Covid-19 Sentry

Contents

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

From Preprints

• Panama in a Pandemic: The Digital Divide Became News -
  This documentary research explores, describes, and analyzes the media coverage of the digital divide in Panama during the first six months of the COVID-19 pandemic. Based on van Dijk’s theoretical postulates, I frame the digital access gap in the context of an unequal society. The review reveals that serious asymmetries, defined by socioeconomic status and territorial division, prevail in Panama. The discontent generated by difficulties in accessing online education triggered wide coverage by the media. In most cases, however, media outlets treated this phenomenon with little explanatory depth. Given the centrality that this problem has acquired and its future implications, the paper provides recommendations in the fields of journalism, research, education, and public policy, which aim to contribute to the understanding of the digital divide and how it could be corrected.
  🖺 Full Text HTML: Panama in a Pandemic: The Digital Divide Became News
• Quality of life and its factors in the COVID19 pandemic situation. Results of Stage 1 studies during the pandemic growth period -
  Objectives. This study aimed to understand the relationship between resource gains and losses, coping, and quality of life during the growth phase of the COVID-19 pandemic. Material and Methods. The Internet-based survey covered 353 individuals who had participated in a psychological support project operated by one of the non-governmental organisations in Lublin, Poland, in the 12 months prior to the outbreak of the pandemic. The questionnaire used in the study contained questions to collect sociodemographic data and psychometric scales to measure resource gains and losses (Conservation of Resources – Evaluation), quality of life (World Health Organization [WHO] Quality of Life-BREF), and strategies of coping with the pandemic situation (modified Brief Cope). Results. Higher global quality of life occurred with higher gains and minor losses, as well as with coping through planning, positive reframing, emotional support seeking, reduced substance use tendency, low self-blame, avoidance, and disengagement. Moreover, helplessness-based coping strategies were found to mediate both the relationship between resource gains and quality of life and between resource loss and quality of life. Conclusions. Factors that may reduce people’s quality of life during the COVID-19 pandemic are an increase in losses and limited gains, experienced over the six months preceding the pandemic, as well as not using active, meaning-oriented, and support-seeking coping strategies, but using avoidance behaviours instead. Coping strategies specific to people experiencing helplessness are a mediating mechanism between losses and limited gains of resources and quality of life. Objectives. This study aimed to understand the relationship between resource gains and losses, coping, and quality of life during the growth phase of the COVID-19 pandemic. Material and Methods. The Internet-based survey covered 353 individuals who had participated in a psychological support project operated by one of the non-governmental organisations in Lublin, Poland, in the 12 months prior to the outbreak of the pandemic. The questionnaire used in the study contained questions to collect sociodemographic data and psychometric scales to measure resource gains and losses (Conservation of Resources – Evaluation), quality of life (World Health Organization [WHO] Quality of Life-BREF), and strategies of coping with the pandemic situation (modified Brief Cope). Results. Higher global quality of life occurred with higher gains and minor losses, as well as with coping through planning, positive reframing, emotional support seeking, reduced substance use tendency, low self-blame, avoidance, and disengagement. Moreover, helplessness-based coping strategies were found to mediate both the relationship between resource gains and quality of life and between resource loss and quality of life. Conclusions. Factors that may reduce people’s quality of life during the COVID-19 pandemic are an increase in losses and limited gains, experienced over the six months preceding the pandemic, as well as not using active, meaning-oriented, and support-seeking coping strategies, but using avoidance behaviours instead. Coping strategies specific to people experiencing helplessness are a mediating mechanism between losses and limited gains of resources and quality of life.
  🖺 Full Text HTML: Quality of life and its factors in the COVID19 pandemic situation. Results of Stage 1 studies during the pandemic growth period
• High Mortality Rate Due to Novel Coronavirus and Deficient Magnesium Intake by Countries -
  The mortality rate due to COVID-19 is much lower in Asia and Africa than in developed countries in Europe and the United States (West), and this has become an issue that is attracting a great deal of attention. On the other hand, it has recently become clear that the mineral Magnesium (Mg) is significantly related to human immune function, and most people in the West have insufficient Mg intake. Furthermore, it has become clear that the conventional standards for Mg intake are inadequate to indicate insufficient Mg intake. This report shows that regional and national differences in Mg intake are largely responsible for the differences in deaths per infected people (D/IP) caused by COVID-19: the West and Indonesia are considered to have low dietary Mg intakes, resulting in high D/IP; and India･Bangladesh and Africa are the opposite.
  🖺 Full Text HTML: High Mortality Rate Due to Novel Coronavirus and Deficient Magnesium Intake by Countries
• Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike -
  Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with an unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded monoclonal antibodies (mAbs) from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found 7 major mAb competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of mAb-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. mAbs that competed for binding the original S isolate bound differentially to S variants, suggesting the protective importance of otherwise-redundant recognition. The results furnish a global atlas of the S-specific memory B cell repertoire and illustrate properties conferring robustness against emerging SARS-CoV-2 variants.
  🖺 Full Text HTML: Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike
• SARS-CoV-2 genomic surveillance identifies naturally occurring truncations of ORF7a that limit immune suppression -

