Covid-19 Sentry

Contents

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

From Preprints

• Disease, perceived infectibility and threat reactivity: a COVID-19 study -
  We investigate whether COVID-19 exposure changes participants’ threat-detection threshold. Sensitivity to threat was measured in a signal detection task among 397 British adults who also reported how much vulnerable they felt to infectious disease. Participants’ data were then matched to the number of confirmed COVID-19 collected from the NHS database. We found that participants who perceive themselves as more likely to catch infectious diseases displayed a higher negativity bias in response to increased COVID-19 cases. In addition, we found a significant effect of education on participants’ punishment responsiveness in response to COVID-19 exposure. A second wave of data collection is planned exactly two weeks after the first one. The goal of this second wave is to replicate the findings and document the impact of increasing COVID-19 cases and deaths on people’s psychology.
  🖺 Full Text HTML: Disease, perceived infectibility and threat reactivity: a COVID-19 study
• CD47 as a potential biomarker for the early diagnosis of severe COVID-19 -
  The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. Antiviral interventions are only effective prior to the onset of hyperinflammation. Hence, biomarkers are needed for the early identification and treatment of high-risk patients. Here, we show in a range of model systems and data from post mortem samples that SARS-CoV-2 infection results in increased levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells. Systematic literature searches also indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions which may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, CD47 is a candidate biomarker for severe COVID-19. Further research will have to show whether CD47 is a reliable diagnostic marker for the early identification of COVID-19 patients requiring antiviral therapy.
  🖺 Full Text HTML: CD47 as a potential biomarker for the early diagnosis of severe COVID-19
• A Comparison of Performance for Different SARS-Cov-2 Sequencing Protocols -
  SARS-Cov-2 genome sequencing has been identified as a fundamental tool for fighting the COVID-19 pandemic. It is used, for example, for identifying new variants of the virus and for elaborating phylogenetic trees that help to trace the spread of the virus. In the present study we provide a comprehensive comparison between the quality of the assemblies obtained from different sequencing protocols. We demonstrate how some protocols actively promoted by different high-level administrations are inefficient and how less-used alternative protocols show a significant increased performance. This increase of performance could lead to cheaper sequencing protocols and therefore to a more convenient escalation of the sequencing efforts around the world.
  🖺 Full Text HTML: A Comparison of Performance for Different SARS-Cov-2 Sequencing Protocols
• Meta-Research: Citation needed? Wikipedia and the COVID-19 pandemic -
  With the COVID-19 pandemic’s outbreak at the beginning of 2020, millions across the world flocked to Wikipedia to read about the virus. Our study offers an in-depth analysis of the scientific backbone supporting Wikipedia’s COVID-19 articles. Using references as a readout, we asked which sources informed Wikipedia’s growing pool of COVID-19-related articles during the pandemic’s first wave (January-May 2020). We found that coronavirus-related articles referenced trusted media sources and cited high-quality academic research. Moreover, despite a surge in preprints, Wikipedia’s COVID-19 articles had a clear preference for open-access studies published in respected journals and made little use of non-peer-reviewed research uploaded independently to academic servers. Building a timeline of COVID-19 articles on Wikipedia from 2001-2020 revealed a nuanced trade-off between quality and timeliness, with a growth in COVID-19 article creation and citations, from both academic research and popular media. It further revealed how preexisting articles on key topics related to the virus created a framework on Wikipedia for integrating new knowledge. This “scientific infrastructure” helped provide context, and regulated the influx of new information into Wikipedia. Lastly, we constructed a network of DOI-Wikipedia articles, which showed the landscape of pandemic-related knowledge onWikipedia and revealed how citations create a web of scientific knowledge to support coverage of scientific topics like COVID-19 vaccine development. Understanding how scientific research interacts with the digital knowledge-sphere during the pandemic provides insight into how Wikipedia can facilitate access to science. It also sheds light on how Wikipedia successfully fended of disinformation on the COVID-19 and may provide insight into how its unique model may be deployed in other contexts.
  🖺 Full Text HTML: Meta-Research: Citation needed? Wikipedia and the COVID-19 pandemic
• Day-night and seasonal variation of human gene expression across tissues -
