Covid-19 Sentry

Contents

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

From Preprints

• Sensitive identification of known and unknown protease activities by unsupervised linear motif deconvolution -
  The cleavage-site specificities for many proteases are not well-understood, restricting the utility of supervised classification methods. We present an algorithm and web interface to overcome this limitation through the unsupervised detection of overrepresented patterns in protein sequence data, providing insight into the mixture of protease activities contributing to a complex system. Here, we apply the RObust LInear Motif Deconvolution (RoLiM) algorithm to confidently detect substrate cleavage patterns for SARS-CoV-2 Mpro protease in N terminome data of an infected human cell line. Using mass spectrometry-based peptide data from a case-control comparison of 341 primary urothelial bladder cancer cases and 110 controls, we identified distinct sequence motifs indicative of increased MMP activity in urine from cancer patients. Evaluation of N terminal peptides from patient plasma post-chemotherapy detected novel Granzyme B/Corin activity. RoLiM will enhance unbiased investigation of peptide sequences to establish the composition of known and uncharacterized protease activities in biological systems.
  🖺 Full Text HTML: Sensitive identification of known and unknown protease activities by unsupervised linear motif deconvolution
• Reduced Incidence of Long-COVID Symptoms Related to Administration of COVID-19 Vaccines Both Before COVID-19 Diagnosis and Up to 12 Weeks After -

  Both clinical trials and studies leveraging real-world data have repeatedly confirmed the three COVID-19 vaccines authorized for use by the Food and Drug Administration are safe and effective at preventing infection, hospitalization, and death due to COVID-19 and a recent observational study of self-reported symptoms provides support that vaccination may also reduce the probability of developing long-COVID. As part of a federated research study with the COVID-19 Patient Recovery Alliance, Arcadia.io performed a retrospective analysis of the medical history of 240,648 COVID-19-infected persons to identity factors influencing the development and progression of long-COVID. This analysis revealed that patients who received at least one dose of any of the three COVID vaccines prior to their diagnosis with COVID-19 were 7-10 times less likely to report two or more long-COVID symptoms compared to unvaccinated patients. Furthermore, unvaccinated patients who received their first COVID-19 vaccination within four weeks of SARS-CoV-2 infection were 4-6 times less likely to report multiple long-COVID symptoms, and those who received their first dose 4-8 weeks after diagnosis were 3 times less likely to report multiple long-COVID symptoms compared to those who remained unvaccinated. This relationship supports the hypothesis that COVID-19 vaccination is protective against long-COVID and that effect persists even if vaccination occurs up to 12 weeks after COVID-19 diagnosis. A critical objective of this study was hypothesis generation, and the authors intend to perform further studies to substantiate the findings and encourage other researchers to as well.

  🖺 Full Text HTML: Reduced Incidence of Long-COVID Symptoms Related to Administration of COVID-19 Vaccines Both Before COVID-19 Diagnosis and Up to 12 Weeks After
• Epoxidized graphene grid for high-throughput high-resolution cryoEM structural analysis -
  Many specimens suffer from low particle density and/or preferred orientation in cryoEM specimen grid preparation, making data collection and structure determination time consuming. We developed an epoxidized graphene grid (EG-grid) that effectively immobilizes protein particles by applying an oxidation reaction using photoactivated ClO2{middle dot} and further chemical modification. The particle density and orientation distribution are both dramatically improved, having enabled us to reconstruct the density map of GroEL and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), at 1.99 and 2.16 [A] resolution from only 504 and 241 micrographs, respectively. A low concentration sample solution of 0.1 mg ml-1 was sufficient to reconstruct a 3.10 [A] resolution density map of SARS-CoV-2 spike protein from 1,163 micrographs. The density maps of V1-ATPase, {beta}-galactosidase, and apoferritin were also reconstructed at 3.03, 1.81, and 1.29 [A] resolution, respectively. These results indicate that the EG-grid will be a powerful tool for high-throughput cryoEM data collection to accelerate high-resolution structural analysis of biological macromolecules.
  🖺 Full Text HTML: Epoxidized graphene grid for high- throughput high-resolution cryoEM structural analysis
• Multifactorial seroprofiling dissects the contribution of pre-existing human coronaviruses responses to SARS-CoV-2 immunity -