  Over 200,000 whole-genome sequences of SARS-CoV-2 have been determined for viruses isolated from around the world. These sequences have been critical for understanding the spread and evolution of SARS-CoV-2. Using global phylogenomics, we show that mutations frequently occur in the C-terminal end of ORF7a. We have isolated one of these mutant viruses from a patient sample and used viral challenge experiments to demonstrate that Δ115 mutation results in a growth defect. ORF7a has been implicated in immune modulation, and we show that the C-terminal truncation results in distinct changes in interferon-stimulated gene expression. Collectively, this work indicates that ORF7a mutations occur frequently and that these changes affect viral mechanisms responsible for suppressing the immune response.

  🖺 Full Text HTML: SARS-CoV-2 genomic surveillance identifies naturally occurring truncations of ORF7a that limit immune suppression
• Analysis of COVID-19 case numbers: adjustment for diagnostic misclassification on the example of German case reporting data -

  Background: Reported COVID-19 case numbers are key to monitoring pandemic spread and decision-making on policy measures but require careful interpretation as they depend substantially on testing strategy. A high and targeted testing activity is essential for a successful Test-Trace-Isolate strategy. However, it also leads to increased numbers of false-positives and can foster a debate on the actual pandemic state, which can slow down action and acceptance of containment measures. Aim: We evaluate the impact of misclassification in COVID-19 diagnostics on reported case numbers and estimated numbers of disease onsets (epidemic curve). Methods: We developed a statistical adjustment of reported case numbers for erroneous diagnostic results that facilitates a misclassification-adjusted real-time estimation of the epidemic curve based on nowcasting. Under realistic misclassification scenarios, we provide adjusted case numbers for Germany and illustrate misclassification-adjusted nowcasting for Bavarian data. Results: We quantify the impact of diagnostic misclassification on time-series of reported case numbers, highlighting the relevance of a specificity smaller than one when test activity changes over time. Adjusting for misclassification, we find that the increase of cases starting in July might have been smaller than indicated by raw case counts, but cannot be fully explained by increasing numbers of false-positives due to increased testing. The effect of misclassification becomes negligible when true incidence is high. Conclusions: Adjusting case numbers for misclassification can improve this important measure on short-term dynamics of the pandemic and should be considered in data-based surveillance. Further limitations of case reporting data exist and have to be considered.

  🖺 Full Text HTML: Analysis of COVID-19 case numbers: adjustment for diagnostic misclassification on the example of German case reporting data
• Excess Mortality probably due to COVID-19 in Tokyo, Japan between August and October, 2020 -

  Background: As of the mid of December, 2020, the COVID-19 outbreak has been record the highest peak in December, 2020. Nevertheless, no remarkable excess mortality attributable to COVID-19 has been observed. Object: We sought to quantify excess mortality in April using the National Institute of Infectious Diseases (NIID) model. Method: We applied the NIID model to deaths of all causes from 1987 up through December, 2020 for the whole of Japan and up through October for Tokyo. Results: Results in Japan show very few excess mortality in August and October, 2020 It was estimated as 12 and 104. Conversely, in Tokyo, 595 excess mortality was detected between August and October, which was 3.1% and 1.7% of baseline. Discussion and Conclusion: We detected substantial excess mortality in Tokyo but a few in Japan. It might be important to continue to monitor excess mortality of COVID-19 carefully hereafter.

