor to this assay. Such agile adaptability avails use with multiple virus variants. By February 2021, the SARS-CoV-2 FRNA had been used to screen over 5,000 samples, including acute and convalescent plasma or serum samples and therapeutic antibody treatments, for SARS-CoV-2 neutralizing titers.
  🖺 Full Text HTML: Scalable, Micro-Neutralization Assay for Qualitative Assessment of SARS-CoV-2 (COVID 19) Virus-Neutralizing Antibodies in Human Clinical Samples
• Analysis of SARS-CoV-2 Mutations Over Time Reveals Increasing Prevalence of Variants in the Spike Protein and RNA-Dependent RNA Polymerase -
  Amid the ongoing COVID-19 pandemic, it has become increasingly important to monitor the mutations that arise in the SARS-CoV-2 virus, to prepare public health strategies and guide the further development of vaccines and therapeutics. The spike (S) protein and the proteins comprising the RNA-Dependent RNA Polymerase (RdRP) are key vaccine and drug targets, respectively, making mutation surveillance of these proteins of great importance. Full protein sequences for the spike proteins and RNA-dependent RNA polymerase proteins were downloaded from the GISAID database, aligned, and the variants identified. Polymorphisms in the protein sequence were investigated at the protein structural level and examined longitudinally in order to identify sequence and strain variants that are emerging over time. Our analysis revealed a group of variants in the spike protein and the polymerase complex that appeared in August, and account for around five percent of the genomes analyzed up to the last week of October. A structural analysis also facilitated investigation of several unique variants in the receptor binding domain and the N-terminal domain of the spike protein, with high-frequency mutations occurring more commonly in these regions. The identification of new variants emphasizes the need for further study on the effects of these mutations and the implications of their increased prevalence, particularly as these mutations may impact vaccine or therapeutic efficacy.
  🖺 Full Text HTML: Analysis of SARS-CoV-2 Mutations Over Time Reveals Increasing Prevalence of Variants in the Spike Protein and RNA-Dependent RNA Polymerase
• Scent dog identification of SARS-CoV-2 infections, similar across different body fluids -
  Background: The main strategy to contain the current SARS-CoV-2 pandemic remains to implement a comprehensive testing, tracing and quarantining strategy until vaccination of the population is adequate. Methods: Ten dogs were trained to detect SARS-CoV-2 infections in beta-propiolactone inactivated saliva samples. The subsequent cognitive transfer performance for the recognition of non-inactivated samples were tested on saliva, urine, and sweat in a randomised, double-blind controlled study. Results: Dogs were tested on a total of 5242 randomised sample presentations. Dogs detected non-inactivated saliva samples with a diagnostic sensitivity of 84% and specificity of 95%. In a subsequent experiment to compare the scent recognition between the three non-inactivated body fluids, diagnostic sensitivity and specificity were 95% and 98% for urine, 91% and 94% for sweat, 82%, and 96% for saliva respectively. Conclusions: The scent cognitive transfer performance between inactivated and non-inactivated samples as well as between different sample materials indicates that global, specific SARS-CoV-2-associated volatile compounds are released across different body secretions, independently from the patient’s symptoms. Funding: The project was funded as a special research project of the German Armed Forces. The funding source DZIF- Fasttrack 1.921 provided us with means for biosampling.
  🖺 Full Text HTML: Scent dog identification of SARS-CoV-2 infections, similar across different body fluids
• Neutralization heterogeneity of United Kingdom and South-African SARS CoV-2 variants in BNT162b2-vaccinated or convalescent COVID-19 healthcare workers -
  There are concerns about neutralizing antibodies (NAb) potency against the newly emerged VOC202012/01 (UK) and 501Y.V2 (SA) SARS-CoV-2 variants in mRNA-vaccinated subjects and in recovered COVID-19 patients. We used a viral neutralization test with a strict 100% neutralizing criterion on UK and SA clinical isolates in comparison with a globally distributed D614G SARS-CoV-2 strain. In two doses BNT162b2-vaccinated healthcare workers (HCW), despite heterogeneity in neutralizing capacity against the three SARS-CoV-2 strains, all sera harbored at least a NAb titer [≥] 1:10 suggesting a certain humoral protection activity either on UK or SA variants. However, six months after mild forms of COVID-19, an important proportion of HCW displayed no neutralizing activity against SA strain. This result supports strong recommendations for vaccination of previously infected subjects.
