Covid-19 Sentry

Contents

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

From Preprints

• Societal Change and Wisdom: Insights from the World after Covid Project -
  How will the world change as a result of the Covid-19 pandemic? What can people do to best adapt to the societal changes ahead? To answer these questions, over the course of the summer-fall 2020 we launched the World After COVID Project, interviewing more than 50 of the world’s leading scholars in the behavioral and social sciences, including fellows of national academies and presidents of major scientific societies. Experts independently shared their thoughts on what effects the COVID-19 pandemic will have on our societies and provided advice for successful response to new challenges and opportunities. Using mixed-method and natural language processing analyses, we distilled and analyzed these predictions and suggestions, observing a diversity of scenarios. Results also show that half of the experts approach their post-Covid predictions dialectically, highlighting both positive and negative features of the same prediction. Moreover, prosocial goals and meta-cognition—two chief tenants of the Common Wisdom model—were evident in their recommendations for how to cope with possible changes. The project provides a time capsule of experts’ predictions during major societal changes. We discuss implications for strengthening focus on prediction (vs. mere explanation) in psychological science as well as the value of uncertainty and dialecticism in forecasting.
  🖺 Full Text HTML: Societal Change and Wisdom: Insights from the World after Covid Project
• Potential Pfizer-BioNTech SARS CoV-2 mRNA Faulty Vaccine Design: Could it Reason for the Post Vaccination Sudden Death Reports? -
  The public has a moral and legal right to know the potential hazards of COVID-19 newly approved vaccines to freely decide whether to receive any, after an informed personalized risk benefit ratio is provided. Since most of the serious adverse effects and fatalities are reported with the Pfizer-BioNTech SARS CoV-2 mRNA vaccine and a faulty design has been suggested by another researcher, we suggest that there is a high likelihood for a short-term potential hazard that might be a company specific, to be also compared it to its Moderna’s counterpart. We discuss the potential autoimmune risk that is associated with mRNA-based vaccines liking it with some of the newly reported post vaccination reports of serious adverse effects including sudden death. Importantly, we recommend CDC to change its neutral recommendation and to advice against administration of nucleic acid-based vaccines to persons complaining from autoimmune diseases and to suspend the emergency approval granted to Pfizer-BioNTech SARS CoV-2 mRNA vaccine until full investigations are performed and discussed.
  🖺 Full Text HTML: Potential Pfizer-BioNTech SARS CoV-2 mRNA Faulty Vaccine Design: Could it Reason for the Post Vaccination Sudden Death Reports?
• Exploring the natural origins of SARS-CoV-2 -
  The lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2 and the distance (~1500 km) from Wuhan to Yunnan province, where the closest evolutionary related coronaviruses circulating in horseshoe bats have been identified, is fueling speculation on the natural origins of SARS-CoV-2. Here we analyse SARS-CoV-2's related horseshoe bat and pangolin Sarbecoviruses and confirm Rhinolophus affinis continues to be the likely reservoir species as its host range extends across Central and Southern China. This would explain the bat Sarbecovirus recombinants in the West and East China, trafficked pangolin infections and bat Sarbecovirus recombinants linked to Southern China. Recent ecological disturbances as a result of changes in meat consumption could then explain SARS-CoV-2 transmission to humans through direct or indirect contact with the reservoir wildlife, and subsequent emergence towards Hubei in Central China. The only way, however, of finding the animal progenitor of SARS-CoV-2 as well as the whereabouts of its close relatives, very likely capable of posing a similar threat of emergence in the human population and other animals, will be by increasing the intensity of our sampling.
  🖺 Full Text HTML: Exploring the natural origins of SARS-CoV-2
• CCR1 regulatory variants linked to pulmonary macrophage recruitment in severe COVID-19 -
  Genome-wide association studies have identified 3p21.31 as the main risk locus for severe symptoms and hospitalization in COVID-19 patients. To elucidate the mechanistic basis of this genetic association, we performed a comprehensive epigenomic dissection of the 3p21.31 locus. Our analyses pinpoint activating variants in regulatory regions of the chemokine receptor-encoding CCR1 gene as potentially pathogenic by enhancing infiltration of monocytes and macrophages into the lungs of patients with severe COVID-19.
  🖺 Full Text HTML: CCR1 regulatory variants linked to pulmonary macrophage recruitment in severe COVID-19
• Emerging SARS-CoV-2 variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies -
  SARS-CoV-2 Spike-specific antibodies contribute the majority of the neutralizing activity in most convalescent human sera. Two SARS-CoV-2 variants, N501Y.V1 (also known as B.1.1.7 lineage or VOC-202012/01) and N501Y.V2 (B.1.351 lineage), reported from the United Kingdom and South Africa, contain several mutations in the receptor binding domain of Spike and are of particular concern. To address the infectivity and neutralization escape phenotypes potentially caused by these mutations, we used SARS-CoV-2 pseudovirus system to compare the viral infectivity, as well as the neutralization activities of convalescent sera and monoclonal antibodies (mAbs) against SARS-CoV-2 variants. Our results showed that N501Y Variant 1 and Variant 2 increase viral infectivity compared to the reference strain (wild-type, WT) in vitro. At 8 months after symptom onset, 17 serum samples of 20 participants (85%) retaining titers of ID50 >40 against WT pseudovirus, whereas the NAb titers of 8 samples (40%) and 18 samples (90%) decreased below the threshold against N501Y.V1 and N501Y.V2, respectively. In addition, both N501Y Variant 1 and Variant 2 reduced neutralization sensitivity to most (6/8) mAbs tested, while N501Y.V2 even abrogated neutralizing activity of two mAbs. Taken together the results suggest that N501Y.V1 and N501Y.V2 reduce neutralization sensitivity to some convalescent sera and mAbs.
  🖺 Full Text HTML: Emerging SARS-CoV-2 variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies
• Human embryonic stem cell-derived cardiomyocytes express SARS-CoV-2 host entry proteins: screen to identify inhibitors of infection -
  Patients with cardiovascular comorbidities are more susceptible to severe infection with SARS-CoV-2, known to directly cause pathological damage to cardiovascular tissue. We outline a screening platform using human embryonic stem cell-derived cardiomyocytes, confirmed to express the protein machinery critical for SARS-CoV-2 infection, and a pseudotyped virus system. The method has allowed us to identify benztropine and DX600 as novel inhibitors of SARS-CoV-2 infection.
  🖺 Full Text HTML: Human embryonic stem cell-derived cardiomyocytes express SARS-CoV-2 host entry proteins: screen to identify inhibitors of infection
• Human airway cells prevent SARS-CoV-2 multibasic cleavage site cell culture adaptation -
  Virus propagation methods generally use transformed cell lines to grow viruses from clinical specimens, which may force viruses to rapidly adapt to cell culture conditions, a process facilitated by high viral mutation rates. Upon propagation in VeroE6 cells, SARS-CoV-2 may mutate or delete the multibasic cleavage site (MBCS) in the spike protein that facilitates serine protease-mediated entry into human airway cells. We report that propagating SARS-CoV-2 on the human airway cell line Calu-3 - that expresses serine proteases - prevents MBCS mutations. Similar results were obtained using a human airway organoid-based culture system for SARS-CoV-2 propagation. Thus, in-depth knowledge on the biology of a virus can be used to establish methods to prevent cell culture adaptation.
  🖺 Full Text HTML: Human airway cells prevent SARS-CoV-2 multibasic cleavage site cell culture adaptation
• Insights from Genomes and Genetic Epidemiology of SARS-CoV-2 isolates from the state of Andhra Pradesh -
  Coronavirus disease (COVID-19) emerged from a city in China and has now spread as a global pandemic affecting millions of individuals. The causative agent, SARS-CoV-2 is being extensively studied in terms of its genetic epidemiology using genomic approaches. Andhra Pradesh is one of the major states of India with the third-largest number of COVID-19 cases with limited understanding of its genetic epidemiology. In this study, we have sequenced 293 SARS-CoV-2 genome isolates from Andhra Pradesh with a mean coverage of 13,324X. We identified 564 high-quality SARS-CoV-2 variants, out of which 15 are novel. A total of 18 variants mapped to RT-PCR primer/probe sites, and 4 variants are known to be associated with an increase in infectivity. Phylogenetic analysis of the genomes revealed the circulating SARS-CoV-2 in Andhra Pradesh majorly clustered under the clade A2a (94%), while 6% fall under the I/A3i clade, a clade previously defined to be present in large numbers in India. To the best of our knowledge, this is the most comprehensive genetic epidemiological analysis performed for the state of Andhra Pradesh.
  🖺 Full Text HTML: Insights from Genomes and Genetic Epidemiology of SARS-CoV-2 isolates from the state of Andhra Pradesh
• DINC-COVID: A webserver for ensemble docking with flexible SARS-CoV-2 proteins -
  Motivation: Recent efforts to computationally identify inhibitors for SARS-CoV-2 proteins have largely ignored the issue of receptor flexibility. We have implemented a computational tool for ensemble docking with the SARS-CoV-2 proteins, including the main protease (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp). Results: Ensembles of other SARS-CoV-2 proteins are being prepared and made available through a user-friendly docking interface. Plausible binding modes between conformations of a selected ensemble and an uploaded ligand are generated by DINC, our parallelized meta-docking tool. Binding modes are scored with three scoring functions, and account for the flexibility of both the ligand and receptor. Additional details on our methods are provided in the supplementary material. Availability: dinc-covid.kavrakilab.org . Supplementary information: Details on methods for ensemble generation and docking are provided as supplementary data online.
  🖺 Full Text HTML: DINC-COVID: A webserver for ensemble docking with flexible SARS-CoV-2 proteins
• The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus -
  SARS-CoV-1 and SARS-CoV-2 are not phylogenetically closely related; however, both use the ACE2 receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three sequences of a novel sarbecovirus from Rwanda and Uganda which are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario; and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2, and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions such as Africa, where these viruses have only recently been discovered.
  🖺 Full Text HTML: The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus
• A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process -
  SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral main protease is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N and C-terminus. Herein, we used X-ray crystallography to characterize an immature form of the main protease. We propose that this form preludes the cis-cleavage of N-terminal residues within the dimer, leading to the mature active site. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the main protease bound to its endogenous N and C-terminal residues during the formation of the tetramer. This quaternary form is also present in solution, suggesting a transitional state during the C-terminal trans-cleavage.
  🖺 Full Text HTML: A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process
• Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus) -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic virus that has caused the global COVID-19 pandemic. Tracing the evolution and transmission of the virus is crucial to respond to and control the pandemic through appropriate intervention strategies. This paper reports and analyses genomic mutations in the coding regions of SARS-CoV-2 and their probable protein secondary structure and solvent accessibility changes, which are predicted using deep learning models. Prediction results suggest that mutation D614G in the virus spike protein, which has attracted much attention from researchers, is unlikely to make changes in protein secondary structure and relative solvent accessibility. Based on 6,324 viral genome sequences, we create a spreadsheet dataset of point mutations that can facilitate the investigation of SARS-CoV-2 in many perspectives, especially in tracing the evolution and worldwide spread of the virus. Our analysis results also show that coding genes E, M, ORF6, ORF7a, ORF7b and ORF10 are most stable, potentially suitable to be targeted for vaccine and drug development.
  🖺 Full Text HTML: Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus)
• Increased Expression of Chondroitin Sulfotransferases following AngII may Contribute to Pathophysiology Underlying Covid-19 Respiratory Failure: Impact may be Exacerbated by Decline in Arylsulfatase B Activity -
  The precise mechanisms by which Covid-19 infection leads to hypoxia and respiratory failure have not yet been elucidated. Interactions between sulfated glycosaminoglycans (GAGs) and the SARS-CoV-2 spike glycoprotein have been identified as participating in viral adherence and infectivity. The spike glycoprotein binds to respiratory epithelium through the angiotensin converting enzyme 2 (ACE2) receptor, which endogenously interacts with Angiotensin (Ang) II to yield Angiotensin 1-7. In this report, we show that stimulation of human vascular smooth muscle cells by Ang II leads to increased mRNA expression of two chondroitin sulfotransferases (CHST11 and CHST15), which are required for synthesis of chondroitin 4-sulfate (C4S) and chondroitin 4,6-disulfate (CSE), respectively. Also, increased total sulfated GAGs, increased sulfotransferase activity, and increased expression of the proteoglycans biglycan, syndecan, perlecan, and versican followed treatment by Ang II. Candesartan, an Angiotensin II receptor blocker (Arb), largely, but incompletely, inhibited these increases, and the differences from baseline remained significant. These results suggest that another effect of Ang II also contributes to the increased expression of chondroitin sulfotransferases, total sulfated GAGs, and proteoglycans. We hypothesize that activation of ACE2 may contribute to these increases and suggest that the SARS-CoV-2 spike glycoprotein interaction with ACE2 may also increase chondroitin sulfotransferases, sulfated GAGs, and proteoglycans and thereby contribute to viral adherence to bronchioalveolar cells and to respiratory compromise in SARS-CoV-2 infection.
  🖺 Full Text HTML: Increased Expression of Chondroitin Sulfotransferases following AngII may Contribute to Pathophysiology Underlying Covid-19 Respiratory Failure: Impact may be Exacerbated by Decline in Arylsulfatase B Activity
• Temporal evolution and adaptation of SARS-COV 2 codon usage -
  The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has caused an unprecedented pandemic. Since the first sequenced whole-genome of SARS-CoV-2 on January 2020, the identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. In this study, we compared 134,905 SARS-CoV-2 genomes isolated from all affected countries since the outbreak of this novel coronavirus with the first sequenced genome in Wuhan, China to quantify the evolutionary divergence of SARS-CoV-2. Thus, we compared the codon usage patterns of SARS-CoV-2 genes encoding the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), RNA-dependent RNA polymerase (RdRp). The polyproteins ORF1a and ORF1b were examined separately. We found that SARS-CoV-2 tends to diverge over time by accumulating mutations on its genome and, specifically, on the sequences encoding proteins N and S. Interestingly, different patterns of codon usage were observed among these genes. Genes S and N tend to use a narrower set of synonymous codons that are better optimized to the human host. Conversely, genes E and M consistently use the broader set of synonymous codons, which does not vary in respect to the reference genome. CAI and SiD time evolutions show a tendency to decrease that emerge for most genes. Forsdyke plots are used to study the nature of mutations and they show a rapid evolutionary divergence of each gene, due to the low values of x-intercepets.
  🖺 Full Text HTML: Temporal evolution and adaptation of SARS-COV 2 codon usage
• Effects of Diabetes and Blood Glucose on COVID-19 Mortality: A Retrospective Observational Study -