  🖺 Full Text HTML: Excess Mortality probably due to COVID-19 in Tokyo, Japan between August and October, 2020
• Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response -
  The rapid spread of COVID-19 underscores the need for new treatments. Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARS-CoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population. This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection.
  🖺 Full Text HTML: Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response
• Development of Equine Immunoglobulin Fragment F(ab’)2 with High Neutralizing Capability against SARS-CoV-2 -
  The ongoing pandemic, COVID-19, caused by SARS-CoV-2 has taken the world, and especially the scientific community by storm. While vaccines are being introduced into the market, there is also a pressing need to find potential drugs and therapeutic modules. Remdesivir is one of the antivirals currently being used with a limited window of action. As more drugs are being vetted, passive immunotherapy in the form of neutralizing antibodies can provide immediate action to combat the increasing numbers of COVID-positive cases. Herein, we demonstrate that equines hyper-immunized with chemically inactivated SARS-CoV-2 generate high titers of antibody with a strong virus neutralizing potential. ELISA performed with pooled antisera displayed highest immunoglobulin titer on 42 days post-immunization, at 1:51,200 dilutions. F(ab’)2 immunoglobulin fragments generated from the pools also showed very high, antigen-specific affinity at 1:102,400 dilutions. Finally, in vitro virus neutralization assays confirmed that different pools of F(ab’)2 fragments could successfully neutralize SARS-CoV-2 with titers well above 25,000, indicating the potential of this strategy in treating severe COVID-19 cases with high titers. The F(ab’)2 was able to cross neutralize another SARS-CoV-2 strain, demonstrating its efficacy against the emerging viral variants and the importance of this approach in our efforts of eradication of COVID-19. In conclusion, this study demonstrates that virus-neutralizing antibodies raised in equines can potentially be used as a treatment regimen in the form of effective passive immunotherapy to combat COVID-19.
  🖺 Full Text HTML: Development of Equine Immunoglobulin Fragment F(ab’)2 with High Neutralizing Capability against SARS-CoV-2
• The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2 -
  VIR-7831 and VIR-7832 are dual action monoclonal antibodies (mAbs) targeting the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). VIR-7831 and VIR-7832 were derived from a parent antibody (S309) isolated from memory B cells of a 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) survivor. Both mAbs contain an LS mutation in the Fc region to prolong serum half-life and potentially enhance distribution to the respiratory mucosa. In addition, VIR-7832 encodes an Fc GAALIE mutation that has been shown previously to evoke CD8+ T-cells in the context of an in vivo viral respiratory infection. VIR-7831 and VIR-7832 potently neutralize live wild-type SARS-CoV-2 in vitro as well as pseudotyped viruses encoding spike protein from the B.1.1.7, B.1.351 and P.1 variants. In addition, they retain activity against monoclonal antibody resistance mutations that confer reduced susceptibility to currently authorized mAbs. The VIR-7831/VIR-7832 epitope does not overlap with mutational sites in the current variants of concern and continues to be highly conserved among circulating sequences consistent with the high barrier to resistance observed in vitro. Furthermore, both mAbs can recruit effector mechanisms in vitro that may contribute to clinical efficacy via elimination of infected host cells. In vitro studies with these mAbs demonstrated no enhancement of infection. In a Syrian Golden hamster proof-of concept concept wildtype SARS-CoV-2 infection model, animals treated with VIR-7831 had less weight loss, and significantly decreased total viral load and infectious virus levels in the lung compared to a control mAb. Taken together, these data indicate that VIR-7831 and VIR-7832 are promising new agents in the fight against COVID-19.
  🖺 Full Text HTML: The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2
• Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes -
  There is an urgent need to develop effective interventions resistant to the evolving variants of SARS-CoV-2. Nanobodies (Nbs) are stable and cost-effective agents that can be delivered by novel aerosolization route to treat SARS-CoV-2 infections efficiently. However, it remains unknown if they possess broadly neutralizing activities against the prevalent circulating strains. We found that potent neutralizing Nbs are highly resistant to the convergent variants of concern that evade a large panel of neutralizing antibodies (Abs) and significantly reduce the activities of convalescent or vaccine-elicited sera. Subsequent determination of 9 high-resolution structures involving 6 potent neutralizing Nbs by cryoelectron microscopy reveals conserved and novel epitopes on virus spike inaccessible to Abs. Systematic structural comparison of neutralizing Abs and Nbs provides critical insights into how Nbs uniquely target the spike to achieve high-affinity and broadly neutralizing activity against the evolving virus. Our study will inform the rational design of novel pan-coronavirus vaccines and therapeutics.
  🖺 Full Text HTML: Potent neutralizing nanobodies resist convergent circulating variants of SARS-CoV-2 by targeting novel and conserved epitopes
• SARS-CoV-2-specific T Cell Memory is Sustained in COVID-19 Convalescents for 8 Months with Successful Development of Stem Cell-like Memory T Cells -