  🖺 Full Text HTML: Neutralization heterogeneity of United Kingdom and South-African SARS CoV-2 variants in BNT162b2-vaccinated or convalescent COVID-19 healthcare workers
• Previous SARS-CoV-2 infection increases B.1.1.7 cross-neutralization by vaccinated individuals. -
  To assess the potential impact of predominant circulating SARS-CoV-2 variants on neutralizing activity of infected and/or vaccinated individuals, we analyzed neutralization of pseudoviruses expressing the spike of the original Wuhan strain, the D614G and B.1.1.7 variants. Our data show that parameters of natural infection (time from infection and infecting variant) determined cross-neutralization. Importantly, upon vaccination, previously infected individuals developed equivalent B.1.1.7 and Wuhan neutralizing responses. In contrast, uninfected vaccinees showed reduced neutralization against B.1.1.7.
  🖺 Full Text HTML: Previous SARS-CoV-2 infection increases B.1.1.7 cross-neutralization by vaccinated individuals.
• Profiling transcription factor sub-networks in type I interferon signaling and in response to SARS-CoV-2 infection -
  Type I interferons (IFN /{beta}) play a central role in innate immunity to respiratory viruses, including coronaviruses. Genetic defects in type I interferon signaling were reported in a significant proportion of critically ill COVID-19 patients. Extensive studies on interferon-induced intracellular signal transduction pathways led to the elucidation of the Jak-Stat pathway. Furthermore, advances in gene expression profiling by microarrays have revealed that type I interferon rapidly induced multiple transcription factor mRNA levels. In this study, transcription factor profiling in the transcriptome was used to gain novel insights into the role of inducible transcription factors in response to type I interferon signaling in immune cells and in lung epithelial cells after SARS-CoV-2 infection. Modeling the interferon-inducible transcription factor mRNA data in terms of distinct sub-networks based on biological functions such as antiviral response, immune modulation, and cell growth revealed enrichment of specific transcription factors in mouse and human immune cells. The evolutionarily conserved core type I interferon gene expression consists of the inducible transcriptional factor mRNA of the antiviral response sub-network and enriched in granulocytes. Analysis of the type I interferon-inducible transcription factor sub-networks as distinct protein-protein interaction pathways revealed insights into the role of critical hubs in signaling. Interrogation of multiple microarray datasets revealed that SARS-CoV-2 induced high levels of IFN-beta and interferon-inducible transcription factor mRNA in human lung epithelial cells. Transcription factor mRNA of the three major sub-networks regulating antiviral, immune modulation, and cell growth were differentially regulated in human lung epithelial cell lines after SARS-CoV-2 infection and in the tissue samples of COVID-19 patients. A subset of type I interferon-inducible transcription factors and inflammatory mediators were specifically enriched in the lungs and neutrophils of COVID-19 patients. The emerging complex picture of type I IFN transcriptional regulation consists of a rapid transcriptional switch mediated by the Jak-Stat cascade and a graded output of the inducible transcription factor activation that enables temporal regulation of gene expression.
  🖺 Full Text HTML: Profiling transcription factor sub-networks in type I interferon signaling and in response to SARS-CoV-2 infection
• Host-directed FDA-approved drugs with antiviral activity against SARS-CoV-2 identified by hierarchical in silico/in vitro screening methods -
  The unprecedent situation generated by the COVID-19 global emergency prompted us to actively work to fight against this pandemic by searching for repurposable agents among FDA approved drugs to shed light into immediate opportunities for the treatment of COVID-19 patients. In the attempt to proceed toward a proper rationalization of the search for new antivirals among approved drugs, we carried out a hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening to speed up the identification of host-directed therapies against COVID-19 in an effective way. To this end a multi-target virtual screening approach focused on host-based targets related to viral entry followed by the experimental evaluation of the antiviral activity of selected compounds has been carried out. As a result, five different potentially repurposable drugs interfering with viral entry, cepharantine, clofazimine, metergoline, imatinib and efloxate, have been identified.
  🖺 Full Text HTML: Host-directed FDA-approved drugs with antiviral activity against SARS-CoV-2 identified by hierarchical in silico/in vitro screening methods
• Saliva testing is accurate for early-stage and presymptomatic COVID-19 -