  OBJECTIVE To investigate the association of diabetes and blood glucose on mortality of patients with Coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS This is a retrospective observational study of all patients with COVID-19 admitted to Huo-Shen-Shan Hospital, Wuhan, China. The hospital was built only for treating COVID-19 and opened on February 5, 2020. The primary endpoint is all-cause mortality during hospitalization. RESULTS Among 2877 hospitalized patients, 15.5% (387/2877) had a history of diabetes and 1.9% (56/2877) died in hospital. After adjustment for confounders, patients with diabetes had a 2-fold increase in the hazard of mortality as compared to patients without diabetes (adjusted HR 2.11, 95%CI: 1.16-3.83, P=0.014). The glucose above 4mmol/L was significantly associated with subsequent mortality on COVID-19(adjusted HR 1.17, 95%CI: 1.10-1.24, per 1mmol/L increase, P<0.001). CONCLUSIONS Diabetes and glucose were associated with increased mortality in patients with COVID-19. These data support that blood glucose should be properly controlled for possibly better survival outcomes in patients with COVID-19.

  🖺 Full Text HTML: Effects of Diabetes and Blood Glucose on COVID-19 Mortality: A Retrospective Observational Study

From Clinical Trials

• Dexamethasone for COVID-19 - Condition:   Covid19
  Intervention:   Drug: Dexamethasone
  Sponsor:   University of Oklahoma
  Not yet recruiting

• Fluvoxamine Administration in Moderate SARS-CoV-2 (COVID-19) Infected Patients - Condition:   Covid19
  Interventions:   Drug: Placebo;   Drug: Fluvoxamine
  Sponsor:   SigmaDrugs Research Ltd.
  Recruiting