  Determination of SARS-CoV-2 antibody responses in the context of pre-existing immunity to circulating human coronavirus (HCoV) is critical to understanding protective immunity. Here we perform a multifactorial analysis of SARS- CoV-2 and HCoV antibody responses in pre-pandemic (N=825) and SARS-CoV-2-infected donors (N=389) using the custom-designed multiplex ABCORA assay. ABCORA seroprofiling, when combined with computational modeling, enables accurate definition of SARS-CoV-2 seroconversion and prediction of neutralization activity, and reveals intriguing interrelations with HCoV immunity. Specifically, higher HCoV antibody levels in SARS-CoV-2-negative donors suggest that preexisting HCoV immunity may provide protection against SARS-CoV-2 acquisition. In those infected, higher HCoV activity is associated with elevated SARS-CoV-2 responses, indicating cross-stimulation. Most importantly, HCoV immunity may impact disease severity, as patients with high HCoV reactivity are less likely to require hospitalization. Collectively, this evidence points to HCoV immunity promoting the rapid development of SARS-CoV-2-specific immunity, underscoring the importance of exploring cross-protective responses for comprehensive coronavirus prevention.

  🖺 Full Text HTML: Multifactorial seroprofiling dissects the contribution of pre-existing human coronaviruses responses to SARS-CoV-2 immunity
• Prosocial behavior promotes positive emotion during the COVID-19 pandemic -
  The COVID-19 pandemic has raised concerns about humans’ physical and mental well-being. In response, there has been an urgent “call to action” for psychological interventions that enhance positive emotion and psychological resilience. Prosocial behavior has been shown to effectively promote well-being, but is this strategy effective during a pandemic when ongoing apprehension for personal safety could acutely heighten self-focused concern? In two online pre-registered experiments (N =1,623) conducted during the early stage of pandemic (April 2020), we examined this question by randomly assigning participants to engage in other- or self-beneficial action. For the first time, we manipulated whether prosocial behavior was related to the source of stress (COVID-19): participants purchased COVID-19-related (personal protective equipment, PPE) or COVID-19-unrelated items (food/writing supplies) for themselves or someone else. Consistent with pre-registered hypotheses, prosocial (vs. non-prosocial or proself) behavior led to higher levels of self-reported positive affect, empathy and social connectedness. Notably, we also found that psychological benefits were larger when generous acts were unrelated to COVID-19 (vs. related to COVID-19). When prosocial and proself spending involved identical COVID-19 PPEs items, prosocial behavior’s benefits were detectable only on empathy and social connectedness, but not on post-task positive affect. These findings suggest that while there are boundary conditions to be considered, generous action offers one strategy to bolster well-being during the pandemic.
  🖺 Full Text HTML: Prosocial behavior promotes positive emotion during the COVID-19 pandemic
• Solitary and Joint Online Pornography Use During the First COVID-19 Lockdown in Portugal: Intrapersonal and Interpersonal Correlates -
  The onset of the COVID-19 pandemic forced several people into social isolation and research has shown a paradoxical effect on people’s sexual functioning. Some people experienced decreases in sexual desire and sexual satisfaction, whereas others experienced heightened sexual desire and made new additions to their sexual repertoire, including more online pornography use during the lockdown. Yet, studies failed to examine its interpersonal and intrapersonal correlates, distinguish between solitary and joint use, or explore differences between partnered and single people. We examined if changes in solitary or joint online pornography use since the lockdown were associated with sexual functioning, sexual satisfaction, perceived health, and sleep quality. We conducted an online cross-sectional study with convenience sampling in Portugal (N = 303 participants; 56.3% men; Mage = 31.32, SD = 10.55; 70.8% in a relationship) during May and July 2020. Partnered participants who reported increases in solitary online pornography use also reported decreases in their sex life quality. For partnered and single participants, increases in joint online pornography use were associated with increases in sex life quality. Single participants who reported increases in solitary online pornography use also perceived better health and sleep quality, and those who reported increases in joint online pornography use also reported more intimacy with casual partner(s) and better sleep quality. These findings suggest that online pornography was sometimes used as a sexual pleasure tool to connect with a stable or casual partner(s) in a time when social interactions were restricted.
  🖺 Full Text HTML: Solitary and Joint Online Pornography Use During the First COVID-19 Lockdown in Portugal: Intrapersonal and Interpersonal Correlates
• CAN DISASTERS IMPROVE THE TOURISM INDUSTRY? The role of normative, cognitive and relational expectations in shaping industry response to disaster-induced disruption -
  COVID-19 led to the hibernation of tourism activities globally, causing substantial economic loss and putting at risk the survival of many tourism businesses. At the same time, the reduction in travel activity led to an immediate and unprecedented reduction of global carbon emissions. Many academics argue that the tourism industry should be rebuilt in a more sustainable way post-COVID-19. Based on the sociological theory on response to disruption, the present study provides initial empirical evidence that long-lasting environmental benefits are unlikely to result from the pandemic. Recovery guidelines issued by the UNWTO and six member-based industry associations from different geographical locations and representing different types of tourism businesses form the basis of the empirical analysis. Member-based industry associations represent key information brokers during the pandemic; they convey information and advice to their member businesses. The result of the content analysis indicates the dominant impact of normative expectations, which exclusively focus on re-establishing the pre-COVID-19 status. While there is little indication that cognitive expectations – which view the pandemic as an opportunity to transform business operations to be more environmentally sustainable – will be leveraged. This stands in stark contrast to the collective hope that the tourism industry will become more sustainable after the pandemic.
