Covid-19 Sentry

Contents

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

From Preprints

• Making Visible the Invisible Work of Scientists during the COVID-19 Pandemic -
  Despite the perceptibility of the effects they impart on their hosts, the most incredible capacity of viruses is in their invisibility. Invisibility is the most frightening side of the current pandemic, and invisible is also the work of the scientists striving to find a solution. This proposal presents a data visualization that aims to give visibility to those scientists working on COVID-19. Their scientific publications have been computationally analyzed and transformed into a relational structure based on lexical similarity. The result is a network of scientists whose proximity is given by their closeness in writing. An innovative visual method that hybridizes network visualizations and word clouds shows the scientists in a deep space, explorable through keywords. In such a space, individuals are situated according to their lexical similarity, and keywords are used to clarify their proximity. By zooming, the visualization reveals more information about scientists and their clusters. While a lot of visualizations during the pandemic focused on showing the spread of infection, causing anxiety among the readers, this visualization reveals the efforts of science in eradicating the virus. Making visible the enormous number of scientists working on COVID-19 research will contribute to coping more positively with the pandemic.
  🖺 Full Text HTML: Making Visible the Invisible Work of Scientists during the COVID-19 Pandemic
• Covid-19: acquired acute porphyria hypothesis -
  Pandemic Covid-19 pneumonia, of SARS-CoV-2 aetiology, is of global importance to health systems, national economies and individual civil liberties. Multiple therapeutic and prophylactic agents are currently undergoing clinical trial and, while progress towards a curative agent is promising, the principal limiting factor in public health emergency is time. A pre-existing licensed therapeutic would offer reprieve to international citizens currently enduring the adverse consequences of lockdown policies. This brief communication serves as an update on the initial version of the acquired acute porphyria hypothesis and advocates for direct testing of the hypothesis.
  🖺 Full Text HTML: Covid-19: acquired acute porphyria hypothesis
• Rosin Soap Exhibits Virucidal Activity -
  Chemical methods of virus inactivation are used routinely to prevent viral transmission in both a personal hygiene capacity but also in at-risk environments like hospitals. Several virucidal products exist, including hand soaps, gels and surface disinfectants. Resin acids, which can be derived from Tall oil produced from trees, have been shown to exhibit anti-bacterial activity. However, whether these products or their derivatives have virucidal activity is unknown. Here, we assessed the capacity of Rosin soap to inactivate a panel of pathogenic mammalian viruses in vitro. We show that Rosin soap can inactivate the human enveloped viruses: influenza A virus (IAV), respiratory syncytial virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For IAV, rosin soap could provide a 100,000-fold reduction in infectivity. However, Rosin soap failed to affect the non-enveloped encephalomyocarditis virus (EMCV). The inhibitory effect of Rosin soap against IAV infectivity was dependent on its concentration but not dependent on incubation time nor temperature. Together, we demonstrate a novel chemical inactivation method against enveloped viruses, which could be of use in preventing virus infections in certain settings.
  🖺 Full Text HTML: Rosin Soap Exhibits Virucidal Activity
• Comparison of Neutralizing Antibody Titers Elicited by mRNA and Adenoviral Vector Vaccine against SARS-CoV-2 Variants -
  The increasing prevalence of SARS-CoV-2 variants has raised concerns regarding possible decreases in vaccine efficacy. Here, neutralizing antibody titers elicited by mRNA-based and an adenoviral vector-based vaccine against variant pseudotyped viruses were compared. BNT162b2 and mRNA-1273-elicited antibodies showed modest neutralization resistance against Beta, Delta, Delta plus and Lambda variants whereas Ad26.COV2.S-elicited antibodies from a significant fraction of vaccinated individuals were of low neutralizing titer (IC50 <50). The data underscore the importance of surveillance for breakthrough infections that result in severe COVID-19 and suggest the benefit of a second immunization following Ad26.COV2.S to increase protection against the variants.
  🖺 Full Text HTML: Comparison of Neutralizing Antibody Titers Elicited by mRNA and Adenoviral Vector Vaccine against SARS- CoV-2 Variants
• Paradoxical Sex-Specific Patterns of Autoantibodies Response to SARS-CoV-2 Infection -

