Covid-19 Sentry

Contents

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

From Preprints

• Missense variants in human ACE2 modify binding to SARS-CoV-2 Spike -
  SARS-CoV-2 infection begins with the interaction of the SARS-CoV-2 Spike (Spike) and human angiotensin-converting enzyme 2 (ACE2). To explore whether population variants in ACE2 might influence Spike binding and hence infection, we selected 10 ACE2 variants based on affinity predictions and prevalence in gnomAD and measured their affinities for Spike receptor binding domain through surface plasmon resonance (SPR). We discovered variants that enhance and reduce binding, including two variants with distinct population distributions that enhanced affinity for Spike. ACE2 p.Ser19Pro ({Delta}{Delta}G = 0.59 {+/-} 0.08 kcal mol-1) is often seen in the gnomAD African cohort (AF = 0.003) whilst p.Lys26Arg ({Delta}{Delta}G = 0.26 {+/-} 0.09 kcal mol-1) is predominant in the Ashkenazi Jewish (AF = 0.01) and European non-Finnish (AF = 0.006) cohorts. Carriers of these alleles may be more susceptible to infection or severe disease and these variants may influence the global epidemiology of Covid-19. We also identified three rare ACE2 variants that strongly inhibited (p.Glu37Lys, {Delta}{Delta}G = -1.33 {+/-} 0.15 kcal mol-1 and p.Gly352Val, predicted {Delta}{Delta}G = -1.17 kcal mol-1) or abolished (p.Asp355Asn) Spike binding. These variants may confer resistance to infection. Finally, we calibrated the mCSM-PPI2 {Delta}{Delta}G prediction algorithm against our SPR data, give new predictions for all possible ACE2 missense variants at the Spike interface and estimate the overall burden of ACE2 variants on Covid-19 phenotypes.
  🖺 Full Text HTML: Missense variants in human ACE2 modify binding to SARS-CoV-2 Spike
• Structure and dynamics of RNA guanine quadruplexes in SARS-CoV-2 genome. Original strategies against emerging viruses -
  Guanine quadruplexes (G4) structures in viral genome have a key role in modulating viruses’ biological activity. While several DNA G4 structures have been experimentally resolved, RNA G4s are definitely less explored. We report the first calculated G4 structure of the RG-1 RNA sequence of SARS-CoV-2 genome, obtained by using a multiscale approach combining quantum and classical molecular modelling and corroborated by the excellent agreement between the corresponding calculated and experimental circular dichroism spectra. We prove the stability of RG-1 G4 arrangement as well as its interaction with G4 ligands potentially inhibiting viral protein translation.
  🖺 Full Text HTML: Structure and dynamics of RNA guanine quadruplexes in SARS-CoV-2 genome. Original strategies against emerging viruses
• Water-triggered, irreversible conformational change of SARS-CoV-2 main protease on passing from the solid state to aqueous solution -
  The main protease from SARS-CoV-2 is a homodimer. Yet, a recent 0.1 ms long molecular dynamics simulation shows that it readily undergoes a symmetry breaking event on passing from the solid state to the aqueous solution. As a result, the subunits present distinct conformations of the binding pocket. By analysing this long time simulation, here we uncover a previously unrecognised role of water molecules in triggering the transition. Interestingly, each subunit presents a different collection of long-lived water molecules. Enhanced sampling methods performed here, along with machine learning approaches, further establish that the transition to the asymmetric state is essentially irreversible.
  🖺 Full Text HTML: Water-triggered, irreversible conformational change of SARS-CoV-2 main protease on passing from the solid state to aqueous solution
• The Role of ATP in the RNA Translocation Mechanism of SARS-CoV-2 NSP13 Helicase -
  The COVID-19 pandemic has demonstrated the need to develop potent and transferable therapeutics to treat coronavirus infections. Numerous antiviral targets are being investigated, but non-structural protein 13 (nsp13) stands out as a highly conserved and yet under studied target. Nsp13 is a superfamily 1 (SF1) helicase that translocates along and unwinds viral RNA in an ATP dependent manner. Currently, there are no available structures of nsp13 from SARS-CoV-1 or SARS-CoV-2 with either ATP or RNA bound presenting a significant hurdle to the rational design of therapeutics. To address this knowledge gap, we have built models of SARS-CoV-2 nsp13 in Apo, ATP, ssRNA and ssRNA+ATP substrate states. Using 30 microseconds of Gaussian accelerated molecular dynamics simulation (at least 6 microseconds per substrate state), these models were confirmed to maintain substrate binding poses that are similar to other SF1 helicases. A gaussian mixture model and linear discriminant analysis structural clustering protocol was used to identify key aspects of the ATP-dependent RNA translocation mechanism. Namely, four RNA-nsp13 structures are identified that exhibit ATP-dependent populations and support the inch-worm mechanism for translocation. These four states are characterized by different RNA-binding poses for motifs Ia, IV, and V and suggest a powerstroke–like motion of domain 2A relative to domain 1A. This structural and mechanistic insight of nsp13 RNA translocation presents novel targets for the further development of antivirals.
  🖺 Full Text HTML: The Role of ATP in the RNA Translocation Mechanism of SARS-CoV-2 NSP13 Helicase
• ESCA pipeline: Easy-to-use SARS-CoV-2 genome Assembler -
  Early sequencing and quick analysis of SARS-CoV-2 genome are contributing to un-derstand the dynamics of COVID19 epidemics and to countermeasures design at global level. Amplicon-based NGS methods are widely used to sequence the SARS-CoV-2 genome and to identify novel variants that are emerging in rapid succession, harboring multiple deletions and amino acid changing mutations. To facilitate the analysis of NGS sequencing data obtained from amplicon-based sequencing methods, here we propose an easy-to-use SARS-CoV-2 genome Assembler: the ESCA pipeline. Results showed that ESCA can perform high quality genome assembly from IonTor-rent and Illumina raw data, and help the user in easily correct low-coverage regions. Moreover, ESCA includes the possibility to compare assembled genomes of multi sample runs through an easy table format.
  🖺 Full Text HTML: ESCA pipeline: Easy-to-use SARS-CoV-2 genome Assembler
• Deamidation drives molecular aging of the SARS-CoV-2 spike receptor-binding motif -
  The spike is the main protein component of the SARS-CoV-2 virion surface. The spike receptor binding motif mediates recognition of the hACE2 receptor, a critical infection step, and is the preferential target for spike-neutralizing antibodies. Post-translational modifications of the spike receptor binding motif can modulate viral infectivity and immune response. We studied the spike protein in search for asparagine deamidation, a spontaneous event that leads to the appearance of aspartic and isoaspartic residues, affecting both the protein backbone and its charge. We used computational prediction and biochemical experiments to identify five deamidation hotspots in the SARS-CoV-2 spike. Similar deamidation hotspots are frequently found at the spike receptor-binding motifs of related sarbecoviruses, at positions that are mutated in emerging variants and in escape mutants from neutralizing antibodies. Asparagine residues 481 and 501 from the receptor-binding motif deamidate with a half-time of 16.5 and 123 days at 37 {degrees}C, respectively. This process is significantly slowed down at 4 {degrees}C, pointing at a strong dependence of spike molecular aging on the environmental conditions. Deamidation of the spike receptor-binding motif decreases the equilibrium constant for binding to the hACE2 receptor more than 3.5-fold. A model for deamidation of the full SARS-CoV-2 virion illustrates that deamidation of the spike receptor-binding motif leads to the accumulation in the virion surface of a chemically diverse spike population in a timescale of days. Our findings provide a mechanism for molecular aging of the spike, with significant consequences for understanding virus infectivity and vaccine development.
  🖺 Full Text HTML: Deamidation drives molecular aging of the SARS-CoV-2 spike receptor-binding motif
• Generation of potent cellular and humoral immunity against SARS-CoV-2 antigens via conjugation to a polymeric glyco-adjuvant -
  The SARS-CoV-2 virus has caused an unprecedented global crisis, and curtailing its spread requires an effective vaccine which elicits a diverse and robust immune response. We have previously shown that vaccines made of a polymeric glyco-adjuvant conjugated to an antigen were effective in triggering such a response in other disease models and hypothesized that the technology could be adapted to create an effective vaccine against SARS-CoV-2. The core of the vaccine platform is the copolymer p(Man-TLR7), composed of monomers with pendant mannose or a toll-like receptor 7 (TLR7) agonist. Thus, p(Man-TLR7) is designed to target relevant antigen-presenting cells (APCs) via mannose-binding receptors and then activate TLR7 upon endocytosis. The p(Man-TLR7) construct is amenable to conjugation to protein antigens such as the Spike protein of SARS-CoV-2, yielding Spike-p(Man-TLR7). Here, we demonstrate Spike-p(Man-TLR7) vaccination elicits robust antigen-specific cellular and humoral responses in mice. In adult and elderly wild-type mice, vaccination with Spike-p(Man-TLR7) generates high and long-lasting titers of anti-Spike IgGs, with neutralizing titers exceeding levels in convalescent human serum. Interestingly, adsorbing Spike-p(Man-TLR7) to the depot-forming adjuvant alum, amplified the broadly neutralizing humoral responses to levels matching those in mice vaccinated with formulations based off of clinically-approved adjuvants. Additionally, we observed an increase in germinal center B cells, antigen-specific antibody secreting cells, activated T follicular helper cells, and polyfunctional Th1-cytokine producing CD4+ and CD8+ T cells. We conclude that Spike-p(Man-TLR7) is an attractive, next-generation subunit vaccine candidate, capable of inducing durable and robust antibody and T cell responses.