  Circadian and circannual cycles trigger physiological changes whose reflection on human transcriptomes remains largely uncharted. We used the time and season of death of 932 individuals from GTEx to jointly investigate transcriptomic changes associated with those cycles across multiple tissues. For most tissues, we found little overlap between genes changing expression during day-night and among seasons. Although all tissues remodeled their transcriptomes, brain and gonadal tissues exhibited the highest seasonality, whereas those in the thoracic cavity showed stronger day-night regulation. Core clock genes displayed marked day-night differences across multiple tissues, which were largely conserved in baboon and mouse, but adapted to their nocturnal or diurnal habits. Seasonal variation of expression affected multiple pathways and were enriched among genes associated with SARS-CoV-2 infection. Furthermore, they unveiled cytoarchitectural changes in brain subregions. Altogether, our results provide the first combined atlas of how transcriptomes from human tissues adapt to major cycling environmental conditions.
  🖺 Full Text HTML: Day-night and seasonal variation of human gene expression across tissues
• Structural O-Glycoform Heterogeneity of the SARS-CoV-2 Spike Protein Receptor-Binding Domain Revealed by Native Top-Down Mass Spectrometry -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes an extensively glycosylated surface spike (S) protein to mediate host cell entry and the S protein glycosylation is strongly implicated in altering viral binding/function and infectivity. However, the structures and relative abundance of the new O-glycans found on the S protein regional-binding domain (S-RBD) remain cryptic because of the challenges in intact glycoform analysis. Here, we report the complete structural characterization of intact O-glycan proteoforms using native top-down mass spectrometry (MS). By combining trapped ion mobility spectrometry (TIMS), which can separate the protein conformers of S-RBD and analyze their gas phase structural variants, with ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS analysis, the O-glycoforms of the S-RBD are comprehensively characterized, so that seven O-glycoforms and their relative molecular abundance are structurally elucidated for the first time. These findings demonstrate that native top-down MS can provide a high-resolution proteoform-resolved mapping of diverse O-glycoforms of the S glycoprotein, which lays a strong molecular foundation to uncover the functional roles of their O-glycans. This proteoform-resolved approach can be applied to reveal the structural O-glycoform heterogeneity of emergent SARS-CoV-2 S-RBD variants, as well as other O-glycoproteins in general.
  🖺 Full Text HTML: Structural O-Glycoform Heterogeneity of the SARS-CoV-2 Spike Protein Receptor-Binding Domain Revealed by Native Top-Down Mass Spectrometry
• In vitro screening of herbal medicinal products for their supportive curing potential in the context of SARS-CoV-2 -
  Background: Herbal medicinal products have a long-standing history of use in the therapy of common respiratory infections. In the COVID-19 pandemic, they may have the potential for symptom relief in non-severe or moderate disease cases. Here we describe the results derived by in vitro screening of five herbal medicinal products with regard to their potential to i) interfere with the binding of the human Angiotensin-converting enzyme 2 (ACE2) receptor with the SARS-CoV-2 Spike S1 protein, ii) modulate the release of the human defensin HBD1 and cathelicidin LL-37 from human A549 lung cells upon Spike S1 protein stimulation and iii) modulate the release of IFN-{gamma} from activated human peripheral blood mononuclear cells (PBMC). The investigated extracts were: Sinupret extract (SINx), Bronchipret thyme-ivy (BRO TE), Bronchipret thyme-primrose (BRO TP), Imupret (IMU), and Tonsipret (TOP). Methods: The inhibitory effect of the herbal medicinal products on the binding interaction of Spike S1 protein and the human ACE2 receptor was measured by ELISA. The effects on intracellular IFN-{gamma} expression in stimulated human PBMCs were measured by flow cytometry. Regulation on HBD1 and LL-37 expression and secretion was assessed in 25d long-term cultured human lung A549 epithelial cells by RT-PCR and ELISA. Results: IMU and BRO TE concentration-dependently inhibited the interaction between spike protein and the ACE2 Receptor. However, this effect was only observed in the cell-free assay at a concentration range which was later on determined as cytotoxic to human PBMC. SINx, TOP and BRO TP significantly upregulated the intracellular expression of antiviral IFN{gamma} from stimulated PBMC. Co-treatment of A549 cells with IMU or BRO TP together with SARS-CoV-2 spike protein significantly upregulated mRNA expression (IMU) and release (IMU and BRO TP) of HBD1 and LL-37 (BRO TP). Conclusions: The in vitro screening results provide first evidence for an immune activating potential of some of the tested herbal medicinal extracts in the context of SARS-CoV-2. Whether these could be helpful in prevention of SARS-CoV-2 invasion or supportive in recovery from SARS-CoV-2 infection needs deeper understanding of the observations.