  Although nasopharyngeal (NP) samples have been considered the gold standard for COVID-19 testing, variability in viral load across different anatomical sites could theoretically cause NP samples to be less sensitive than saliva or nasal samples in certain cases. Self-collected samples also have logistical advantages over NP samples, making them amenable to population-scale screening. To evaluate sampling alternatives for population screening, we collected NP, saliva, and nasal samples from two cohorts with varied levels and types of symptoms. In a mixed cohort of 60 symptomatic and asymptomatic participants, we found that saliva had 88% concordance with NP when tested in the same testing lab (n = 41), and 68% concordance when tested in different testing labs (n = 19). In a second cohort of 20 participants hospitalized for COVID-19, saliva had 74% concordance with NP tested in the same testing lab, but detected virus in two participants that tested negative with NP on the same day. Medical record review showed that the saliva-based testing sensitivity was related to the timing of symptom onset and disease stage. We find that no sample site will be perfectly sensitive for COVID-19 testing in all situations, and the significance of negative results will always need to be determined in the context of clinical signs and symptoms. Saliva retained high clinical sensitivity while allowing easier collection, minimizing the exposure of healthcare workers and need for personal protective equipment, and making it a viable option for population-scale testing.

  🖺 Full Text HTML: Saliva testing is accurate for early-stage and presymptomatic COVID-19
• Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2 -
  The SARS-CoV-2 Nucleoprotein (NCAP) functions in RNA packaging during viral replication and assembly. Computational analysis of its amino acid sequence reveals a central low-complexity domain (LCD) having sequence features akin to LCDs in other proteins known to function in liquid-liquid phase separation. Here we show that in the presence of viral RNA, NCAP, and also its LCD segment alone, form amyloid-like fibrils when undergoing liquid-liquid phase separation. Within the LCD we identified three 6-residue segments that drive amyloid fibril formation. We determined atomic structures for fibrils formed by each of the three identified segments. These structures informed our design of peptide inhibitors of NCAP fibril formation and liquid-liquid phase separation, suggesting a therapeutic route for Covid-19.
  🖺 Full Text HTML: Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2
• Development of a Rapid Point-Of-Care Test that Measures Neutralizing Antibodies to SARS-CoV-2 -

  As increasing numbers of people recover from and are vaccinated against COVID-19, tests are needed to measure levels of protective, neutralizing antibodies longitudinally to help determine duration of immunity. We developed a lateral flow assay (LFA) that measures levels of neutralizing antibodies in plasma, serum or whole blood. The LFA is based on the principle that neutralizing antibodies inhibit binding of the spike protein receptor-binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2). The LFA compares favorably with authentic SARS-CoV-2 and pseudotype neutralization assays with an accuracy of 98%. Sera obtained from patients with seasonal coronaviruses did not prevent RBD from binding to ACE2. To demonstrate the usefulness of the LFA for measuring antibodies in convalescent plasma used for therapy, we measured conversion of non-immune plasma into strongly neutralizing plasma. This is the first report of a neutralizing antibody test that is rapid, highly portable and relatively inexpensive that might be useful in assessing COVID-19 vaccine-induced immunity.