  🖺 Full Text HTML: CAN DISASTERS IMPROVE THE TOURISM INDUSTRY? The role of normative, cognitive and relational expectations in shaping industry response to disaster-induced disruption
• SARS-CoV-2 RdRp is a versatile enzyme with proofreading activity and ability to incorporate NHC into RNA by using diphosphate form molnupiravir as a substrate -
  The coronavirus disease 2019 (COVID-19) has been ravaging throughout the world for almost two years and has severely impaired both human health and the economy. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs the viral RNA-dependent RNA polymerase (RdRp) complex for genome replication and transcription, making RdRp an appealing target for antiviral drug development. Although the structure of the RdRp complex has been determined, the function of RdRp has not been fully characterized. Here we reveal that in addition to RNA dependent RNA polymerase activity, RdRp also shows exoribonuclease activity and consequently proofreading activity. We observed that RdRp and nsp14-ExoN, when combined, exhibit higher proofreading activity compared to RdRp alone. Moreover, RdRp can recognize and utilize nucleoside diphosphate (NDP) as substrate to synthesize RNA and can also incorporate {beta}-d-N4-hydroxycytidine (NHC) into RNA while using diphosphate form molnupiravir as substrate.
  🖺 Full Text HTML: SARS-CoV-2 RdRp is a versatile enzyme with proofreading activity and ability to incorporate NHC into RNA by using diphosphate form molnupiravir as a substrate
• IFITM dependency of SARS-CoV-2 variants of concern -
  We have recently shown that a SARS-CoV-2 strain isolated in the Netherlands in February 2020 (NL-02-2020) hijacks interferon-induced transmembrane proteins, especially IFITM2, as entry cofactors for efficient infection. Here, we examined whether SARS-CoV-2 ‘variants of concern’ (VOCs), including the currently dominating delta variant, maintained the dependency on IFITMs for efficient replication. Depletion of IFITM2 reduced viral RNA production from 31- (B.1.1.7) to 755-fold (P.1). In comparison, silencing of IFITM1 had little effect, while knock-down of IFITM3 resulted in an intermediate phenotype. Strikingly, silencing of IFITM2 generally reduced infectious virus production in Calu-3 cells to near background levels. An antibody directed against the N-terminus of IFITM2 inhibited SARS-CoV-2 VOC replication in iPSC-derived alveolar epithelial type II cells. In conclusion, endogenously expressed IFITM proteins (especially IFITM2) are important cofactors for replication of genuine SARS-CoV-2 VOCs, including the Delta variant.
  🖺 Full Text HTML: IFITM dependency of SARS-CoV-2 variants of concern
• Global Mutational Sweep of SARS-CoV-2: from Chaos to Order -
  Analysis of large-scale genome sequences demonstrates the mutation of SARS-CoV-2 has been undergoing significant sweeps. Driven by emerging variants, global sweeps are accelerated and purified over time. This may prolong the pandemic with repeating epidemics, presenting challenges to the control and prevention of SARS-CoV-2.
  🖺 Full Text HTML: Global Mutational Sweep of SARS-CoV-2: from Chaos to Order
• Susceptibility of sheep to experimental co-infection with the ancestral lineage of SARS-CoV-2 and its alpha variant -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that has had significant impacts on human health and economies worldwide. SARS-CoV-2 is highly transmissible and the cause of coronavirus disease 2019 (COVID-19) in humans. A wide range of animal species have also been shown to be susceptible to SARS-CoV-2 infection by experimental and/or natural infections. Domestic and large cats, mink, ferrets, hamsters, deer mice, white-tailed deer, and non-human primates have been shown to be highly susceptible, whereas other species such as mice, dogs, pigs, and cattle appear to be refractory to infection or have very limited susceptibility. Sheep (Ovis aries) are a commonly farmed domestic ruminant that have not previously been thoroughly investigated for their susceptibility to SARS-CoV-2. Therefore, we performed in vitro and in vivo studies which consisted of infection of ruminant-derived cell cultures and experimental challenge of sheep to investigate their susceptibility to SARS-CoV-2. Our results showed that sheep-derived cell cultures support SARS-CoV-2 replication. Furthermore, experimental challenge of sheep demonstrated limited infection with viral RNA shed in nasal and oral swabs primarily at 1-day post challenge (DPC), and also detected in the respiratory tract and lymphoid tissues at 4 and 8 DPC. Sero-reactivity was also observed in some of the principal infected sheep but not the contact sentinels, indicating that transmission to co-mingled naive sheep was not highly efficient; hovewer, viral RNA was detected in some of the respiratory tract tissues of sentinel animals at 21 DPC. Furthermore, we used challenge inoculum consisting of a mixture of two SARS-CoV-2 isolates, representatives of the ancestral lineage A and the B.1.1.7-like alpha variant of concern (VOC), to study competition of the two virus strains. Our results indicate that sheep show low susceptibility to SARS-CoV-2 infection, and that the alpha VOC outcompeted the ancestral lineage A strain.
  🖺 Full Text HTML: Susceptibility of sheep to experimental co-infection with the ancestral lineage of SARS-CoV-2 and its alpha variant
• Microglia do not restrict SARS-CoV-2 replication following infection of the central nervous system of K18-hACE2 transgenic mice -
  Unlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not exhibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited anti-viral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, ~50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine (Cxcl9, Cxcl10, Ccl2, Ccl5 and Ccl19) and cytokine (Ifn-{lambda} and Tnf-) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Microglia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work demonstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease.