  🖺 Full Text HTML: In vitro screening of herbal medicinal products for their supportive curing potential in the context of SARS-CoV-2
• Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell -
  Established in vitro models for SARS-CoV-2 infection are limited and include cell lines of non-human origin and those engineered to overexpress ACE2, the cognate host cell receptor. We identified human H522 lung adenocarcinoma cells as naturally permissive to SARS-CoV-2 infection despite complete absence of ACE2. Infection of H522 cells required the SARS-CoV-2 spike protein, though in contrast to ACE2-dependent models, spike alone was not sufficient for H522 infection. Temporally resolved transcriptomic and proteomic profiling revealed alterations in cell cycle and the antiviral host cell response, including MDA5-dependent activation of type-I interferon signaling. Focused chemical screens point to important roles for clathrin-mediated endocytosis and endosomal cathepsins in SARS-CoV-2 infection of H522 cells. These findings imply the utilization of an alternative SARS-CoV-2 host cell receptor which may impact tropism of SARS-CoV-2 and consequently human disease pathogenesis.
  🖺 Full Text HTML: Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell
• The E3 Ubiquitin Ligase RNF5 Facilitates SARS-CoV-2 Membrane Protein-Mediated Virion Release -
  As enveloped virus, SARS-CoV-2 membrane protein (M) mediates viral release from cellular membranes, but the molecular mechanisms of SARS-CoV-2 virions release remain poorly understood. Here, we performed RNAi screening and identified the E3 ligase RNF5 which mediates ubiquitination of SARS-CoV-2 M at residue K15 to enhance the interaction of viral envelope (E) with M. M-E complex ensures the uniform size of viral particles for viral maturation and mediates viral release. Moreover, overexpression of M induces complete autophagy which is dependent on RNF5-mediated ubiquitin modification. M inhibits the activity of lysosome protease, and uses autolysosomes for virion release. Consequently, all these results demonstrate that RNF5 mediates ubiquitin modification of SARS-CoV-2 M to stabilize the M-E complex and induce autophagy for virion release.
  🖺 Full Text HTML: The E3 Ubiquitin Ligase RNF5 Facilitates SARS-CoV-2 Membrane Protein-Mediated Virion Release
• Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees. -
  The emergence of SARS-CoV-2 variants highlighted the need to better understand adaptive immune responses to this virus. It is important to address whether also CD4+ and CD8+ T cell responses are affected, because of the role they play in disease resolution and modulation of COVID-19 disease severity. Here we performed a comprehensive analysis of SARS-CoV-2-specific CD4+ and CD8+ T cell responses from COVID-19 convalescent subjects recognizing the ancestral strain, compared to variant lineages B.1.1.7, B.1.351, P.1, and CAL.20C as well as recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. Similarly, we demonstrate that the sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the variants analyzed. Overall, the results demonstrate that CD4+ and CD8+ T cell responses in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are not substantially affected by mutations found in the SARS-CoV-2 variants.
  🖺 Full Text HTML: Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees.
• Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains -
  We examined the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.7 that arose in the United Kingdom and spread globally. Antibodies elicited by B.1.1.7 infection exhibited significantly reduced recognition and neutralisation of parental strains or of the South Africa B.1.351 variant, than of the infecting variant. The drop in cross-reactivity was more pronounced following B.1.1.7 than parental strain infection, indicating asymmetric heterotypic immunity induced by SARS-CoV-2 variants.
  🖺 Full Text HTML: Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains
• Differential Dynamic Behavior of Prefusion Spike Proteins of SARS Coronaviruses 1 and 2 -
  The coronavirus spike protein, which binds to the same human receptor in both SARS-CoV-1 and 2, has been implied to be a potential source of their differential transmissibility. However, the mechanistic details of spike protein binding to its human receptor remain elusive at the molecular level. Here, we have used an extensive set of unbiased and biased microsecond-level all-atom molecular dynamics (MD) simulations of SARS-CoV-1 and 2 spike proteins to determine the differential dynamic behavior of prefusion spike protein structure in the two viruses. Our results indicate that the active form of the SARS-CoV-2 spike protein is more stable than that of SARS-CoV-1 and the energy barrier associated with the activation is higher in SARS-CoV-2. Our results also suggest that not only the receptor binding domain (RBD) but also other domains such as the N-terminal domain (NTD) could play a role in the differential binding behavior of SARS-CoV-1 and 2 spike proteins.
  🖺 Full Text HTML: Differential Dynamic Behavior of Prefusion Spike Proteins of SARS Coronaviruses 1 and 2
• Trends in Thoracic Impedance and Arrhythmia Burden Among Patients with Implanted Cardiac Defibrillators During the COVID-19 Pandemic -