  Memory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. We conducted direct ex vivo assays to evaluate SARS-CoV-2-specific CD4⁺ and CD8⁺ T cell responses in COVID-19 convalescents up to 254 days post-symptom onset (DPSO). Here, we report that memory T cell responses were maintained during the study period. In particular, we observed sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4⁺ and CD8⁺ T cells detected by activation-induced markers, the proportion of stem cell-like memory T (T_SCM) cells increased, peaking at approximately 120 DPSO. Development of T_SCM cells was confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of T_SCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19. The current study provides insight for establishing an effective vaccination program and epidemiological measurement.

  🖺 Full Text HTML: SARS-CoV-2-specific T Cell Memory is Sustained in COVID-19 Convalescents for 8 Months with Successful Development of Stem Cell-like Memory T Cells
• Naturally-acquired immunity in Syrian Golden Hamsters provides protection from re-exposure to emerging heterosubtypic SARS-CoV-2 variants B.1.1.7 and B.1.351 -
  The ability of acquired immune responses against SARS-CoV-2 to protect after subsequent exposure to emerging variants of concern (VOC) such as B1.1.7 and B1.351 is currently of high significance. Here, we use a hamster model of COVID-19 to show that prior infection with a strain representative of the original circulating lineage B of SARS-CoV-2 induces protection from clinical signs upon subsequent challenge with either B1.1.7 or B1.351 viruses, which recently emerged in the UK and South Africa, respectively. The results indicate that these emergent VOC may be unlikely to cause disease in individuals that are already immune due to prior infection, and this has positive implications for overall levels of infection and COVID-19 disease.
  🖺 Full Text HTML: Naturally-acquired immunity in Syrian Golden Hamsters provides protection from re-exposure to emerging heterosubtypic SARS-CoV-2 variants B.1.1.7 and B.1.351
• Structures and function of locked conformations of SARS-CoV-2 spike -
  The spike protein (S) of SARS-CoV-2 has been observed in three distinct pre-fusion conformations: locked, closed and open. Of these, the locked conformation was not previously observed for SARS-CoV-1 S and its function remains poorly understood. Here we engineered a SARS-CoV-2 S protein construct “S-R/x3” to arrest SARS-CoV-2 spikes in the locked conformation by a disulfide bond. Using this construct we determined high-resolution structures revealing two distinct locked states, with or without the D614G substitution that has become fixed in the globally circulating SARS-CoV-2 strains. The D614G mutation induces a structural change in domain D from locked-1 to locked-2 conformation to alter spike dynamics, promoting transition into the closed conformation from which opening of the receptor binding domain is permitted. The transition from locked to closed conformations is additionally promoted by a change from low to neutral pH. We propose that the locked conformations of S are present in the acidic cellular compartments where virus is assembled and egresses. In this model, release of the virion into the neutral pH extracellular space would favour transition to the closed form which itself can stochastically transition into the open form. The S-R/x3 construct provides a tool for the further structural and functional characterization of the locked conformations of S, as well as how sequence changes might alter S assembly and regulation of receptor binding domain dynamics.
  🖺 Full Text HTML: Structures and function of locked conformations of SARS-CoV-2 spike
• Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19 -
  Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.
  🖺 Full Text HTML: Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19