  🖺 Full Text HTML: Development of a Rapid Point-Of-Care Test that Measures Neutralizing Antibodies to SARS-CoV-2
• Molecular strategies for antibody binding and escape of SARS-CoV-2 and its mutations -
  The COVID19 pandemic, caused by SARS-CoV-2, has infected more than 100 million people worldwide. Due to the rapid spreading of SARS-CoV-2 and its impact, it is paramount to find effective treatments against it. Human neutralizing antibodies are an effective method to fight viral infection. However, the recent discovery of new strains that substantially change the S-protein sequence has raised concern about vaccines and antibodies’ effectiveness. Here, we investigated the binding mechanisms between the S-protein and several antibodies. Multiple mutations were included to understand the strategies for antibody escape in new variants. We found that the combination of mutations K417N and E484K produced higher binding energy to ACE2 than the wild type, suggesting higher efficiency to enter host cells. The mutations’ effect depends on the antibody class. While Class I enhances the binding avidity in the presence of N501Y mutation, class II antibodies showed a sharp decline in the binding affinity. Our simulations suggest that Class I antibodies will remain effective against the new strains. In contrast, Class II antibodies will have less affinity to the S-protein, potentially affecting these antibodies’ efficiency.
  🖺 Full Text HTML: Molecular strategies for antibody binding and escape of SARS-CoV-2 and its mutations
• A Two-Sample Robust Bayesian Mendelian Randomization Method Accounting for Linkage Disequilibrium and Idiosyncratic Pleiotropy With Applications to the COVID-19 Outcome -

  Mendelian randomization (MR) is a statistical method exploiting genetic variants as instrumental variables to estimate the causal effect of modifiable risk factors on an outcome of interest. Despite wide uses of various popular two-sample MR methods based on genome-wide association study summary level data, however, those methods could suffer from potential power loss or/and biased inference when the chosen genetic variants are in linkage disequilibrium (LD), and have relatively large direct effects on the outcome whose distribution might be heavy-tailed which is commonly referred to as the idiosyncratic pleiotropy. To resolve those two issues, we propose a novel Robust Bayesian Mendelian Randomization (RBMR) model that uses the more robust multivariate generalized t-distribution to model such direct effects in a probabilistic model framework which can also incorporate the LD structure explicitly. The generalized t-distribution can be represented as a Gaussian scaled mixture so that our model parameters can be estimated by the EM-type algorithms. We compute the standard errors by calibrating the evidence lower bound (ELBO) using the likelihood ratio test. Through extensive simulation studies, we show that our RBMR has robust performance compared to other competing methods. We also apply our RBMR method to two benchmark data sets and find that RBMR has smaller bias and standard errors. Using our proposed RBMR method, we found that coronary artery disease (CAD) is associated with increased risk of coronavirus disease 2019 (COVID-19). We also develop a user-friendly R package RBMR for public use.

  🖺 Full Text HTML: A Two-Sample Robust Bayesian Mendelian Randomization Method Accounting for Linkage Disequilibrium and Idiosyncratic Pleiotropy With Applications to the COVID-19 Outcome
• Zoonotic spillover of SARS-CoV-2: mink-adapted virus in humans -
  The COVID-19 pandemic caused by SARS-CoV-2 started in fall 2019. A range of different mammalian species, including farmed mink, have been confirmed as susceptible to infection with this virus. We report here the spillover of mink-adapted SARS-CoV-2 from farmed mink to humans after extensive adaptation that lasted at least 3 months. We found the presence of four mutations in the S gene (that gave rise to variant: G75V, M177T, Y453F and C1247F) and others in an isolate obtained from SARS-CoV-2 positive patient.
  🖺 Full Text HTML: Zoonotic spillover of SARS-CoV-2: mink-adapted virus in humans

From Clinical Trials

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

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

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

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

• Dose-Ranging Study to Assess the Safety and Efficacy of Melatonin in Outpatients Infected With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Melatonin;   Drug: Placebo
  Sponsors:   State University of New York at Buffalo;   National Center for Advancing Translational Science (NCATS)
  Not yet recruiting

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

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

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

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

• A Study to Evaluate the Efficacy and Safety of Brilacidin in Hospitalized Participants With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Brilacidin;   Drug: Placebo;   Drug: Standard of Care (SoC)
  Sponsor:   Innovation Pharmaceuticals, Inc.
  Recruiting