• The (HD)IVACOV Trial (The High-Dose IVermectin Against COVID-19 Trial) - Condition:   Covid19
  Interventions:   Drug: Ivermectin 0.6mg/kg/day;   Drug: Ivermectin 1.0mg/kg/day;   Drug: Placebo;   Drug: Hydroxychloroquine
  Sponsor:   Corpometria Institute
  Not yet recruiting

• APT™ T3X on the COVID-19 Contamination Rate - Condition:   COVID-19
  Interventions:   Drug: Tetracycline hydrochloride 3%;   Drug: Placebo
  Sponsors:   University of Nove de Julho;   Santa Casa de Misericórdia de Porto Alegre
  Not yet recruiting

• A Study of ORTD-1 in Patients Hospitalized With COVID-19 Related Pneumonia - Condition:   COVID-19
  Interventions:   Drug: ORTD-1 low dose;   Drug: ORTD-1 mid dose;   Drug: ORTD-1 high dose;   Other: Vehicle control
  Sponsor:   Oryn Therapeutics, LLC
  Recruiting

• Rapid Diagnosis of COVID-19 by Chemical Analysis of Exhaled Air - Condition:   Covid19
  Intervention:   Diagnostic Test: Performance evaluation (sensitivity and specificity) for COVID-19 diagnosis of the Vocus PTR-TOF process
  Sponsor:   Hospices Civils de Lyon
  Not yet recruiting

• COVID-19 Immunologic Antiviral Therapy With Omalizumab - Condition:   Covid19
  Interventions:   Biological: Omalizumab;   Other: Placebo
  Sponsor:   McGill University Health Centre/Research Institute of the McGill University Health Centre
  Not yet recruiting

• IMUNOR® Preparation in the Prevention of COVID-19 - Condition:   Covid19
  Intervention:   Drug: IMUNOR
  Sponsor:   University Hospital Ostrava
  Not yet recruiting

• Clinical Experimentation With Tenofovir Disoproxyl Fumarate and Emtricitabine for COVID-19 - Condition:   Covid19
  Interventions:   Drug: Vitamin C 500 MG Oral Tablet;   Drug: Tenofovir disoproxyl fumarate 300 MG Oral Tablet;   Drug: Tenofovir disoproxyl fumarate 300 MG plus emtricitabine 200 MG Oral Tablet
  Sponsors:   Universidade Federal do Ceara;   Conselho Nacional de Desenvolvimento Científico e Tecnológico;   São José Hospital for Infectious Diseases - HSJ;   Central Laboratory of Public Health of Ceará - Lacen-CE
  Recruiting

• Safety and Efficacy of Doxycycline and Rivaroxaban in COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Doxycycline Tablets;   Drug: Rivaroxaban 15Mg Tab;   Combination Product: Hydroxychloroquine and Azithromycin
  Sponsor:   Yaounde Central Hospital
  Recruiting

• A Phase Ⅱb Clinical Trial of Recombinant Corona Virus Disease-19 (COVID-19) Vaccine (Sf9 Cells) - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 vaccine (Sf9 cells);   Biological: Placebo
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   West China Hospital
  Not yet recruiting

• Study to Evaluate the Safety, Tolerability, and Efficacy of BGE-175 in Participants ≥ 60 Years of Age and Hospitalized With Coronavirus Disease 2019 (COVID-19) That Are Not in Respiratory Failure - Condition:   Covid19
  Interventions:   Drug: BGE-175;   Other: Placebo
  Sponsor:   BioAge Labs, Inc.
  Not yet recruiting

• Antiseptic Mouth Rinses to Reduce Salivary Viral Load in COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: Betadine© bucal 100 mg/ml;   Drug: Oximen® 3%;   Drug: Clorhexidine Dental PHB©;   Drug: Vitis Xtra Forte©;   Drug: Distilled Water
  Sponsors:   Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana;   Hospital Universitario Fundación Jiménez Díaz;   Hospital Universitario General de Villalba;   Hospital Universitario Infanta Elena;   Hospital Universitario Virgen de la Arrixaca;   Hospital Clínico Universitario de Valencia;   Dentaid SL
  Completed

• Pilot Study of Cefditoren Pivoxil in COVID-19 Patients With Mild to Moderate Pneumonia - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Cefditoren pivoxil 400mg
  Sponsor:   Meiji Pharma Spain S.A.
  Recruiting

• Early Use of Hyperimmune Plasma in COVID-19 - Condition:   Covid19
  Intervention:   Other: hyperimmune plasma
  Sponsors:   Catherine Klersy;   Policlinico San Matteo Pavia Fondazione IRCCS
  Recruiting

From PubMed

• Antibody persistence in the first six months following SARS-CoV-2 infection among hospital workers: a prospective longitudinal study - CONCLUSION: Neutralizing antibodies persisted at six months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies.