  🖺 Full Text HTML: Generation of potent cellular and humoral immunity against SARS-CoV-2 antigens via conjugation to a polymeric glyco-adjuvant
• 6’,6’-Difluoro-aristeromycin is a potent inhibitor of MERS-coronavirus replication -
  The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the lack of treatments to combat infections with human or (potentially) zoonotic CoVs. Thus, it is critical to develop and evaluate antiviral compounds that either directly target CoV functions or modulate host functions involved in viral replication. Here, we demonstrate that low-micromolar concentrations of 6’,6’-difluoro-aristeromycin (DFA), an adenosine nucleoside analogue, strongly inhibit the replication of Middle East respiratory syndrome coronavirus (MERS-CoV) in a cell-based infection assay. DFA was designed to target S-adenosylhomocysteine (SAH) hydrolase and, consequently, may affect intracellular levels of the methyl donor S-adenosylmethionine, which is used by two CoV methyltransferases involved in the capping of the 5 end of the viral mRNAs. Passaging of wild-type MERS-CoV in the presence of DFA selected a mutant with a ~100-fold decreased DFA sensitivity. This drug-resistant population carried various amino acid substitutions in the viral nonstructural proteins (nsp), including mutations in nsp16, which has 2-O-methyltransferase activity, and nsp13, which contains a nucleoside triphosphate hydrolase activity that has also been implicated in CoV capping. Based on our results, we hypothesize that DFA directly or indirectly affects viral cap methylation, either by inhibiting the viral enzymes involved or by binding to SAH hydrolase. We also evaluated the antiviral activity of DFA against other betacoronaviruses, but found it to have limited impact on their replication, while being quite cytotoxic to the Calu-3 cells used for this comparison. Nevertheless, our results justify the further characterization of DFA derivatives as an inhibitor of MERS-CoV replication.
  🖺 Full Text HTML: 6’,6’-Difluoro-aristeromycin is a potent inhibitor of MERS-coronavirus replication
• Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor -
  Severe respiratory disease coronavirus-2 (SARS-CoV-2) causes the most devastating disease, COVID-19, of the recent century. One of the unsolved scientific questions around SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbor the highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). Here, we report the identification of a novel lineage of SARSr-CoVs, including RaTG15 and seven other viruses, from bats at the same location where we found RaTG13 in 2015. Although RaTG15 and the related viruses share 97.2% amino acid sequence identities to SARS-CoV-2 in the conserved ORF1b region, but only show less than 77.6% to all known SARSr-CoVs in genome level, thus forms a distinct lineage in the Sarbecovirus phylogenetic tree. We then found that RaTG15 receptor binding domain (RBD) can bind to and use Rhinolophus affinis bat ACE2 (RaACE2) but not human ACE2 as entry receptor, although which contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we show that none of the known viruses in bat SARSr-CoV-2 lineage or the novel lineage discovered so far use human ACE2 efficiently compared to SARSr-CoV-2 from pangolin or some of the SARSr-CoV-1 lineage viruses. Collectively, we suggest more systematic and longitudinal work in bats to prevent future spillover events caused by SARSr-CoVs or to better understand the origin of SARS-CoV-2.
  🖺 Full Text HTML: Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor
• Probenecid Inhibits SARS-CoV-2 Replication In Vivo and In Vitro -
  Effective vaccines are slowing the COVID-19 pandemic, but SARS-CoV-2 will likely remain an issue in the future making it important to have therapeutics to treat patients. There are few options for treating patients with COVID-19. We show probenecid potently blocks SARS-CoV-2 replication in mammalian cells and virus replication in a hamster model. Furthermore, we demonstrate that plasma concentrations up to 50-fold higher than the protein binding adjusted IC90 value are achievable for 24h following a single oral dose. These data support the potential clinical utility of probenecid to control SARS-CoV-2 infection in humans.
  🖺 Full Text HTML: Probenecid Inhibits SARS-CoV-2 Replication In Vivo and In Vitro
• A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients by phage display is binding to the ACE2-RBD interface and is tolerant to most known recently emerging RBD mutations -
  The novel betacoranavirus SARS-CoV-2 causes a form of severe pneumonia disease, termed COVID-19 (coronavirus disease 2019). Recombinant human antibodies are proven potent neutralizers of viruses and can block the interaction of viral surface proteins with their host receptors. To develop neutralizing anti-SARS-CoV-2 antibodies, antibody gene libraries from convalescent COVID-19 patients were constructed and recombinant antibody fragments (scFv) against the receptor binding domain (RBD) of the S1 subunit of the viral spike (S) protein were selected by phage display. The selected antibodies were produced in the scFv-Fc format and 30 showed more than 80% inhibition of spike (S1-S2) binding to cells expressing ACE2, assessed by flow cytometry screening assay. The majority of these inhibiting antibodies are derived from the VH3-66 V-gene. The antibody STE90-C11 showed a sub nM IC50 in a plaque-based live SARS-CoV-2 neutralization assay. The in vivo efficacy of the antibody was demonstrated in the Syrian hamster and in the hACE2 mice model using a silenced human IgG1 Fc part. The crystal structure of STE90-C11 Fab in complex with SARS-CoV-2-RBD was solved at 2.0 Angstrom resolution showing that the antibody binds at the same region as ACE2 to RBD. The binding and inhibtion of STE90-C11 is not blocked by many known RBD mutations including N439K, L452R, E484K or L452R+E484Q (emerging B.1.617). STE90-C11 derived human IgG1 with Fc-gamma receptor silenced Fc (COR-101) is currently undergoing Phase Ib/II clinical trials for the treatment of moderate to severe COVID-19.
  🖺 Full Text HTML: A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients by phage display is binding to the ACE2-RBD interface and is tolerant to most known recently emerging RBD mutations
• Porndemic? A longitudinal study of pornography use before and during the COVID-19 pandemic in a nationally representative sample of Americans -
  Of the many changes in daily life brought about by the COVID-19 pandemic, social distancing efforts and governmentally mandated lockdowns were among the most drastic. Coinciding with these changes, popular pornography websites made some previously premium content available for free, spurring dramatic increases in traffic to these websites. This increase in time spent at home and reported increases in traffic to specific pornographic websites led to some speculation that pornography use might generally increase over the course of the pandemic and that problematic use might also increase. To test these speculations and quantify the effects of the pandemic and its associated restrictions on social behaviors on pornography use, we analyzed data from a longitudinal sample of American adults. Baseline, nationally representative data were collected in August, 2019 via YouGov (N=2,518). Subsequent data were collected in February, 2020 (n=1,677), May, 2020 (n=1,533), August, 2020 (n=1,470), and October, 2020 (n=1,269). Results indicated that, in May, 2020, immediately following the height of the first wave of pandemic related lockdowns, more people reported past month pornography use than at any other time point. Among those who reported use in May, 2020, only 14% reported increases in use since the start of the pandemic, and their use returned to levels similar to all other users by August of 2020. In general, pornography use trended downward over the pandemic, for both men and women. Problematic pornography use trended downward for men and remained low and unchanged in women. Collectively, these results suggests that many fears about pornography use during pandemic related lockdowns were largely not supported by available data.
  🖺 Full Text HTML: Porndemic? A longitudinal study of pornography use before and during the COVID-19 pandemic in a nationally representative sample of Americans
• Epidemiological characteristics of three SARS-CoV-2 variants of concern and implications for future COVID-19 pandemic outcomes -