  Hospitalizations for acute cardiac conditions have markedly declined during the coronavirus disease 2019 (COVID-19) pandemic, yet the cause of this decline is not clear. Using remote monitoring data of 4,029 patients with implantable cardiac defibrillators (ICDs) living in New York City and Minneapolis/Saint Paul, we assessed changes in markers of cardiac status among these patients and compared thoracic impedance and arrhythmia burden in 2019 and 2020 from January through August. We found no change in several key disease decompensation markers among patients with implanted ICD devices during the first phase of COVID-19 pandemic, suggesting that the decrease in cardiovascular hospitalizations in this period is not reflective of a true population-level improvement in cardiovascular health.

  🖺 Full Text HTML: Trends in Thoracic Impedance and Arrhythmia Burden Among Patients with Implanted Cardiac Defibrillators During the COVID-19 Pandemic
• Physical Activity Patterns Among Patients with Intracardiac Remote Monitoring Devices Before, During, and After COVID-19-related Public Health Restrictions -

  Nationwide public health restrictions due to the coronavirus disease 2019 (COVID-19) pandemic have disrupted people9s routine physical activities, yet little objective information is available on the extent to which physical activity has changed among patients with pre-existing cardiac diseases. Using remote monitoring data of 9,924 patients with pacemakers and implantable cardiac defibrillators (ICDs) living in New York City and Minneapolis/Saint Paul, we assessed physical activity patterns among these patients in 2019 and 2020 from January through October. We found marked declines in physical activity among patients with implantable cardiac devices during COVID-19-related restrictions and the reduction was consistent across age and sex subgroups. Moreover, physical activity among these vulnerable patients did not return to pre-restrictions levels several months after COVID-19 restrictions were eased. Our findings highlight the need to consider the unintended consequences of mitigation strategies and develop approaches to encourage safe physical activity during the pandemic.