  🖺 Full Text HTML: Microglia do not restrict SARS-CoV-2 replication following infection of the central nervous system of K18-hACE2 transgenic mice
• The Delta variant of SARS-CoV-2 maintains high sensitivity to interferons in human lung cells -
  Interferons are a major part of the anti-viral innate defense system. Successful pathogens, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), need to overcome these defenses to establish an infection. Early induction of interferons (IFNs) protects against severe coronavirus disease 2019 (COVID-19). In line with this, SARS- CoV-2 is inhibited by IFNs in vitro, and IFN-based therapies against COVID-19 are investigated in clinical trials. However, SARS-CoV-2 continues to adapt to the human population resulting in the emergence of variants characterized by increased transmission fitness and/or decreased sensitivity to preventive or therapeutic measures. It has been suggested that the efficient spread of these so-called “Variants of Concern” (VOCs) may also involve reduced sensitivity to IFNs. Here, we examined whether the four current VOCs (Alpha, Beta, Gamma and Delta) differ in replication efficiency or IFN sensitivity from an early isolate of SARS-CoV-2. All viruses replicated in a human lung cell line and in iPSC-derived alveolar type II cells (iAT2). The Delta variant showed accelerated replication kinetics and higher infectious virus production compared to the early 2020 isolate. Replication of all SARS-CoV-2 VOCs was reduced in the presence of exogenous type I, II and III IFNs. On average, the Alpha variant was the least susceptible to IFNs and the Alpha, Beta and Gamma variants show increased resistance against type III IFN. Although the Delta variant has outcompeted all other variants in humans it remained as sensitive to IFNs as an early 2020 SARS-CoV-2 isolate. This suggests that increased replication fitness rather than IFN resistance may be a reason for its dominance. Our results may help to understand changes in innate immune susceptibility of VOCs, and inform clinical trials exploring IFN-based COVID-19 therapies.
  🖺 Full Text HTML: The Delta variant of SARS-CoV-2 maintains high sensitivity to interferons in human lung cells
• Tunneling nanotubes provide a novel route for SARS-CoV-2 spreading between permissive cells and to non-permissive neuronal cells. -
  SARS-CoV-2 entry into host cells is mediated by the binding of its spike glycoprotein to the angiotensin-converting enzyme 2 (ACE2) receptor, highly expressed in several organs, but very low in the brain. The mechanism through which SARS-CoV-2 infects neurons is not understood. Tunneling nanotubes (TNTs), actin-based intercellular conduits that connect distant cells, allow the transfer of cargos, including viruses. Here, we explored the neuroinvasive potential of SARS-CoV-2 and whether TNTs are involved in its spreading between cells in vitro. We report that neuronal cells, not permissive to SARS-CoV-2 through an exocytosis/endocytosis dependent pathway, can be infected when co-cultured with permissive infected epithelial cells. SARS-CoV-2 induces TNTs formation between permissive cells and exploits this route to spread to uninfected permissive cells in co-culture. Correlative Cryo-electron tomography reveals that SARS-CoV-2 is associated with the plasma membrane of TNTs formed between permissive cells and virus-like vesicular structures are inside TNTs established both between permissive cells and between permissive and non-permissive cells. Our data highlight a potential novel mechanism of SARS-CoV-2 spreading which could serve as route to invade non-permissive cells and potentiate infection in permissive cells.
  🖺 Full Text HTML: Tunneling nanotubes provide a novel route for SARS-CoV-2 spreading between permissive cells and to non-permissive neuronal cells.
• BSG/CD147 and ACE2 receptors facilitate SARS-CoV-2 infection of human iPS cell-derived kidney podocytes -
  Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the Coronavirus disease 2019 (COVID-19), which was declared a pandemic by the World Health Organization (WHO) in March 2020. The disease has caused more than 5.1 million deaths worldwide. While cells in the respiratory system are frequently the initial target for SARS-CoV-2, clinical studies suggest that COVID-19 can become a multi-organ disease in the most severe cases. Still, the direct affinity of SARS-CoV-2 for cells in other organs such as the kidneys, which are often affected in severe COVID-19, remains poorly understood. Method: In this study, we employed a human induced pluripotent stem (iPS) cell- derived model to investigate the affinity of SARS-CoV-2 for kidney glomerular podocytes. We studied uptake of the live SARS-CoV-2 virus as well as pseudotyped viral particles by human iPS cell derived podocytes using qPCR, western blot, and immunofluorescence. Global gene expression and qPCR analyses revealed that human iPS cell-derived podocytes express many host factor genes (including ACE2, BSG/CD147, PLS3, ACTR3, DOCK7, TMPRSS2, CTSL CD209, and CD33) associated with SARS-CoV-2 binding and viral processing. Result: Infection of podocytes with live SARS-CoV-2 or spike-pseudotyped lentiviral particles revealed viral uptake by the cells at low Multiplicity of Infection (MOI of 0.01) as confirmed by RNA quantification and immunofluorescence studies. Our results also indicate that direct infection of human iPS cell- derived podocytes by SARS-CoV-2 virus can cause cell death and podocyte foot process retraction, a hallmark of podocytopathies and progressive glomerular diseases including collapsing glomerulopathy observed in patients with severe COVID-19 disease. Additionally, antibody blocking experiments identified BSG/CD147 and ACE2 receptors as key mediators of spike binding activity in human iPS cell-derived podocytes. Conclusion: These results show that SARS-CoV-2 can infect kidney glomerular podocytes in vitro. These results also show that the uptake of SARS-CoV-2 by kidney podocytes occurs via multiple binding interactions and partners, which may underlie the high affinity of SARS-CoV-2 for kidney tissues. This stem cell-derived model is potentially useful for kidney-specific antiviral drug screening and mechanistic studies of COVID-19 organotropism.
  🖺 Full Text HTML: BSG/CD147 and ACE2 receptors facilitate SARS-CoV-2 infection of human iPS cell-derived kidney podocytes