  Three SARS-CoV-2 variants classified as variants of concern - B.1.1.7, B.1.351, and P.1 - have spread globally. To characterize their viral and epidemiological properties in support of public health planning, we develop and apply a model-inference system to estimate the changes in transmissibility and immune escape for each variant, based on case and mortality data from the country where each variant emerged. Accounting for under-detection of infection, disease seasonality, concurrent non-pharmaceutical interventions, and mass-vaccination, we estimate that B.1.1.7 has a 46.6% (95% CI: 32.3 - 54.6%) increase in transmissibility but nominal immune escape from protection induced by prior wild-type infection; B.1.351 has a 32.4% (95% CI: 14.6 - 48.0%) increase in transmissibility and 61.3% (95% CI: 42.6 - 85.8%) immune escape; and P.1 has a 43.3% (95% CI: 30.3 - 65.3%) increase in transmissibility and 52.5% (95% CI: 0 - 75.8%) immune escape. Model simulations indicate that B.1.351 and P.1 could supplant B.1.1.7 dominance and lead to increased infections. Our findings highlight the importance of preventing the spread of B.1.351 and P.1, in addition to B.1.1.7, via continued preventive measures, prompt mass-vaccination of all populations, continued monitoring of vaccine efficacy, and possible updating of vaccine formulations to ensure high efficacy.