  🖺 Full Text HTML: Physical Activity Patterns Among Patients with Intracardiac Remote Monitoring Devices Before, During, and After COVID-19-related Public Health Restrictions
• Risk factors for illness severity among pregnant women with confirmed SARS-CoV-2 infection - Surveillance for Emerging Threats to Mothers and Babies Network, 20 state, local, and territorial health departments, March 29, 2020 -January 8, 2021 -

  Background: Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness compared with nonpregnant women. Data to assess risk factors for illness severity among pregnant women with COVID-19 are limited. This study aimed to determine risk factors associated with COVID-19 illness severity among pregnant women with SARS-CoV-2 infection. Methods: Pregnant women with SARS-CoV-2 infection confirmed by molecular testing were reported during March 29, 2020-January 8, 2021 through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Criteria for illness severity (asymptomatic, mild, moderate-to-severe, or critical) were adapted from National Institutes of Health and World Health Organization criteria. Crude and adjusted risk ratios for moderate-to-severe or critical COVID-19 illness were calculated for selected demographic and clinical characteristics. Results: Among 5,963 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 30-39 years, Black/Non-Hispanic race/ethnicity, healthcare occupation, pre-pregnancy obesity, chronic lung disease, chronic hypertension, cardiovascular disease, pregestational diabetes mellitus or gestational diabetes. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions. Conclusions: Pregnant women with moderate-to-severe or critical COVID-19 illness were more likely to be older and have underlying medical conditions compared to pregnant women with asymptomatic infection or mild COVID-19 illness. This information might help pregnant women understand their risk for moderate-to-severe or critical COVID-19 illness and inform targeted public health messaging.

  🖺 Full Text HTML: Risk factors for illness severity among pregnant women with confirmed SARS-CoV-2 infection - Surveillance for Emerging Threats to Mothers and Babies Network, 20 state, local, and territorial health departments, March 29, 2020 -January 8, 2021

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

• COVID-19 Antithrombotic Rivaroxaban Evaluation - Condition:   COVID-19
  Intervention:   Drug: Rivaroxaban 10 mg
  Sponsors:   Hospital Alemão Oswaldo Cruz;   Bayer;   Hospital Israelita Albert Einstein;   Hospital do Coracao;   Hospital Sirio-Libanes;   Hospital Moinhos de Vento;   Brazilian Research In Intensive Care Network;   Brazilian Clinical Research Institute
  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

• 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

• 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

• 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

• Safety and Immunogenicity Study in Adults of AZD1222 and rAd26-S Administered as Heterologous Prime Boost Regimen for the Prevention of Coronavirus Disease 2019 (COVID-19) - Condition:   Covid19
  Interventions:   Biological: AZD1222;   Biological: rAd26-S
  Sponsors:   R-Pharm;   AstraZeneca
  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

• (CBDRA60) to Prevent or Reduce Symptoms of COVID-19 - Condition:   COVID-19
  Interventions:   Dietary Supplement: CBDRA60 supplement;   Dietary Supplement: Placebo
  Sponsors:   Anewsha Therapeutics Inc.;   University of Michigan;   Biologics Consulting
  Not yet recruiting

• Impact of Colchicine and Low-dose Naltrexone on COVID-19 - Condition:   Covid19
  Interventions:   Drug: Colchicine 0.6 mg;   Drug: Naltrexone
  Sponsors:   HealthPartners Institute;   Park Nicollet Foundation
  Enrolling by invitation

• The RAPID COVID Study - Application of Point-of-Care COVID-19 Testing - Condition:   Covid19
  Intervention:   Diagnostic Test: Spartan COVID-19 Platform
  Sponsor:   Ottawa Heart Institute Research Corporation
  Not yet recruiting

From PubMed

• A comprehensive review of hydroxyurea for beta-haemoglobinopathies: the role revisited during COVID-19 pandemic - CONCLUSION: Hydroxyurea is a well-tolerated oral drug which has been in use for many decades. Through its actions of reversible inhibition of ribonucleoside diphosphate reductase enzyme and fetal haemoglobin induction, it exerts many favourable effects on patients with β-haemoglobinopathies. It is currently approved for the treatment of sickle cell disease and non-transfusion dependent β-thalassaemia. Also, there are various observations to suggest that hydroxyurea is an important adjunct in the…