  Background. Amidst the millions of individuals affected directly by the pandemic, pronounced sex differences in the susceptibility and response to SARS-CoV-2 infection remain poorly understood. Emerging evidence has highlighted the potential importance of autoimmune activation in modulating not only the acute response but also recovery trajectories following SARS-CoV-2 exposure. Given that immune-inflammatory activity can be sex-biased in the setting of severe COVID-19 illness, we deliberately examined sex-specific autoimmune reactivity to SARS-CoV-2 in the absence of extreme clinical disease. Methods. We used a bead-based array containing over 90 autoantigens previously linked to a range of classic autoimmune diseases to assess autoantibody (AAB) titers in 177 participants. All participants had confirmed evidence of prior SARS-CoV-2 infection based on presence of positive anti-nucleocapsid IgG serology results (Abbott Diagnostics, Abbott Park, Illinois). We used multivariate analysis to determine whether sex-bias was associated with increased rates of AABs reactivity and symptom burden after SARS-CoV2 infection. Results. 82.4% of AABs reactivity was associated with being male compared to 17.6% with female. We found a diversity of AABs responses that exhibited sex- specific patterns of frequency distribution as well as associations with symptomatology and symptom burden. Conclusion. Our results reveal a remarkable sex-specific prevalence and selectivity of AAB responses to SARS-CoV-2. Further understanding of the nature of triggered and persistent AAB activation among men and women exposed to SARS-CoV-2 will be essential for developing effective interventions against immune-mediated sequelae of COVID-19.

  🖺 Full Text HTML: Paradoxical Sex-Specific Patterns of Autoantibodies Response to SARS-CoV-2 Infection
• Unveiling Mutation Effects on the Structural Dynamics of the Main Protease from SARS-CoV-2 with Hybrid Simulation Methods -
  In this article, we used a hybrid simulation method to sample the conformational space to characterize the structural dynamics and global motions of WT SARS-CoV-2 Mpro and 48 mutants, including several mutations that appear in P.1, B.1.1.7, B.1.351, B.1.525 and B.1.429+B.1.427 variants. Integrated Hybrid methods combining NMA and MD have been useful to study the correlation between the complex structural dynamics of macromolecules and their functioning mechanisms. Here, we applied this hybrid approach to elucidate the effects of mutation in the structural dynamics of SARS-CoV-2 Mpro, considering their flexibility, solvent accessible surface area analyses, global movements, and catalytic dyad distance. Furthermore, some mutants showed significant changes in their structural dynamics and conformation, which could lead to distinct functional properties.
  🖺 Full Text HTML: Unveiling Mutation Effects on the Structural Dynamics of the Main Protease from SARS-CoV-2 with Hybrid Simulation Methods
• Integrative multi-omics landscape of non-structural protein 3 of severe acute respiratory syndrome coronaviruses -
  The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently a global pandemic. Extensive investigations have been performed to study the clinical and cellular effects of SARS-CoV-2 infection. Mass spectrometry-based proteomics studies have revealed the cellular changes due to the infection and identified a plethora of interactors for all SARS-CoV-2 components, except for the longest non- structural protein 3 (NSP3). Here, we expressed the full-length NSP3 proteins of SARS-CoV and SARS-CoV-2 to investigate their unique and shared functions using multi-omics methods. We conducted interactome, phosphoproteome, ubiquitylome, transcriptome, and proteome analyses of NSP3-expressing cells. We found that NSP3 plays essential roles in cellular functions such as RNA metabolism and immune response such as NF-kB signal transduction. Interestingly, we showed that SARS-CoV-2 NSP3 has both endoplasmic reticulum and mitochondrial localizations. In addition, SARS-CoV-2 NSP3 is more closely related to mitochondrial ribosomal proteins, whereas SARS-CoV NSP3 is related to the cytosolic ribosomal proteins. In summary, our multi-omics studies of NSP3 enhance our understanding of the functions of NSP3 and offer valuable insights for the development of anti-SARS strategies.
  🖺 Full Text HTML: Integrative multi-omics landscape of non-structural protein 3 of severe acute respiratory syndrome coronaviruses
• Single-dose respiratory mucosal delivery of next-generation viral-vectored COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2 -
  The emerging SARS-CoV-2 variants of concern (VOC) increasingly threaten the effectiveness of current first- generation COVID-19 vaccines that are administered intramuscularly and are designed to only target the spike protein. There is thus a pressing need to develop next-generation vaccine strategies to provide more broad and long-lasting protection. By using adenoviral vectors (Ad) of human and chimpanzee origin, we developed Ad-vectored trivalent COVID-19 vaccines expressing Spike-1, Nucleocapsid and RdRp antigens and evaluated them following single-dose intramuscular or intranasal immunization in murine models. We show that respiratory mucosal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the three-arm immunity, consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells, and mucosal trained innate immunity. We further show that single-dose intranasal immunization provides robust protection against not only the ancestral strain of SARS-CoV-2, but also two emerging VOC, B.1.1.7 and B.1.351. Our findings indicate that single-dose respiratory mucosal delivery of an Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy against current and future VOC. This strategy has great potential to be used not only to boost first-generation vaccine-induced immunity but also to expand the breadth of protective T cell immunity at the respiratory mucosa.