  🖺 Full Text HTML: Epidemiological characteristics of three SARS-CoV-2 variants of concern and implications for future COVID-19 pandemic outcomes
• SARS-CoV-2 infection of BNT162b2(mRNA)-vaccinated individuals is not restricted to variants of concern or high-risk exposure environments -

  The emergence of SARS-CoV-2 variants of concern (VOC) has raised questions regarding the extent of protection of currently implemented vaccines. Ten “vaccination breakthrough” infections were identified in Alachua County, Florida, among individuals fully vaccinated with the BNT162b2 mRNA vaccine as a result of social or household transmission. Eight individuals presented mild symptoms in the absence of infection with other common respiratory viruses, confirmed using viral genetic sequencing. SARS-CoV-2 genomes were successfully generated for five of the vaccine breakthroughs and 399 individuals in the surrounding area and were included for reference-based phylogenetic investigation. These five individuals were characterized by infection with both VOCs and low-frequency variants present within the surrounding population. Mutations in the Spike protein were consistent with their respective circulating lineages, with the exception of a viable, low-frequency (approximately 1%) B.1.1.7 mutation, which we describe as a mutation of potential concern. The findings indicate that in cases of limited vaccine protection, infection is not restricted to VOCs or high-risk settings, highlighting the critical need for continued testing and monitoring of infection among individuals regardless of vaccination status.