• Low risk of the TMPRSS2 inhibitor camostat mesylate and its metabolite GBPA to act as perpetrators of drug-drug interactions - Camostat mesylate, a potent inhibitor of the human transmembrane protease, serine 2 (TMPRSS2), is currently under investigation for its effectiveness in COVID-19 patients. For its safe application, the risks of camostat mesylate to induce pharmacokinetic drug-drug interactions with co-administered drugs should be known. We therefore tested in vitro the potential inhibition of important efflux (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP, ABCG2)), and uptake transporters…

• Boceprevir, Calpain Inhibitors II and XII, and GC-376 Have Broad-Spectrum Antiviral Activity against Coronaviruses - As the COVID-19 pandemic continues to unfold, the morbidity and mortality are increasing daily. Effective treatment for SARS-CoV-2 is urgently needed. We recently discovered four SARS-CoV-2 main protease (M^(pro)) inhibitors including boceprevir, calpain inhibitors II and XII, and GC-376 with potent antiviral activity against infectious SARS-CoV-2 in cell culture. In this study, we further characterized the mechanism of action of these four compounds using the SARS-CoV-2 pseudovirus…

• Virus-associated ribozymes and nano carriers against COVID-19 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoo tonic, highly pathogenic virus. The new type of coronavirus with contagious nature spread from Wuhan (China) to the whole world in a very short time and caused the new coronavirus disease (COVID-19). COVID-19 has turned into a global public health crisis due to spreading by close person-to-person contact with high transmission capacity. Thus, research about the treatment of the damages caused by the virus or prevention from…

• Management protocol for Fournier’s gangrene in sanitary regime caused by SARS-CoV-2 pandemic: A case report - CONCLUSION: Early management prevents the resection of the other organs by inhibiting the contiguous spread of infection.

• Possible Antiviral Activity of 5-Aminolevulinic Acid in Feline Infectious Peritonitis Virus (Feline Coronavirus) Infection - Feline infectious peritonitis (FIP) is a life-threatening infectious disease of cats caused by virulent feline coronavirus (FIP virus: FIPV). For the treatment of FIP, several effective antivirals were recently reported, but many of these are not available for practical use. 5-amino levulinic acid (5-ALA) is a low-molecular-weight amino acid synthesized in plant and animal cells. 5-ALA can be synthesized in a large amount, and it is widely applied in the medical and agricultural fields. We…

• Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19 - The rapid advancement of the COVID-19 pandemic has prompted an accelerated pursuit to identify effective therapeutics. Stages of the disease course have been defined by viral burden, lung pathology, and progression through phases of the immune response. Immunological factors including inflammatory cell infiltration and cytokine storm have been associated with severe disease and death. Many immunomodulatory therapies for COVID-19 are currently being investigated, and preliminary results support…

• Modalities and Mechanisms of Treatment for Coronavirus Disease 2019 - Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly throughout the world. Although COVID-19 has a relatively low case severity rate compared to SARS and Middle East Respiratory syndrome it is a major public concern because of its rapid spread and devastating impact on the global economy. Scientists and clinicians are urgently trying to identify drugs to combat the virus with hundreds of clinical trials…

• Inhibition of ACE2 Expression by Ascorbic Acid Alone and its Combinations with Other Natural Compounds - CONCLUSION: Our study provides valuable experimental confirmation of the efficacy of micronutrients in controlling ACE2 expression-the coronavirus cellular “entry” point. It further validates the importance of nutrient interactions in various aspects of cellular metabolism and in considering potential therapeutic applications of nutrient-based approaches. The study shows that ascorbic acid and its combination with some natural compounds could be included in developing preventive and therapeutic…

• Exposure of human intestinal epithelial cells and primary human hepatocytes to trypsin-like serine protease inhibitors with potential antiviral effect - Human intestinal epithelial cell line-6 (HIEC-6) cells and primary human hepatocytes (PHHs) were treated with 3-amidinophenylalanine-derived inhibitors of trypsin-like serine proteases for 24 hours. It was proven that treatment with MI-1900 and MI-1907 was tolerated up to 50 μM in HIEC-6. These inhibitors did not cause elevations in extracellular H(2)O(2) levels and in the concentrations of interleukin (IL)-6 and IL-8 and did not alter occludin distribution in HIEC-6. It was also found that…

• Ginkgolic acid and anacardic acid are specific covalent inhibitors of SARS-CoV-2 cysteine proteases - CONCLUSIONS: Our finding provides two novel natural products as promising SARS-CoV-2 antivirals.