• Dique Filipeia: A rehabilitation protocol for non-intubated COVID-19 in-hospital patients -

  Objective: The aim of this study was to evaluate the effectiveness of the Dique Filipeia rehabilitation protocol in patients with COVID-19 admitted to reference hospitals. Methods: This is an experimental study with COVID-19 patients admitted to the hospitals wards being considered eligible. The study outcomes were assessed between patients undergoing the rehabilitation protocol (Dique Filipeia group) and patients who did not receive the protocol (control group). The rehabilitation protocol consisted in classifying patients daily into four levels of severity through peripheral oxygen saturation. Severity was classified by the oxygen flow needed to maintain a saturation greater than or equal to the cut-off point of 93%. A standardized ventilatory support and functional rehabilitation exercises were performed for each severity level patient, followed by an attempt to wean oxygen. Results: A total of 727 patients were analyzed in the study. The Dique Filipeia group presented a lower total (132.7 vs 307.0 m3/patient; effect size 1.73) and daily (2.9 vs 6.8 m3/day/patient; effect size 1.46) oxygen expenditure than the control group. The Dique Filipeia patients presented higher hospital discharge (64.9 vs 35.4%; effect size 3.46) and lower length of stay (15.8 vs 29.1 days; effect size 3.47) than the control group. The Dique Filipeia group patients, who were demanding oxygen therapy, were using 6.2 L/min of oxygen at day 1. There was a statistically significant reduction from day 2 (p = 0.0001) and oxygen flow was reduced below 1L/min after day 7. Conclusions: The implementation of a standardized rehabilitation protocol reduced oxygen expenditure, increased hospital discharge and reduced the length of hospital stay. Dique Filipeia is a practical, feasible and safe protocol.