  🖺 Full Text HTML: SARS-CoV-2 infection of BNT162b2(mRNA)-vaccinated individuals is not restricted to variants of concern or high-risk exposure environments
• Short Telomeres and a T-Cell Shortfall in COVID-19: The Aging Effect -

  Transient lymphopenia is a common feature of acute viral respiratory infections. The drastic and prolonged lymphopenia of COVID-19, however, is distinctive and largely stems from falling counts of T cells. This T-cell lymphopenia may contribute to the inordinate rise in COVID-19 mortality with older age, because naive T-cell clonal expansion is telomere length (TL)-dependent and TL of hematopoietic cells shortens with age. Here we present a biologically plausible model that links naive T-cell clonal expansion capacity and age-dependent hematopoietic cell TL (HCTL) shortening to explain the T- cell shortfall and the high COVID-19 mortality in older adults. The model shows that an individual with average HCTL at age twenty years maintains maximal T-cell clonal expansion capacity until the 6th decade of life when this capacity plummets by more than 90% over the next eight years. The collapse coincides with the steep increase in COVID-19 mortality with age. As young adults tend to maintain their relative HCTL over their life course, individuals with above and below average HCTL respectively experience the drop in maximal T-cell clonal expansion capacity at older and younger ages. HCTL metrics may thus explain the vulnerability of older adults to COVID-19 and predict the capacity for T-cell clonal expansion following vaccination against the virus.

  🖺 Full Text HTML: Short Telomeres and a T-Cell Shortfall in COVID-19: The Aging Effect

From Clinical Trials

• Recombinant Hyperimmune Polyclonal Antibody (GIGA-2050) in COVID-19 Patients - Condition:   COVID-19
  Intervention:   Drug: GIGA-2050
  Sponsor:   GigaGen, Inc.
  Not yet recruiting

• Using Text Messages to Improve COVID-19 Vaccination Uptake, an RCT. - Condition:   Covid19
  Intervention:   Behavioral: Text message content
  Sponsors:   Imperial College Healthcare NHS Trust;   Central London CCG;   Imperial College Health Partners;   Institute for Global Health Innovations;   The Behavioural Insights Team
  Not yet recruiting

• Study to Evaluate the Effects of RO7496998 (AT-527) in Non-Hospitalized Adult and Adolescent Participants With Mild or Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: RO7496998;   Drug: Placebo
  Sponsors:   Atea Pharmaceuticals, Inc.;   Hoffmann-La Roche
  Recruiting

• The Role of High Dose Co-trimoxazole in Severe Covid-19 Patients - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: Co-trimoxazole;   Drug: Placebo
  Sponsor:   Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
  Not yet recruiting

• A Study to Evaluate the Safety and Effect of STC3141 Continuous Infusion in Subjects With Severe Corona Virus Disease 2019（COVID-19）Pneumonia - Condition:   Severe COVID-19 Pneumonia
  Intervention:   Drug: STC3141
  Sponsors:   Grand Medical Pty Ltd.;   Trium Clinical Consulting
  Not yet recruiting

• The Effect of Vitamin D Supplementation on COVID-19 Recovery - Condition:   Covid19
  Interventions:   Drug: Vit-D 0.2 MG/ML Oral Solution [Calcidol];   Drug: Physiological Irrigating Solution
  Sponsors:   University of Monastir;   Loussaief Chawki;   Nissaf Ben Alaya;   Cyrine Ben Nasrallah;   Manel Ben Belgacem;   Hela Abroug;   Imen Zemni;   Manel Ben fredj;   Wafa Dhouib
  Completed

• A Phase 2 Study of APX-115 in Hospitalized Patients With Confirmed Mild to Moderate COVID-19. - Condition:   COVID-19
  Interventions:   Drug: APX-115;   Drug: Placebo
  Sponsors:   Aptabio Therapeutics, Inc.;   Covance
  Not yet recruiting

• Prophylaxis for COVID-19: Ivermectin in Close Contacts of COVID-19 Cases (IVERNEX-TUC) - Condition:   Covid19
  Interventions:   Drug: Ivermectin;   Other: Placebo
  Sponsor:   Ministry of Public Health, Argentina
  Recruiting

• Breathing Effort in Covid-19 Pneumonia: Effects of Positive Pressure, Inspired Oxygen Fraction and Decubitus - Condition:   COVID-19 Pneumonia
  Intervention:   Device: Esophageal catheter
  Sponsor:   San Luigi Gonzaga Hospital
  Recruiting

• Mix and Match of the Second COVID-19 Vaccine Dose for Safety and Immunogenicity - Condition:   COVID-19
  Interventions:   Biological: mRNA-1273 SARS-CoV-2 vaccine;   Biological: BNT162b2;   Biological: ChAdOx1-S [recombinant];   Other: 0, 28 day schedule;   Other: 0, 112 day schedule
  Sponsors:   Canadian Immunization Research Network;   Canadian Center for Vaccinology;   BC Children’s Hospital Research Institute;   Children’s Hospital Research Institute of Manitoba;   CHU de Quebec-Universite Laval;   Ottawa Hospital Research Institute;   Northern Alberta Clinical Trials + Research Centre;   Ontario Agency for Health Protection and Promotion;   University of Toronto;   Massachusetts General Hospital
  Not yet recruiting