From Clinical Trials

• 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
  Sponsor:  
  Hoffmann-La Roche
  Suspended

• Mesenchymal Stem Cell Secretome In Severe Cases of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: Injection of secretome - mesenchymal stem cell;   Other: Placebo;   Drug: Standard treatment of Covid-19
  Sponsor:   Indonesia University
  Completed

• Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for Mild-to-Moderate COVID-19: A Phase II Clinical Trial - Condition:   COVID-19
  Intervention:   Drug: ExoFlo
  Sponsor:   Direct Biologics, LLC
  Recruiting

• The South Proxa-Rescue AndroCoV Trial Against COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Proxalutamide;   Drug: Placebo
  Sponsors:   Corpometria Institute;   Hospital da Brigada Militar de Porto Alegre, Porto Alegre, Brazil;   Hospital Arcanjo Sao Miguel, Gramado, Brazil;   Hospital Unimed Chapeco, Chapeco, Brazil
  Completed

• Vitamin D Supplementation and Clinical Improvement in COVID-19 - Condition:   COVID-19
  Interventions:   Dietary Supplement: Vitamin D3 10000 IU;   Dietary Supplement: Vitamin D3 1000 IU
  Sponsor:   Bumi Herman
  Completed

• Feasibility Pilot Clinical Trial of Omega-3 Supplement vs. Placebo for Post Covid-19 Recovery Among Health Care Workers - Condition:   COVID-19
  Interventions:   Drug: Omega-3 (EPA+DHA);   Drug: Placebo
  Sponsor:   Hackensack Meridian Health
  Not yet recruiting

• Adding Colchicine to Tocilizumab in Patients With Severe COVID-19 Pneumonia. - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Colchicine
  Sponsor:  
  Hamad Medical Corporation
  Recruiting

• Controlled Trial of Angiotensin Receptor Blocker (ARB) & Chemokine Receptor Type 2 (CCR2) Antagonist for the Treatment of COVID-19 - Conditions:   COVID-19;   SARS-CoV2 Infection
  Interventions:   Drug: Candesartan Cilexetil;   Drug: Repagermanium;   Drug: Candesartan Placebo;   Drug: Repagermanium Placebo
  Sponsors:  
  University of Sydney;   The George Institute for Global Health, India
  Not yet recruiting