• Mechanisms of COVID-19 Entry into the Cell: Potential Therapeutic Approaches Based on Virus Entry Inhibition in COVID-19 Patients with Underlying Diseases - The Coronavirus disease 2019 (COVID-19) virus spread from Wuhan, China, in 2019 and is spreading rapidly around the world. COVID-19 victims are almost associated with cardiovascular disease, high blood pressure, diabetes, and other underlying diseases. Concerning the high prevalence of these disorders, widespread mortality threatens global society, and its fatality rate may increase with increasing COVID-19 prevalence in countries with older populations. Therefore, evaluating patients’ clinical…

• A new class of alpha-ketoamide derivatives with potent anticancer and anti-SARS-CoV-2 activities - Inhibitors of the proteasome have been extensively studied for their applications in the treatment of human diseases such as hematologic malignancies, autoimmune disorders, and viral infections. Many of the proteasome inhibitors reported in the literature target the non-primed site of proteasome’s substrate binding pocket. In this study, we designed, synthesized and characterized a series of novel α-keto phenylamide derivatives aimed at both the primed and non-primed sites of the proteasome. In…

• Glucosylceramide synthase inhibitors prevent replication of SARS-CoV-2 and Influenza virus - The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major threat to global health. Vaccines are ideal solutions to prevent infection, but treatments are also needed for those who have contracted the virus to limit negative outcomes, when vaccines are not applicable. Viruses must cross host cell membranes during their lifecycle, creating a dependency on processes involving membrane dynamics. Thus, in this study we examined whether the…

• Platelet-Activating Immune Complexes Identified in Critically Ill COVID-19 Patients Suspected of Heparin-Induced Thrombocytopenia - CONCLUSIONS: Our study identifies platelet-activating ICs as a novel mechanism that contributes to critically ill COVID-19.

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

• 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

• 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

• 检测新冠病毒的方法及试剂盒 - 本发明公开了一种检测新冠病毒的方法及试剂盒。其中，该方法包括以下步骤：1）采集样本；2）采用核酸释放剂提取核酸；3）采用LAMP扩增进行检测，其中，核酸释放剂包括：热敏蛋白酶1000U/L~10000U/L、Tris‑HCl 5~50 mmol/L、曲拉通X‑100体积百分比0.05%_{0.5%和金属离子螯合剂0.1}0.5mmol/L，其余为无菌水，热敏蛋白酶为≥55℃加热5~10分钟会完全失活的蛋白酶。应用本发明的检测新冠病毒的方法及试剂盒，检测新冠病毒，检测周期短，操作简单方便，检测结果通俗易懂，检测特异性高，检测成本低。 - link

• 一种新型冠状病毒拉曼光谱数据中心的构建方法 - 本发明公开了一种新型冠状病毒拉曼光谱数据中心的构建方法，该方法包括以下步骤：S1.构建新冠病毒结构蛋白拉曼光谱数据库；S2.构建新冠病毒核酸拉曼光谱数据库；S3.构建新冠病毒颗粒拉曼光谱数据库；S4.构建新冠病毒临床检测样本拉曼光谱数据库；将各新型冠状病毒拉曼光谱数据库存入新型冠状病毒拉曼光谱检测服务器构成新型冠状病毒拉曼光谱数据中心。本发明有效建立了一套完整的新型冠状病毒拉曼光谱数据库，为新冠病毒拉曼检测技术提供可靠的标准数据支撑，有效提高检测结果的准确性及置信度。 - link