• Anti COVID 19 Intravenous Immunoglobulin (C-IVIG) Therapy for Severe COVID-19 Patients - Condition:   Covid19
  Intervention:   Biological: Anti COVID 19 Intravenous Immunoglobulin (C-IVIG)
  Sponsors:   Dow University of Health Sciences;   Higher Education Commission (Pakistan)
  Recruiting

• ACTIV-6: COVID-19 Study of Repurposed Medications - Condition:   Covid19
  Intervention:   Drug: Ivermectin Tablets
  Sponsors:   Susanna Naggie, MD;   National Center for Advancing Translational Science (NCATS);   Vanderbilt University Medical Center
  Not yet recruiting

• A Global Phase III Clinical Trial of Recombinant COVID-19 Vaccine (Sf9 Cells) - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 vaccine (Sf9 cells);   Other: Placebo control
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   WestVac Biopharma Co., Ltd.;   West China Hospital
  Not yet recruiting

• Amantadine for COVID-19: A Randomized, Placebo Controlled, Double-blinded, Clinical Trial - Condition:   Covid19
  Interventions:   Drug: Amantadine;   Drug: Lactose monohydrate
  Sponsors:   Copenhagen University Hospital, Hvidovre;   University of Copenhagen
  Not yet recruiting

• 3R Rehabilitation Management of COVID-19 Survivors - Condition:   Covid19
  Interventions:   Other: Cardiopulmonary exercise (centre-based);   Other: Cardiopulmonary exercise (online-based)
  Sponsors:   The Hong Kong Polytechnic University;   Pamela Youde Nethersole Eastern Hospital, Hong Kong;   Queen Elizabeth Hospital, Hong Kong;   Princess Margaret Hospital, Hong Kong;   Tuen Mun Hospital Hong Kong
  Recruiting

From PubMed

• Intragastric and atomized administration of canagliflozin inhibit inflammatory cytokine storm in lipopolysaccharide-treated sepsis in mice: A potential COVID-19 treatment - To date, drugs to attenuate cytokine storm in severe cases of Corona Virus Disease 2019 (COVID-19) are not available. In this study, we investigated the effects of intragastric and atomized administration of canagliflozin (CAN) on cytokine storm in lung tissues of lipopolysaccharides (LPS)-induced mice. Results showed that intragastric administration of CAN significantly and widely inhibited the production of inflammatory cytokines in lung tissues of LPS-induced sepsis mice. Simultaneously,…

• The interaction of the bioflavonoids with five SARS-CoV-2 proteins targets: An in silico study - Flavonoids have been shown to have antioxidant, anti-inflammatory, anti-proliferative, antibacterial and antiviral efficacy. Therefore, in this study, we choose 85 flavonoid compounds and screened them to determine their in-silico interaction with protein targets crucial for SARS-CoV-2 infection. The five important targets chosen were the main protease (Mpro), Spike receptor binding domain (Spike-RBD), RNA - dependent RNA polymerase (RdRp or Nsp12), non-structural protein 15 (Nsp15) of…

• The SARS-CoV-2 SSHHPS Recognized by the Papain-like Protease - Viral proteases are highly specific and recognize conserved cleavage site sequences of ∼6-8 amino acids. Short stretches of homologous host-pathogen sequences (SSHHPS) can be found spanning the viral protease cleavage sites. We hypothesized that these sequences corresponded to specific host protein targets since >40 host proteins have been shown to be cleaved by Group IV viral proteases and one Group VI viral protease. Using PHI-BLAST and the viral protease cleavage site sequences, we searched…

• Tocilizumab in COVID-19: a meta-analysis, trial sequential analysis, and meta-regression of randomized-controlled trials - CONCLUSIONS: For hospitalized COVID-19 patients, there is some evidence that tocilizumab use may be associated with a short-term mortality benefit, but further high-quality data are required. Its benefits may also lie in reducing the need for mechanical ventilation.

• In silico Studies on the Interaction Between Mpro and PLpro From SARS-CoV-2 and Ebselen, its Metabolites and Derivatives - The COVID-19 pandemic caused by the SARS-CoV-2 has mobilized scientific attention in search of a treatment. The cysteine-proteases, main protease (Mpro) and papain-like protease (PLpro) are important targets for antiviral drugs. In this work, we simulate the interactions between the Mpro and PLpro with Ebselen, its metabolites and derivatives with the aim of finding molecules that can potentially inhibit these enzymes. The docking data demonstrate that there are two main interactions between the…

• Anti-IgE monoclonal antibodies as potential treatment in COVID-19 - Coronavirus disease 2019 (COVID-19) is associated with irreversible effects on vital organs, especially the respiratory and cardiac systems. While the immune system plays a key role in the survival of patients to viral infections, in COVID-19, there is a hyperinflammatory immune response evoked by all the immune cells, such as neutrophils, monocytes, and includes release of various cytokines, resulting in an exaggerated immune response, named cytokine storm. This severe, dysregulated immune…