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

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

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

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

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

From PubMed

• Expression of SARS-CoV-2 surface glycoprotein fragment 319-640 in E. coli, and its refolding and purification - Sensitive and specific serology tests are essential for epidemiological and public health studies of COVID-19 and for vaccine efficacy testing. The presence of antibodies to SARS-CoV-2 surface glycoprotein (Spike) and, specifically, its receptor-binding domain (RBD) correlates with inhibition of SARS-CoV-2 binding to the cellular receptor and viral entry into the cells. Serology tests that detect antibodies targeting RBD have high potential to predict COVID-19 immunity and to accurately…

• Biomarkers of Cardiac Stress and Cytokine Release Syndrome in COVID-19: A Review - PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the coronavirus 2019 (COVID-19) global pandemic. While primarily a respiratory virus, SARS-CoV-2 can cause myocardial injury. The pattern of injury, referred to as acute COVID-19 cardiovascular syndrome (ACovCS), is defined by cardiac troponin leak in the absence of obstructive coronary artery disease. Although the etiology of the injury is unknown, many speculate that a cytokine release syndrome…

• Therapeutic efficacy of chitosan nanoparticles loaded with BCG-polysaccharide nucleic acid and ovalbumin on airway inflammation in asthmatic mice - In this study, immunoregulation and desensitization therapies were jointly applied in the treatment of asthma, in which chitosan (CS) nanoparticles were used. BALB/c mice were selected and mouse models of asthma were constructed. Mice were divided into 7 groups. A double-chamber plethysmograph, MTT, hematoxylin-eosin staining, and ELISA were used. The expression levels of IL-4 and IL-5 in lung tissue cells were detected. CS-BCG-PSN-OVA sustained-release vaccines significantly alleviated airway…

• Limited specificity of commercially available SARS-CoV-2 IgG ELISAs in serum samples of African origin - CONCLUSIONS: Depending on the chosen antigen and assay protocol, SARS-CoV-2 IgG ELISA specificity may be significantly reduced in certain populations probably due to interference of immune responses to endemic pathogens like other viruses or parasites.

• In vitro activity of itraconazole against SARS-CoV-2 - Although vaccination campaigns are currently being rolled out to prevent coronavirus disease (COVID-19), antivirals will remain an important adjunct to vaccination. Antivirals against coronaviruses do not exist, hence global drug repurposing efforts have been carried out to identify agents that may provide clinical benefit to patients with COVID-19. Itraconazole, an antifungal agent, has been reported to have activity against animal coronaviruses. Using cell-based phenotypic assays, the in vitro…

• Ubiquitin-Modified Proteome of SARS-CoV-2-Infected Host Cells Reveals Insights into Virus-Host Interaction and Pathogenesis - The outbreak of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a serious threat to global public health. The mechanism of pathogenesis and the host immune response to SARS-CoV-2 infection are largely unknown. In the present study, we applied a quantitative proteomic technology to identify and quantify the ubiquitination changes that occur in both the virus and the Vero E6 cells during SARS-CoV-2 infection. By…

• The potential of rapalogs to enhance resilience against SARS-CoV-2 infection and reduce the severity of COVID-19 - COVID-19 disproportionately affects older people, with likelihood of severe complications and death mirroring that of other age-associated diseases. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) has been shown to delay or reverse many age-related phenotypes, including declining immune function. Rapamycin (sirolimus) and rapamycin derivatives are US Food and Drug Administration-approved inhibitors of mTORC1 with broad clinical utility and well established dosing and safety…

• MERS-CoV and SARS-CoV-2 replication can be inhibited by targeting the interaction between the viral spike protein and the nucleocapsid protein - Background: The molecular interactions between viral proteins form the basis of virus production and can be used to develop strategies against virus infection. The interactions of the envelope proteins and the viral RNA-binding nucleocapsid (N) protein are essential for the assembly of coronaviruses including the Middle East respiratory syndrome coronavirus (MERS-CoV). Methods: Using co-immunoprecipitation, immunostaining, and proteomics analysis, we identified a protein interacting with the…

• Polyunsaturated omega-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry - The strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efficacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based…