• Partnerships to Address COVID-19 Inequities - Condition:   COVID-19
  Interventions:   Behavioral: Crowdsourced campaign package;   Behavioral: Standard information
  Sponsor:   Duke University
  Not yet recruiting

• Study to Evaluate the inHaled Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) On the Protective-Efficacy in Adults (SeiHOPE) - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 vaccine (adenovirus type 5 vector) for Inhalation (Ad5-nCoV-IH);   Biological: Placebo
  Sponsors:   CanSino Biologics Inc.;   Beijing Institute of Biotechnology
  Not yet recruiting

• Pharmacokinetics, Pharmacodynamics, and Safety of Single-dose Sotrovimab in High-risk Pediatric Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Intervention:   Biological: Sotrovimab
  Sponsors:  
  GlaxoSmithKline;   Vir Biotechnology, Inc.
  Not yet recruiting

• PREVENT-COVID-19: A Q-Griffithsin Intranasal Spray - Condition:   COVID-19 Prevention
  Interventions:   Drug: Q-Griffithsin;   Other: Placebo
  Sponsors:   Kenneth Palmer;   United States Department of Defense
  Recruiting

• the Safety and Efficacy of Meplazumab in Patients With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Meplazumab for Injection;   Drug: Sterile normal saline (0.9%)
  Sponsor:   Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
  Not yet recruiting

• Health Information Technology for COVID-19 Testing in Schools (SCALE-UP Counts) - Condition:   COVID-19
  Interventions:   Behavioral: Text Messaging (TM);   Behavioral: Text Messaging + Health Navigation (TM+HN)
  Sponsors:   University of Utah;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  Not yet recruiting

• Covid-19 Pandemic and Use of Video Laryngoscopy - Condition:   COVID-19 Pneumonia
  Interventions:   Device: Videolaryngoscope;   Device: Macintosh Laryngoscope
  Sponsor:   Van Bölge Eğitim ve Araştırma Hastanesi
  Recruiting

From PubMed

• Ficus hirta Vahl. promotes antioxidant enzyme activity under ammonia stress by inhibiting miR-2765 expression in Penaeus vannamei - Ficus hirta Vahl. has been reported to have hepatoprotective, antitumor, antibacterial functions, and is used to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Ammonia nitrogen is one of the most common environmental stress factors in aquaculture. Long-term exposure to high concentrations of ammonia nitrogen can induce oxidative stress and increase the risk of infections. However, whether Ficus hirta Vahl. has effect on ammonia nitrogen stress is unclear. In present study we…

• SARS-CoV-2 may affect the immune response via direct inhibition of T cell receptor: Mechanistic hypothesis and rationale - During co-evolution with their hosts, many viruses have evolved a membrane fusion mechanism to facilitate host cell entry. Examples are human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2). These viruses can also infect immune cells (e.g., T cells), providing one of the possible mechanisms for the T cell lymphopenia observed in patients with these infections. Previously, we hypothesized and confirmed in vivo that like…

• Peptides derived from the SARS-CoV-2 receptor binding motif bind to ACE2 but do not block ACE2-mediated host cell entry or pro-inflammatory cytokine induction - SARS-CoV-2 viral attachment and entry into host cells is mediated by a direct interaction between viral spike glycoproteins and membrane bound angiotensin-converting enzyme 2 (ACE2). The receptor binding motif (RBM), located within the S1 subunit of the spike protein, incorporates the majority of known ACE2 contact residues responsible for high affinity binding and associated virulence. Observation of existing crystal structures of the SARS-CoV-2 receptor binding domain (SRBD)-ACE2 interface,…

• Nsp1 of SARS-CoV-2 stimulates host translation termination - Nsp1 of SARS-CoV-2 regulates the translation of host and viral mRNAs in cells. Nsp1 inhibits host translation initiation by occluding the entry channel of the 40S ribosome subunit. The structural study of the Nsp1-ribosomal complexes reported post-termination 80S complex containing Nsp1, eRF1 and ABCE1. Considering the presence of Nsp1 in the post- termination 80S ribosomal complex, we hypothesized that Nsp1 may be involved in translation termination. Using a cell- free translation system and…

• Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin - The struggle to control the COVID-19 pandemic is made challenging by the emergence of virulent SARS-CoV-2 variants. To gain insight into their replication dynamics, emergent Alpha (A), Beta (B) and Delta (D) SARS-CoV-2 variants were assessed for their infection performance in single variant- and co-infections. The effectiveness of thapsigargin (TG), a recently discovered broad-spectrum antiviral, against these variants was also examined. Of the 3 viruses, the D variant exhibited the highest…