• In silico Exploration of Interactions Between Potential COVID-19 Antiviral Treatments and the Pore of the hERG Potassium Channel-A Drug Antitarget - Background: In the absence of SARS-CoV-2 specific antiviral treatments, various repurposed pharmaceutical approaches are under investigation for the treatment of COVID-19. Antiviral drugs considered for this condition include atazanavir, remdesivir, lopinavir-ritonavir, and favipiravir. Whilst the combination of lopinavir and ritonavir has been previously linked to prolongation of the QT(c) interval on the ECG and risk of torsades de pointes arrhythmia, less is known in this regard about…

• ACE2 and SARS-CoV-2 Infection Risk: Insights From Patients With Two Rare Genetic Tubulopathies, Gitelman’s and Bartter’s Syndromes - COVID-19 is spreading globally with the angiotensin converting enzyme (ACE)-2 serving as the entry point of SARS-CoV-2 virus. This raised concerns how ACE2 and the Renin-Angiotensin (Ang)-System (RAS) are to be dealt with given their roles in hypertension and their involvement in COVID-19’s morbidity and mortality. Specifically, increased ACE2 expression in response to treatment with ACE inhibitors (ACEi) and Ang II receptor blockers (ARBs) might theoretically increase COVID-19 risk by…

• Tranilast: a potential anti-Inflammatory and NLRP3 inflammasome inhibitor drug for COVID-19 - SARS-CoV-2 is a type of beta-CoV that develops acute pneumonia, which is an inflammatory condition. A cytokine storm has been recognized as one of the leading causes of death in patients with COVID-19. ALI and ARDS along with multiple organ failure have also been presented as the consequences of acute inflammation and cytokine storm. It has been previously confirmed that SARS-CoV, as another member of the beta-CoV family, activates NLRP3 inflammasome and consequently develops acute inflammation…

• Epigallocatechin Gallate Inhibits the Uridylate-Specific Endoribonuclease Nsp15 and Efficiently Neutralizes the SARS-CoV-2 Strain - SARS-CoV-2, the coronavirus strain that initiated the COVID-19 pandemic, and its subsequent variants present challenges to vaccine development and treatment. As the coronavirus evades the host innate immune response at the initial stage of infection, the disease can have a long nonsymptomatic period. The uridylate-specific endoribonuclease Nsp15 processes the viral genome for replication and cleaves the polyU sequence in the viral RNA to interfere with the host immune system. This study screened…

• Marine sulfated polysaccharides as potential antiviral drug candidates to treat Corona Virus disease (COVID-19) - The viral infection caused by SARS-CoV-2 has increased the mortality rate and engaged several adverse effects on the affected individuals. Currently available antiviral drugs have found to be unsuccessful in the treatment of COVID-19 patients. The demand for efficient antiviral drugs has created a huge burden on physicians and health workers. Plasma therapy seems to be less accomplishable due to insufficient donors to donate plasma and low recovery rate from viral infection. Repurposing of…

• Azithromycin: Immunomodulatory and Antiviral Properties for SARS-CoV-2 Infection - Azithromycin, a member of the macrolide family of antibiotics, is commonly used to treat respiratory bacterial infections. Nevertheless, multiple pharmacological effects of the drug have been revealed in several investigations. Conceivably, the immunomodulatory properties of azithromycin are among its critical features, leading to its application in treating inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Additionally, azithromycin may directly inhibit…

• DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist - The efficient spread of SARS-CoV-2 resulted in a unique pandemic in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in respiratory mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas….

• Interleukin-6 Inhibition Reduces Neuronal Injury In A Murine Model of Ventilator-Induced Lung Injury - Mechanical ventilation is a known risk factor for delirium, a cognitive impairment characterized by frontal cortex and hippocampal dysfunction. Although interleukin-6 (IL-6) is upregulated in mechanical ventilation-induced lung injury (VILI) and may contribute to delirium, it is not known whether inhibition of systemic IL-6 mitigates delirium-relevant neuropathology. To histologically define neuropathological effects of IL-6 inhibition in an experimental VILI model. VILI was simulated in…

• Marine algal antagonists targeting 3CL protease and spike glycoprotein of SARS-CoV-2: a computational approach for anti-COVID-19 drug discovery - The COVID-19 pandemic has severely destructed human life worldwide, with no suitable treatment until now. SARS-CoV-2 virus is unprecedented, resistance against number of therapeutics and spreading rapidly with high mortality, which warrants the need to discover new effective drugs to combat this situation. This current study is undertaken to explore the antiviral potential of marine algal compounds to inhibit the viral entry and its multiplication using computational analysis. Among the proven…