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

• Diagnostic Performance of the ID Now™ COVID-19 Screening Test Versus Simplexa™ COVID-19 Direct Assay - Condition:   Covid19
  Intervention:   Diagnostic Test: ID Now™ COVID-19 Screening Test
  Sponsor:   Groupe Hospitalier Paris Saint Joseph
  Active, not 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

• 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

• 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

• 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

• Effectiveness of the Adsorbed Vaccine COVID-19 (Coronavac) Among Education and Law Enforcement Professionals With Risk Factors for Severity - Condition:   Covid19
  Intervention:   Biological: Adsorbed SARS-CoV-2 (inactivated) vaccine
  Sponsors:   Fundação de Medicina Tropical Dr. Heitor Vieira Dourado;   Butantan Institute
  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

• COVID-19 Vaccination of Immunodeficient Persons (COVAXID) - Condition:   Covid19
  Intervention:   Biological: Comirnaty (COVID-19, mRNA vaccine)
  Sponsors:   Karolinska University Hospital;   Karolinska Institutet
  Recruiting

• Vitamin D3 Levels in COVID-19 Outpatients From Western Mexico - Condition:   Covid19
  Intervention:   Dietary Supplement: Vitamin D3
  Sponsor:   University of Guadalajara
  Completed

• Dietary Supplements for COVID-19 - Condition:   Covid19
  Interventions:   Drug: Vitamin D3 50,000 IU;   Dietary Supplement: Vitamin C/Zinc;   Dietary Supplement: Vitamin K2/D;   Other: Microcrystalline Cellulose Capsule;   Other: Medium Chain Triglyceride Oil
  Sponsors:   The Canadian College of Naturopathic Medicine;   Ottawa Hospital Research Institute
  Not yet recruiting

From PubMed

• The Preclinical Inhibitor GS441524 in Combination with GC376 Efficaciously Inhibited the Proliferation of SARS-CoV-2 in the Mouse Respiratory Tract - The unprecedented coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious threat to global public health. Development of effective therapies against SARS-CoV-2 is urgently needed. Here, we evaluated the antiviral activity of a remdesivir parent nucleotide analog, GS441524, which targets the coronavirus RNA-dependent RNA polymerase enzyme, and a feline coronavirus prodrug, GC376, which targets its main protease, using a…

• Metabolic programs define dysfunctional immune responses in severe COVID-19 patients - It is unclear why some SARS-CoV-2 patients readily resolve infection while others develop severe disease. By interrogating metabolic programs of immune cells in severe and recovered coronavirus disease 2019 (COVID-19) patients compared with other viral infections, we identify a unique population of T cells. These T cells express increased Voltage-Dependent Anion Channel 1 (VDAC1), accompanied by gene programs and functional characteristics linked to mitochondrial dysfunction and apoptosis. The…

• SARS-CoV-2 Drug Discovery based on Intrinsically Disordered Regions - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a close relative of SARS-CoV-1, causes coronavirus disease 2019 (COVID-19), which, at the time of writing, has spread to over 19.9 million people worldwide. In this work, we aim to discover drugs capable of inhibiting SARS-CoV-2 through interaction modeling and statistical methods. Currently, many drug discovery approaches follow the typical protein structure-function paradigm, designing drugs to bind to fixed three-dimensional…

• Blockade of SARS-CoV-2 infection in vitro by highly potent PI3K-alpha/mTOR/BRD4 inhibitor - Pathogenic viruses like SARS-CoV-2 and HIV hijack the host molecular machinery to establish infection and survival in infected cells. This has led the scientific community to explore the molecular mechanisms by which SARS-CoV-2 infects host cells, establishes productive infection, and causes life-threatening pathophysiology. Very few targeted therapeutics for COVID-19 currently exist, such as remdesivir. Recently, a proteomic approach explored the interactions of 26 of 29 SARS-CoV-2 proteins…