• High-Throughput Virtual Screening and Validation of a SARS-CoV-2 Main Protease Noncovalent Inhibitor - Despite the recent availability of vaccines against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the search for inhibitory therapeutic agents has assumed importance especially in the context of emerging new viral variants. In this paper, we describe the discovery of a novel noncovalent small-molecule inhibitor, MCULE-5948770040, that binds to and inhibits the SARS-Cov-2 main protease (M^(pro)) by employing a scalable high-throughput virtual screening (HTVS) framework and a targeted…

• Clinical Antiviral Drug Arbidol Inhibits Infection by SARS-CoV-2 and Variants through Direct Binding to the Spike Protein - Arbidol (ARB) is a broad-spectrum antiviral drug approved in Russia and China for the treatment of influenza. ARB was tested in patients as a drug candidate for the treatment at the early onset of COVID-19 caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite promising clinical results and multiple ongoing trials, preclinical data are lacking and the molecular mechanism of action of ARB against SARS-CoV-2 remains unknown. Here, we demonstrate that ARB binds to…

• Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury - CONCLUSION: These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases.

• The role of microRNAs in solving COVID-19 puzzle from infection to therapeutics: A mini-review - Nowadays, one of the major global health concerns is coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though numerous treatments and vaccines to combat this virus are currently under development, the detailed molecular mechanisms underlying the pathogenesis of this disease are yet to be elucidated to design future therapeutic tools against SARS-CoV-2 variants. MicroRNAs (miRNAs) are small (20-24 nucleotides),…

• Contribution of autophagy machinery factors to HCV and SARS-CoV-2 replication organelle formation - Positive-strand RNA viruses replicate in close association with rearranged intracellular membranes. For hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), these rearrangements comprise endoplasmic reticulum (ER)-derived double membrane vesicles (DMVs) serving as RNA replication sites. Cellular factors involved in DMV biogenesis are poorly defined. Here, we show that despite structural similarity of viral DMVs with autophagosomes, conventional macroautophagy…

• IMPACT of PCSK9 inhibition on clinical outcome in patients during the inflammatory stage of the SARS-COV-2 infection: Rationale and protocol of the IMPACT-SIRIO 5 study - No abstract

• Interleukin-1 blocking agents as promising strategy for prevention of anticancer drug-induced cardiotoxicities: possible implications in cancer patients with COVID-19 - Cytokines in cardiac tissue plays a key role in progression of cardiometabolic diseases and cardiotoxicity induced by several anticancer drugs. Interleukin-1β is one on the most studied regulator of cancer progression, survival and resistance to anticancer treatments. Recent findings indicate that interleukin1-β exacerbates myocardial damages in cancer patients treated with chemotherapies and immune check-point inhibitors. Interleukin1-β blocking agent canakinumab reduces major adverse…

• All hands on deck: SARS-CoV-2 proteins that block early anti-viral interferon responses - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is responsible for the current pandemic coronavirus disease 2019 (COVID-19). Like other pathogens, SARS-CoV-2 infection can elicit production of the type I interferon (IFN) cytokines by the innate immune response. A rapid and robust type I and III IFN response can curb viral replication and improve clinical outcomes of SARS-CoV-2 infection. To effectively replicate in the host, SARS-CoV-2 has evolved mechanisms for evasion of…

• Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells - Currently available SARS-CoV-2 therapeutics are targeted towards moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected patients with no or mild symptoms. While vaccines have demonstrated protective efficacy, vaccine hesitancy and logistical distribution challenges will delay their ability to end the pandemic. Hence, there is a need for rapidly translatable, easy-to-administer-therapeutics, that can prevent SARS-CoV-2 disease…

• Antiviral and cytotoxic effects of a traditional drug KanthaRasaVillai with a cocktail of metallic nanoparticles - CONCLUSION: The anticancer and antiviral properties in the ancient herbomineral drug with a cocktail of metal nanoparticles acknowledge the traditional medical practice as a pioneering approach for present-day ailments. However, the study concludes that the use of KRV depends on safety dosage and genuine preparation as described by ancient saints.