From Patent Search

• IMPROVEMENTS RELATED TO PARTICLE, INCLUDING SARS-CoV-2, DETECTION AND METHODS THEREFOR - - link

• A COMPREHENSIVE DISINFECTION SYSTEM DURING PANDEMIC FOR PERSONAL ITEMS AND PROTECTIVE EQUIPMENT (PPE) TO SAFEGUARD PEOPLE - The current Covid-19 pandemic has led to an enormous demand for gadgets / objects for personal protection. To prevent the spread of virus, it is important to disinfect commonly touched objects. One of the ways suggested is to use a personal UV-C disinfecting box that is “efficient and effective in deactivating the COVID-19 virus. The present model has implemented the use of a UV transparent material (fused silica quartz glass tubes) as the medium of support for the objects to be disinfected to increase the effectiveness of disinfection without compromising the load bearing capacity. Aluminum foil, a UV reflecting material, was used as the inner lining of the box for effective utilization of the UVC light emitted by the UVC lamps. Care has been taken to prevent leakage of UVC radiation out of the system. COVID-19 virus can be inactivated in 5 minutes by UVC irradiation in this disinfection box - link

• UBIQUITOUS COMPUTING SYSTEM FOR MENTAL HEALTH MONITORING OF PERSON DURING THE PANDEMIC OF COVID-19 - - link

• USE OF IMINOSUGAR COMPOUND IN PREPARATION OF ANTI-SARS-COV-2 VIRUS DRUG - - link

• 一种高灵敏SARS-CoV-2中和抗体的检测方法、检测试剂盒 - 本发明公开了一种高灵敏SARS‑CoV‑2中和抗体的检测方法、检测试剂盒，属于生物医学检测技术领域，本发明试剂盒包括层析试纸、卡壳和样本稀释液，所述层析试纸包括底板、样品垫、结合垫、NC膜和吸水垫，所述NC膜上依次设置有捕获线、检测线和质控线，所述捕获线包被有ACE2蛋白，所述检测线包被有RBD蛋白，所述结合垫设置有RBD蛋白标记物；本发明采用阻断法加夹心法原理提高检测中和抗体的灵敏度，通过添加捕获线的方式，将靶向RBD的非中和抗体提前捕获，保证后续通过夹心法检测中和抗体的特异性。 - link

• 逆转录酶突变体及其应用 - 本发明提供一种MMLV逆转录酶突变体，在野生型MMLV逆转录酶氨基酸序列（如SEQ ID No.1序列所示）中进行七个氨基酸位点的突变，氨基酸突变位点为：R205H；V288T；L304K；G525D；S526D；E531G；E574G。该突变体可以降低MMLV逆转录酶对Taq DNA聚合酶的抑制作用，大大提高了一步法RT‑qPCR的灵敏度。 - link

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

• 用于检测新型冠状病毒的试纸和试剂盒 - 本发明涉及生物技术和免疫检测技术领域，具体涉及一种用于检测新型冠状病毒的试纸和试剂盒。所述试纸或试剂盒含有抗体1和/或抗体2，所述抗体1的重、轻链可变区的氨基酸序列分别如SEQ ID NO:1‑2所示，所述抗体2的重、轻链可变区的氨基酸序列分别如SEQ ID NO:3‑4所示。本发明对于大批量的新型冠状病毒样本，包括新型冠状病毒突变（英国、南非）与非突变株的人血清、鼻咽拭子等样本的检测有普遍检测意义，避免突变株的漏检。 - link

• Fahrgastleitsystem und Verfahren zum Leiten von Fahrgästen -

  Die Erfindung betrifft ein Fahrgastleitsystem zum Leiten von mit einem Fahrzeug (1) mit wenigstens zwei Türen (2.L, 2.R) transportieren Fahrgästen (3), mit wenigstens einem Sensor (4) zur Überwachung der Fahrgäste (3), wenigstens einem Anzeigemittel (5) zur Ausgabe von Leitinformationen, wenigstens einem Aktor zum Öffnen oder Verriegeln einer Tür (2.L, 2.R) und wenigstens einer Recheneinheit (7). Das erfindungsgemäße Fahrgastleitsystem ist dadurch gekennzeichnet, dass die Recheneinheit (7) dazu eingerichtet ist durch Auswertung vom wenigstens einen Sensor (4) erzeugter Sensordaten zu erkennen an welcher Tür (2.L, 2.R) des Fahrzeugs (1) Fahrgäste (3) ein- und/oder aussteigen möchten und wenigstens eine Tür (2.L, 2.R) für einen Ausstieg festzulegen und/oder wenigstens eine Tür (2.L, 2.R) für einen Einstieg festzulegen, sodass eine Anzahl an Begegnungen von sich durch das Fahrzeug (1) bewegender Fahrgäste (3) und/oder aus dem Fahrzeug (1) aussteigenden und/oder in das Fahrzeug (1) einsteigenden Fahrgästen (3) minimiert wird.

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• Vorrichtung zum Desinfizieren, der Körperpflege oder dergleichen -

  Vorrichtung zum Desinfizieren, der Körperpflege oder dergleichen mittels einer flüssigen oder cremigen Substanz (20), dadurch gekennzeichnet, dass die Vorrichtung mit einem elektrisch betriebenen Erinnerungs-Modul und einem Vorratsbehälter (10) für die Substanz (20) versehen ist, die Substanz (20) in dosierter Menge zur Ausgabeöffnung (9) gefördert wird und die Vorrichtung dazu geeignet ist, am Körper oder der Kleidung einer Person getragen zu werden.

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