• Molecular mechanisms of Na,K-ATPase dysregulation driving alveolar epithelial barrier failure in severe COVID-19 - A significant number of patients with coronavirus disease 2019 (COVID‑19) develop acute respiratory distress syndrome (ARDS) that is associated with a poor outcome. The molecular mechanisms driving failure of the alveolar barrier upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) infection remain incompletely understood. The Na,K‑ATPase is an adhesion molecule and a plasma membrane transporter that is critically required for proper alveolar epithelial function by both promoting…

• Ribavirin shows antiviral activity against SARS-CoV-2 and downregulates the activity of TMPRSS2 and the expression of ACE2 In Vitro - Ribavirin is a guanosine analog and has a broad-spectrum antiviral activity against RNA viruses. Based on this, we aimed to show the anti-SARS-CoV-2 activity of this drug molecule via in vitro, in silico and molecular techniques. Ribavirin showed antiviral activity in Vero E6 cells following SARS-CoV-2 infection whereas the drug itself did not show any toxic effect over the concentration range tested. In silico analysis suggested that Ribarivin has a broad-spectrum impact on SARS-CoV-2, acting…

• Plant Metabolites as Antiviral Preparations Against Coronaviruses - In 2019-2020, the Coronavirus (CoV) disease 2019 pandemic created a serious challenge for health care systems in several countries worldwide. A cure has not been developed yet and currently used treatment protocols are aimed at relieving clinical symptoms of the disease. This article presents a retrospective review of biologically active compounds of plant origin that can inhibit the reproduction of CoVs, which makes them potential candidates for creating medicinal antiviral preparations against…

• 1’-Ribose cyano substitution allows Remdesivir to effectively inhibit nucleotide addition and proofreading during SARS-CoV-2 viral RNA replication - COVID-19 has recently caused a global health crisis and an effective interventional therapy is urgently needed. Remdesivir is one effective inhibitor for SARS-CoV-2 viral RNA replication. It supersedes other NTP analogues because it not only terminates the polymerization activity of RNA-dependent RNA polymerase (RdRp), but also inhibits the proofreading activity of intrinsic exoribonuclease (ExoN). Even though the static structure of Remdesivir binding to RdRp has been solved and biochemical…

• 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…

• New Acaciin-Loaded Self-Assembled Nanofibers as M(Pro) Inhibitors Against BCV as a Surrogate Model for SARS-CoV-2 - CONCLUSION: The results introduced a new, time/cost-saving strategy for the synthesis of biodegradable NFs without the need for electric current or hazardous cross-linking agents. Moreover, it provided an innovative avenue for the discovery of drugs of herbal origin for the fight against SARS-CoV-2 infection.

• Identification of human immune cell subtypes most responsive to IL-1β-induced inflammatory signaling using mass cytometry - IL-1β is a key mediator of the cytokine storm linked to high morbidity and mortality from COVID-19, and IL-1β blockade with anakinra and canakinumab during COVID-19 infection has entered clinical trials. Using mass cytometry of human peripheral blood mononuclear cells, we identified effector memory CD4^(+) T cells and CD4^(-)CD8(low/-)CD161^(+) T cells, specifically those positive for the chemokine receptor CCR6, as the circulating immune subtypes with the greatest response to IL-1β. This…

• Exploring Spike Protein as Potential Target of Novel Coronavirus and to Inhibit the Viability utilizing Natural Agents - CONCLUSION: With the development of the LY6E gene activator that can inhibit spike protein-ACE2-mediated membrane fusion, new opportunities for SARS-CoV-2 treatment may emerge. Existing antiviral fusion inhibitors and natural compounds targeting spike resistance can serve as a template for further SARS-CoV-2 drug formulation.