  🖺 Full Text HTML: Dique Filipeia: A rehabilitation protocol for non-intubated COVID-19 in-hospital patients
• SARS-CoV-2 Spike Pseudoviruses: A Useful tool to study virus entry and address emerging neutralization escape phenotypes -
  SARS-CoV-2 genetic variants are emerging around the globe. Unfortunately, several SARS-CoV-2 variants, especially, variants of concern (VOC) are less susceptible to neutralization by the convalescent and post-vaccination sera, raising concerns of increased disease transmissibility and severity. Recent data suggests the SARS-CoV-2 neutralizing anti-body levels as a good correlate of vaccine mediated protection. However, currently used BSL3 based virus micro-neutralization (MN) assays are more laborious, time consuming and expensive, underscoring the need for BSL2 based, cost effective neutralization assays against SARS-CoV-2 variants. In light of this unmet need, we have developed a BSL2 pseudovirus based neutralization assay (PBNA) in cells expressing Angiotensin Converting Enzyme-2 (ACE2) receptor for SARS-CoV-2. The assay is reproducible (R2=0.96), demonstrates a good dynamic range and high sensitivity. Our data suggests that the biological Anti-SARS-CoV-2 research reagents such as NIBSC 20/130 show lower neutralization against B.1.351 RSA and B1.1.7 UK VOC, whereas a commercially available monoclonal antibody MM43 retains activity against both these variants. SARS-CoV-2 Spike Pseudovirus based neutralization assays for VOC would be useful tools to measure the neutralization ability of candidate vaccines in both preclinical models and clinical trials and further help develop effective prophylactic countermeasures against emerging neutralization escape phenotypes.
  🖺 Full Text HTML: SARS- CoV-2 Spike Pseudoviruses: A Useful tool to study virus entry and address emerging neutralization escape phenotypes
• Susceptibilities of human ACE2 genetic variants in coronavirus infection -
  The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in more than 1603 million cases worldwide and 3.4 million deaths (as of May 2021), with varying incidences and death rates among regions/ethnicities. Human genetic variation can affect disease progression and outcome, but little is known about genetic risk factors for SARS-CoV-2 infection. The coronaviruses SARS-CoV, SARS-CoV-2 and HCoV-NL63 all utilize the human protein angiotensin-converting enzyme 2 (ACE2) as the receptor to enter cells. We hypothesized that the genetic variability in ACE2 may contribute to the variable clinical outcomes of COVID-19. To test this hypothesis, we first conducted an in silico investigation of single- nucleotide polymorphisms (SNPs) in the coding region of ACE2 gene. We then applied an integrated approach of genetics, biochemistry and virology to explore the capacity of select ACE2 variants to bind coronavirus spike protein and mediate viral entry. We identified the ACE2 D355N variant that restricts the spike protein-ACE2 interaction and consequently limits infection both in vitro and in vivo. In conclusion, ACE2 polymorphisms could modulate susceptibility to SARS- CoV-2, which may lead to variable disease severity.
  🖺 Full Text HTML: Susceptibilities of human ACE2 genetic variants in coronavirus infection
• One mucosal administration of a live attenuated recombinant COVID-19 vaccine protects non-human primates from SARS- CoV-2 -
  Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. Vaccines are needed to control the disease and bring an end to the pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein, spike, for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live attenuated, recombinant human respiratory syncytial virus (RSV) expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing the peak shedding of SARS-CoV-2 in the nose by more than 200-fold. MV-014-212 elicited mucosal immunity in the nose and neutralizing antibodies in serum that exhibited cross neutralization against two virus variants of concern. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in phase I clinical trials as a single-dose intranasal COVID-19 vaccine.
  🖺 Full Text HTML: One mucosal administration of a live attenuated recombinant COVID-19 vaccine protects non-human primates from SARS-CoV-2
• Molecular evolution and structural analyses of the spike glycoprotein from Brazilian SARS-CoV-2 genomes: the impact of the fixation of selected mutations -
  The COVID-19 pandemic caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached by July 2021 almost 200 million cases and more than 4 million deaths worldwide since its beginning in late 2019, leading to enhanced concern in the scientific community and the general population. One of the most important pieces of this host- pathogen interaction is the spike protein, which binds to the human Angiotensin-converting enzyme 2 (hACE2) cell receptor, mediates the membrane fusion and is the major target of neutralizing antibodies against SARS-CoV-2. The multiple amino acid substitutions observed in this region, specially in the Receptor Binding Domain (RBD), mainly after almost one year of its emergence (late 2020), have enhanced the hACE2 binding affinity and led to several modifications in the mechanisms of SARS-CoV-2 pathogenesis, improving the viral fitness and/or promoting immune evasion, with potential impact in the vaccine development. In this way, the present work aimed to evaluate the effect of positively selected mutations fixed in the Brazilian SARS-CoV-2 lineages and to check for mutational evidence of coevolution. Additionally, we evaluated the impact of selected mutations identified in some of the VOC and VOI lineages (C.37, B.1.1.7, P.1, and P.2) of Brazilian samples on the structural stability of the spike protein, as well as their possible association with more aggressive infection profiles by estimating the binding affinity in the RBD-hACE2 complex. We identified 48 sites under selective pressure in Brazilian spike sequences, 17 of them with the strongest evidence by the HyPhy tests, including VOC related mutation sites 138, 142, 222, 262, 484, 681, and 845, among others. The coevolutionary analysis identified a number of 28 coevolving sites that were found not to be conditionally independent, such as the couple E484K - N501Y from P.1 and B.1.351 lineages. Finally, the molecular dynamics and free energy estimates showed the structural stabilizing effect and the higher impact of E484K for the improvement of the binding affinity between the spike RBD and the hACE2 in P.1 and P.2 lineages, as well as the stabilizing and destabilizing effects for the positively selected sites.
  🖺 Full Text HTML: Molecular evolution and structural analyses of the spike glycoprotein from Brazilian SARS-CoV-2 genomes: the impact of the fixation of selected mutations
• ACE2 binding is an ancestral and evolvable trait of sarbecoviruses -
  Two different sarbecoviruses have caused major human outbreaks in the last two decades. Both these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 via the spike receptor-binding domain (RBD). However, binding to ACE2 orthologs from humans, bats, and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses. Here, we use high-throughput assays to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologs. We find that ACE2 binding is an ancestral trait of sarbecovirus RBDs that has subsequently been lost in some clades. Furthermore, we demonstrate for the first time that bat sarbecoviruses from outside Asia can bind ACE2. In addition, ACE2 binding is highly evolvable: for many sarbecovirus RBDs there are single amino-acid mutations that enable binding to new ACE2 orthologs. However, the effects of individual mutations can differ markedly between viruses, as illustrated by the N501Y mutation which enhances human ACE2 binding affinity within several SARS-CoV-2 variants of concern but severely dampens it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening consideration of the range of sarbecoviruses with spillover potential.
  🖺 Full Text HTML: ACE2 binding is an ancestral and evolvable trait of sarbecoviruses
• Mutation-induced Changes in the Receptor-binding Interface of the SARS-CoV-2 Delta Variant B.1.617.2 and Implications for Immune Evasion -
  While the vaccination efforts against SARS-CoV-2 infections are ongoing worldwide, new genetic variants of the virus are emerging and spreading. Following the initial surges of the Alpha (B.1.1.7) and the Beta (B.1.351) variants, a more infectious Delta variant (B.1.617.2) is now surging, further deepening the health crises caused by the pandemic. The sharp rise in cases attributed to the Delta variant has made it especially disturbing and is a variant of concern. Fortunately, current vaccines offer protection against known variants of concern, including the Delta variant. However, the Delta variant has exhibited some ability to dodge the immune system as it is found that neutralizing antibodies from prior infections or vaccines are less receptive to binding with the Delta spike protein. Here, we investigated the structural changes caused by the mutations in the Delta variant’s receptor-binding interface and explored the effects on binding with the ACE2 receptor as well as with neutralizing antibodies. We find that the receptor-binding beta-loop- beta motif adopts an altered but stable conformation causing separation in some of the antibody binding epitopes. Our study shows reduced binding of neutralizing antibodies and provides a possible mechanism for the immune evasion exhibited by the Delta variant.
  🖺 Full Text HTML: Mutation-induced Changes in the Receptor-binding Interface of the SARS-CoV-2 Delta Variant B.1.617.2 and Implications for Immune Evasion