• Interleukin 1α: a comprehensive review on the role of IL-1α in the pathogenesis and targeted treatment of autoimmune and inflammatory diseases - The interleukin (IL)-1 family member IL-1α is a ubiquitous and pivotal pro-inflammatory cytokine. The IL-1α precursor is constitutively present in nearly all cell types in health, but is released upon necrotic cell death as a bioactive mediator. IL-1α is also expressed by infiltrating myeloid cells within injured tissues. The cytokine binds the IL-1 receptor 1 (IL-1R1), as does IL-1β, and induces the same pro-inflammatory effects. Being a bioactive precursor released upon tissue damage and...

• Serum Amyloid P inhibits single stranded RNA-induced lung inflammation, lung damage, and cytokine storm in mice - SARS-CoV-2 is a single stranded RNA (ssRNA) virus and contains GU-rich sequences distributed abundantly in the genome. In COVID-19, the infection and immune hyperactivation causes accumulation of inflammatory immune cells, blood clots, and protein aggregates in lung fluid, increased lung alveolar wall thickness, and upregulation of serum cytokine levels. A serum protein called serum amyloid P (SAP) has a calming effect on the innate immune system and shows efficacy as a therapeutic for fibrosis...

• Host cell glutamine metabolism as a potential antiviral target - A virus minimally contains a nucleic acid genome packaged by a protein coat. The genome and capsid together are known as the nucleocapsid, which has an envelope containing a lipid bilayer (mainly phospholipids) originating from host cell membranes. The viral envelope has transmembrane proteins that are usually glycoproteins. The proteins in the envelope bind to host cell receptors, promoting membrane fusion and viral entry into the cell. Virus-infected host cells exhibit marked increases in...

• Experimental data using candesartan and captopril indicate no double-edged sword effect in COVID-19 - The key link between renin-angiotensin system (RAS) and COVID-19 is ACE2 (angiotensin converting enzyme-2), which acts as a double-edged sword, because ACE2 increases the tissue anti-inflammatory response but it is also the entry receptor for the virus. There is an important controversy on several drugs that regulate RAS activity and possibly ACE2, and are widely used, particularly by patients most vulnerable to severe COVID-19. In the lung of healthy rats, we observed that candesartan (an...

• Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19 - SARS-CoV-2 infection has spread uncontrollably worldwide while it remains unknown how vulnerable populations, such as Down syndrome (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections with respiratory complications and present signs of auto-inflammation. They also present with multiple comorbidities that are associated with poorer COVID-19 prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2...

• The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein - The multifunctional nucleocapsid (N) protein in SARS-CoV-2 binds the ~30 kb viral RNA genome to aid its packaging into the 80-90 nm membrane-enveloped virion. The N protein is composed of N-terminal RNA-binding and C-terminal dimerization domains that are flanked by three intrinsically disordered regions. Here we demonstrate that the N protein's central disordered domain drives phase separation with RNA, and that phosphorylation of an adjacent serine/arginine rich region modulates the physical...

• Dynamic competition between SARS-CoV-2 NSP1 and mRNA on the human ribosome inhibits translation initiation - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta-CoV that recently emerged as a human pathogen and is the causative agent of the COVID-19 pandemic. A molecular framework of how the virus manipulates host cellular machinery to facilitate infection remains unclear. Here, we focus on SARS-CoV-2 NSP1, which is proposed to be a virulence factor that inhibits protein synthesis by directly binding the human ribosome. We demonstrate biochemically that NSP1 inhibits translation of...