• Potential neutralizing antibodies discovered for novel corona virus using machine learning - The fast and untraceable virus mutations take lives of thousands of people before the immune system can produce the inhibitory antibody. The recent outbreak of COVID-19 infected and killed thousands of people in the world. Rapid methods in finding peptides or antibody sequences that can inhibit the viral epitopes of SARS-CoV-2 will save the life of thousands. To predict neutralizing antibodies for SARS-CoV-2 in a high-throughput manner, in this paper, we use different machine learning (ML) model…

• Flavonoids against the SARS-CoV-2 induced inflammatory storm - The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of…

• Design, Synthesis and Biological Evaluation of 2-Aminoquinazolin-4(3H)-one Derivatives as Potential SARS-CoV-2 and MERS-CoV Treatments - Despite the rising threat of fatal coronaviruses, there are no general proven effective antivirals to treat them. 2-Aminoquinazolin-4(3H)-one derivatives were newly designed, synthesized, and investigated to show the inhibitory effects on SARS-CoV-2 and MERS-CoV. Among the synthesized derivatives, 7-chloro-2-((3,5-dichlorophenyl)amino)quinazolin-4(3H)-one (9g) and 2-((3,5-dichlorophenyl)amino)-5-hydroxyquinazolin-4 (3H)-one (11e) showed the most potent anti-SARS-CoV-2 activities (IC(50) < 0.25…

• SARS-CoV-2 and other coronaviruses negatively influence mitochondrial quality control: beneficial effects of melatonin - Coronaviruses (CoVs) are a group of single stranded RNA viruses, of which some of them such as SARS-CoV, MERS-CoV, and SARS-CoV-2 are associated with deadly worldwide human diseases. Coronavirus disease-2019 (COVID-19), a condition caused by SARS-CoV-2, results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with high mortality in the elderly and in people with underlying comorbidities. Results from several studies suggest that CoVs localize in mitochondria and…

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

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

From Patent Search

• Sars-CoV-2 vaccine antigens - - link

• SARS-COV-2 BINDING PROTEINS - - link

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

• Aronia-Mundspray -

  Anordnung zum Versprühen einer Substanz in die menschliche Mundhöhle und/oder in den Rachen, dadurch gekennzeichnet, dass die Anordnung eine Sprühflasche mit einer Substanz aufweist, die wenigstens Aroniasaft und eine Alkoholkomponente aufweist.

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

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

• Atemluft-Desinfektionsvorrichtung und Atemschutzmaske -

  Atemluft-Desinfektionsvorrichtung mit einem am Körper eines Lebewesens (2) tragbaren Gehäuse (32), aufweisend:

• eine im Gehäuse (32) ausgebildete frei durchströmbare Atemluft-Bestrahlungskammer (33), die frei von den Strömungswiderstand erhöhenden Einbauten oder Umlenkabschnitten ist, und die an einem Ende (34.1) der Atemluft-Bestrahlungskammer (33) eine im Strömungsweg der Nase und/oder dem Mund des Lebewesens (2) zugewandte erste Durchtrittsöffnung (35.1) aufweist und an einem anderen Ende (34.2) der Atemluft-Bestrahlungskammer (33) eine im Strömungsweg von der Nase und/oder von dem Mund des Lebewesens (2) abgewandte zweite Durchtrittsöffnung (35.2) aufweist, wobei die Atemluft-Bestrahlungskammer (33) von wenigstens einer UV-reflektierenden Kammer-Innenwand (36) begrenzt ist, die aus einem wärmeleitenden Material besteht,
• wenigstens eine im Gehäuse (32) angeordnete, in die Atemluft-Bestrahlungskammer (33) einstrahlende UV-LED-Einheit (31, 31.1, 31.2), die ausgebildet und eingerichtet ist, den Innenraum der Atemluft-Bestrahlungskammer (33) mit UV-Strahlen vollständig zu beaufschlagen, und

• wenigstens einen sich außerhalb der Atemluft-Bestrahlungskammer (33) erstreckenden Kühlkörper (37), der thermisch sowohl an die wenigstens eine UV-LED-Einheit (31, 31.1, 31.2), als auch an die aus dem wärmeleitenden Material bestehende Kammer-Innenwand (36, 39, 40) angekoppelt ist.

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

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

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