From Clinical Trials

• COVID-19 Vaccinations With a Sweepstakes - Condition:   Covid19
  Intervention:   Behavioral: Philly Vax Sweepstakes
  Sponsors:  
  University of Pennsylvania;   Philadelphia Department of Public Health
  Active, not recruiting

• Covid-19 Virtual Recovery Study - Condition:   Covid19
  Interventions:   Behavioral: Strength RMT;   Behavioral: Strength RMT and nasal breathing;   Behavioral: Endurance RMT;   Behavioral: Endurance RMT and nasal breathing;   Behavioral: Low dose RMT
  Sponsor:   Mayo Clinic
  Not yet recruiting

• A Study of PF-07321332/Ritonavir in Nonhospitalized High Risk Adult Participants With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: PF-07321332;   Drug: Ritonavir;   Drug: Placebo
  Sponsor:   Pfizer
  Not yet recruiting

• Building Resiliency and Vital Equity (BRAVE) Project: Understanding Native Americans’ Perceptions/Beliefs About COVID-19 Testing and Vaccination Study - Condition:   Covid19 Virus Infection
  Intervention:   Behavioral: Protect Your Elders Campaign
  Sponsors:   North Carolina Central University;   Lumbee Tribe of North Carolina;   University of North Carolina at Pembroke
  Recruiting