• Quinacrine, an Antimalarial Drug with Strong Activity Inhibiting SARS-CoV-2 Viral Replication In Vitro - Quinacrine (Qx), a molecule used as an antimalarial, has shown anticancer, antiprion, and antiviral activity. The most relevant antiviral activities of Qx are related to its ability to raise pH in acidic organelles, diminishing viral enzymatic activity for viral cell entry, and its ability to bind to viral DNA and RNA. Moreover, Qx has been used as an immunomodulator in cutaneous lupus erythematosus and various rheumatological diseases, by inhibiting phospholipase A2 modulating the Th1/Th2...

• Cholesterol 25-hydroxylase suppresses porcine deltacoronavirus infection by inhibiting viral entry - Cholesterol 25-hydroxylase (CH25 H) is a key enzyme regulating cholesterol metabolism and also acts as a broad antiviral host restriction factor. Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus that can cause vomiting, diarrhea, dehydration and even death in newborn piglets. In this study, we found that PDCoV infection significantly upregulated the expression of CH25H in IPI-FX cells, a cell line of porcine ileum epithelium. Overexpression of CH25H inhibited...

• Inhibition of drug-metabolizing enzymes by Qingfei Paidu decoction: implication of herb-drug interactions in COVID-19 pharmacotherapy - Corona Virus Disease 2019 (COVID-19) has spread all over the world and brings significantly negative effects on human health. To fight against COVID-19 in a more efficient way, drug-drug or drug-herb combinations are frequently used in clinical settings. The concomitant use of multiple medications may trigger clinically relevant drug/herb-drug interactions. This study aims to assay the inhibitory potentials of Qingfei Paidu decoction (QPD, a Chinese medicine compound formula recommended for...

• Targeting SARS-CoV-2 Viral Proteases as a Therapeutic Strategy to Treat COVID-19 - The 21^(st) century has witnessed three outbreaks of coronavirus (CoVs) infections caused by severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV and SARS-CoV-2. Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, spreads rapidly and since the discovery of the first COVID-19 infection in December 2019, has caused 1.2 million deaths worldwide and 226,777 deaths in the United States alone. The high amino acid similarity between SARS-CoV-1 and SARS-CoV-2...

• COVID-19, Angiotensin-Converting Enzyme 2 and Renin-Angiotensin System Inhibition: Implications for Practice - CONCLUSIONS: Further randomized trials are needed to answer definitely the question of whether RAS inhibitors are harmful or beneficial to patients with COVID-19.

• In silico study indicates antimalarials as direct inhibitors of SARS-CoV-2-RNA dependent RNA polymerase - Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a global pandemic. RNA-dependent RNA polymerase (RdRp) is the key component of the replication or transcription machinery of coronavirus. Therefore SARS-CoV-2-RdRp has been chosen as an important target for the development of antiviral drug(s). During the early pandemic of the COVID-19, chloroquine and hydroxychloroquine were suggested by the researchers for the prevention or...

• C1 Esterase Inhibition: Targeting Multiple Systems in COVID-19 - No abstract

From Patent Search

• COVID-19 CLASSIFICATION RECOGNITION METHOD BASED ON CT IMAGES OF LUNGS - - link

• A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof - - link

• Covid 19 - Chewing Gum - - link

• STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19 - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - link

• Fahrzeuglüftungssystem und Verfahren zum Betreiben eines solchen Fahrzeuglüftungssystems -

  Die Erfindung betrifft ein Fahrzeuglüftungssystem (1) zum Belüften einer Fahrgastzelle (2) eines Fahrzeugs (3), mit einem Umluftpfad (5). Die Erfindung ist gekennzeichnet durch eine wenigstens abschnittsweise in einen Umluftansaugbereich (4) des Umluftpads (5) hineinreichende Sterilisationseinrichtung (6), wobei die Sterilisationseinrichtung (6) dazu eingerichtet ist von einem aus der Fahrgastzelle (2) entnommenen Luftstrom getragene Schadstoffe zu inaktivieren und/oder abzutöten.

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• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• "AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2." - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex. - link

• Mund-Nasen-Bedeckung -

  Mund-Nasen-Bedeckung (1), wobei die Mund-Nasen-Bedeckung (1) mindestens an einem Ohr eines Trägers magnetisch befestigbar ist.

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• Haptens, hapten conjugates, compositions thereof and method for their preparation and use - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels. - link