• Between two storms, vasoactive peptides or bradykinin underlie severity of COVID-19? - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to be a world-wide pandemic with overwhelming socioeconomic impact. Since inflammation is one of the major causes of COVID-19 complications, the associated molecular mechanisms have been the focus of many studies to better understand this disease and develop improved treatments for patients contracting SARS-CoV-2. Among these, strong emphasis has been placed on pro-inflammatory…

• Calcium sensing receptor hyperactivation through viral envelop protein E of SARS CoV2: A novel target for cardio-renal damage in COVID-19 infection - Over the recent decades, a number of new pathogens have emerged within specific and diverse populations across the globe, namely, the Nipah virus, the Ebola virus, the Zika virus, and coronaviruses (CoVs) to name a few. Recently, a new form of coronavirus was identified in the city of Wuhan, China. Interestingly, the genomic architecture of the virus did not match with any of the existing genomic sequencing data of previously sequenced CoVs. This had led scientists to confirm the emergence of a…

• Association between ABO blood types and coronavirus disease 2019 (COVID-19), genetic associations, and underlying molecular mechanisms: a literature review of 23 studies - An association of various blood types and the 2019 novel coronavirus disease (COVID-19) has been found in a number of publications. The aim of this literature review is to summarize key findings related to ABO blood types and COVID-19 infection rate, symptom presentation, and outcome. Summarized findings include associations between ABO blood type and higher infection susceptibility, intubation duration, and severe outcomes, including death. The literature suggests that blood type O may serve as…

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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• 基于水疱性口炎病毒载体的新型冠状病毒嵌合重组疫苗及其制备方法与应用 - 本发明公开了基于水疱性口炎病毒载体的新型冠状病毒嵌合重组疫苗及其制备方法与应用。该重组疫苗的活性成分为重组病毒rVSV‑SARS‑CoV/2‑RBD，为将水疱性口炎病毒的糖蛋白G替换为嵌合囊膜蛋白S后得到的病毒；所述嵌合囊膜蛋白S为将SARS‑CoV囊膜蛋白S的RBD替换为SARS‑CoV‑2囊膜蛋白S的RBD后得到的蛋白；所述SARS‑CoV囊膜蛋白S的RBD的氨基酸序列为SARS‑CoV囊膜蛋白S氨基酸序列的第315‑536位；所述SARS‑CoV‑2囊膜蛋白S的RBD的氨基酸序列为SARS‑CoV‑2囊膜蛋白S氨基酸序列的第319‑541位。该重组病毒对新冠病毒的疫苗研制具有重要意义。 - 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

• 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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• 制备重组新型冠状病毒Spike蛋白的方法 - 本发明提供了一种制备重组新型冠状病毒Spike蛋白的方法。本发明首先提供以下多肽作为信号肽在制备重组新型冠状病毒Spike蛋白中的应用：SEQ ID No. 10所示氨基酸序列组成的多肽。本发明采用特定信号肽，构建含有编码重组新型冠状病毒Spike蛋白的多核苷酸的表达载体，转染哺乳动物细胞以分泌表达重组新型冠状病毒Spike蛋白，可显著提高Spike蛋白在HEK293细胞中的分泌表达水平。 - link

• 新型冠状病毒抗体检测试剂盒及其制备方法与应用 - 本发明提供一种新型冠状病毒抗体检测试剂盒及其制备方法与应用。所述试剂盒包括：IgG结合分子，抗IgM抗体，荧光标记的新型冠状病毒S1蛋白，荧光标记的新型冠状病毒N蛋白，S1蛋白的hIgG抗体阳性标准品，N蛋白的hIgG抗体阳性标准品，S1蛋白的hIgM抗体阳性标准品，N蛋白的hIgM抗体阳性标准品，阴性对照hIgG抗体样品，阴性对照hIgM抗体样品；其中，所述IgG结合分子与抗IgM抗体负载于不同粒径的纳米颗粒上。本发明的试剂盒用于新型冠状病毒抗体检测，可在1‑2h内快速完成血清中新型冠状病毒中和性抗体的检测，待检样品用量少，特异性强，灵敏度高，重复性好，操作简单，实验室要求低以及安全性高。 - link