From Patent Search

• A DOORBELL SYSTEM FOR MONITORING AND RECORDING A PHYSIOLOGICAL DATA OF A PERSON - AbstractTitle: A doorbell system for monitoring and recording a physiological data of a person The present invention provides a doorbell system 500 for monitoring and recording a physiological data of a person. The doorbell system 500 having a transmitter module 100 and a receiving module 200. The transmitter module 100 is having a TOF sensor module 110, an ultrasound detector 120, and an infrared detector 130. Further, a speech recognition system 150, a facial recognition system 160, and a temperature detector 190 are provided for recognizing speech, face, and temperature of the person by comparing pre-stored data. A controlling module 180 is set with a predefined commands for communicating with the transmitter module 100 and receiving module 200. The collected facial and speech data is compared and matched with the pre-stored data then the temperature detector 190 triggers and the door opens when the captured body temperature of the person is matched within the predefined range of temperature.Figure 1 - link

• A study of contemporary trends in investing patterns, household savings, and economic investment. - Because household savings and household investments are intertwined and interdependent, they are discussed briefly in this paper. Household savings account for more than half of a country’s capital formation, which fluctuates due to a variety of economic factors such as inflation and interest rates. Households should gradually shift their savings and investments from physical assets to financial assets to avoid a sudden change in wealth. They should also save and invest using a variety of platforms. Trends in investing and saving will be easier to track and measure this way. This year’s domestic saving rate in India is 2.3 percent lower than last year’s and 1.2 percent lower than the year before. Since 2011, general domestic savings have been steadily declining, with the trend continuing into the following year. According to official data, the GDP in 2020 shrank by 23.9%, the least in previous years and the least since the Covid-19 pandemic in previous years. As a result, the information presented in this paper is drawn from and evaluated from other sources - link

• Use of Diminazene Aceturate, Xanthenone, ACE 2 activators or analogs for the Treatment and therapeutic use of COVID-19 on human patients. - - link

• ACTIVE RIDER SAFETY SYSTEM FOR TWO WHEELERS - The present invention relates to an active rider safety system for two wheelers comprising, a protective case equipped by a user for riding, where the case is integrated with multiple piezoelectric sensor that determines fastening of the case by user, a processing unit linked to the sensor, where the unit detects absence of case upon fetching data from the sensor below a threshold value and thereby terminates operation of ignition by stopping a coupled motor operated via a radio frequency module, an alcohol detection sensor that detects presence of alcohol and send data to processing unit, a temperature sensor that measures temperature of the user, an accelerometer sensor that activates upon ignition us tuned on to determine presence of a crash and a navigation module that via communication module sends location of user to pre saved users and concerned authorities. - link

• Anti-SARS-CoV-2 antibodies and uses thereof I - - link

• Anti-SARS-CoV-2 antibodies and uses thereof II - - link

• Secured Health monitoring system using cloud computing - As used in public health surveillance, the invention generally relates to remote health monitoring systems with cloud computing. This is particularly relevant about a multi-user remote health monitoring system that can detect and gather data from healthcare professionals on the ground and systems in laboratories and hospitals to help the public health sector. It is possible to utilize the system for tracking, monitoring, and collecting patient data and for querying and collecting more information on the health of the people. - link

• SPIRAL GROOVES SQUEEZER - The present invention relates to squeezer that extracts the most of the juice or pulp from the citrus fruits like lemon, orange, etc. because of its design. The present invention works on the principle of reamer having left hand spiral. In general, Left hand spiral reamers have the tendency to push chips and coolant in front of the cut, pushing coolant into the hole and the reamer back out of the hole. The concept of the left hand spiral is used the subject squeezer to design the groves of squeezer to get maximum juice and to help prevent grabbing and binding of the fruit. It will release all the juice extracted from the fruit and will also be easy to remove the waste fruit skin from squeezer. - link

• 基于拉曼光谱的新型冠状病毒核酸检测试剂盒及方法 - 本发明公开了一种基于拉曼光谱的新型冠状病毒核酸检测试剂盒及方法，所述试剂盒包括正向引物，和纳米银针SERS基底，所述纳米银针SERS基底由5’端有巯基修饰的反向引物和纳米银针共价连接而得。其检测方法为：先采集纳米银针SERS基底的拉曼光谱信号；在包含待检测样品的反应溶液中插入所述纳米银针SERS基底，恒温扩增；取出纳米银针SERS基底，采集拉曼光谱信号，检测两次拉曼光谱信号的位移差异。相比起根据拉曼峰强度定量检测核酸的方法，本发明的新型冠状病毒核酸检测方法可以实现定性检测核酸，检测方法更简单、更准确、更可靠。 - link

• Infektionsschutz-Ausrüstung und das ihr zugrundeliegende System -

  Antivirusausrüstung, hergestellt aus einem mehrschichtigen Fasermaterial und ausgestattet mit Bindungen und einem antiviral wirkenden Element, das sich dadurch auszeichnet, dass das antiviral wirkende Element mindestens eine Gewebeschicht enthält, die mit dem Aerosol einer Emulsion bearbeitet wurde, das eine Aprotinin-Lösung enthält.

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