• A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adolescents - Condition:   Covid19 Vaccine
  Interventions:   Biological: MVC-COV1901(S protein with adjuvant);   Biological: MVC-COV1901(Saline)
  Sponsor:   Medigen Vaccine Biologics Corp.
  Not yet recruiting

• Study on Sequential Immunization of Inactivated COVID-19 Vaccine and Recombinant COVID-19 Vaccine (Ad5 Vector) - Condition:   COVID-19
  Interventions:   Biological: Recombinant SARS-CoV-2 Ad5 vectored vaccine;   Biological: Inactive SARS-CoV-2 vaccine (Vero cell)
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   CanSino Biologics Inc.
  Not yet recruiting

• Efficacy of Amantadine Treatment in COVID-19 Patients - Condition:   Patients With Moderate or Severe COVID-19
  Intervention:   Drug: Amantadine
  Sponsors:   Noblewell;   Medical Research Agency (ABM);   Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
  Recruiting

• Internet-based Multidisciplinary Rehabilitation for Longterm COVID-19 Syndrome - Condition:   Long COVID-19
  Intervention:   Behavioral: Multidisciplinary Rehabilitation
  Sponsors:   Danderyd Hospital;   St Göran Hospital, Stockholm
  Recruiting

• Enabling Family Physicians to Reduce Vaccine Hesitancy and Increase Covid-19 Vaccine Uptake - Conditions:   Covid19;   COVID-19 Vaccine
  Interventions:  
  Behavioral: Tailored COVID-19 vaccine messages;   Other: Other health messages
  Sponsors:  
  Hopital Montfort;   Public Health Agency of Canada (PHAC);   Eastern Ontario Health Unit
  Not yet recruiting

• A Different Use of The Aerosol Box in COVID-19 Patients; Internal Jugular Vein Cannulation - Condition:   COVID-19 Pneumonia
  Intervention:   Procedure: Internal jugular vein cannulation
  Sponsor:   Bakirkoy Dr. Sadi Konuk Research and Training Hospital
  Completed

• Reconditioning Exercise for COVID-19 Patients Experiencing Residual sYmptoms - Condition:   Covid19
  Intervention:   Other: Exercise Therapy
  Sponsor:  
  Wake Forest University Health Sciences
  Not yet recruiting

• Lipid Emulsion Infusion and COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: SMOFlipid;   Other: 0.9% saline
  Sponsor:   Assiut University
  Recruiting

• Short Term, High Dose Vitamin D Supplementation in Moderate to Severe COVID-19 Disease - Condition:   Covid19
  Intervention:   Drug: cholecalciferol 6 lakh IU
  Sponsor:  
  Postgraduate Institute of Medical Education and Research
  Not yet recruiting

• Immunogenicity and Safety of an Inactivated COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Biological: Inactivated COVID-19 Vaccine;   Biological: 23-valent pneumococcal polysaccharide vaccine;   Biological: Inactivated Hepatitis A Vaccine
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Evaluation of the RD-X19 Treatment Device in Individuals With Mild to Moderate COVID-19 - Condition:   COVID19
  Interventions:   Device: RD-X19;   Device: Sham
  Sponsor:  
  EmitBio Inc.
  Recruiting

From PubMed

• Molecular Mechanisms of Palmitic Acid Augmentation in COVID-19 Pathologies - The coronavirus disease 2019 (COVID-19) pandemic has claimed over 2.7 million lives globally. Obesity has been associated with increased severity and mortality of COVID-19. However, the molecular mechanisms by which obesity exacerbates COVID-19 pathologies are not well-defined. The levels of free fatty acids (FFAs) are elevated in obese subjects. This study was therefore designed to examine how excess levels of different FFAs may affect the progression of COVID-19. Biological molecules…

• Regulation of Mindfulness-Based Music Listening on Negative Emotions Related to COVID-19: An ERP Study - The current study aimed to explore the behavioral and neural correlates of mindfulness-based music listening regulation of induced negative emotions related to COVID-19 using the face-word Stroop task. Eighty-five young adults visited the laboratory and were randomly assigned to three groups: a calm music group (CMG: n = 28), a happy music group (HMG: n = 30), and a sad music group (SMG: n = 27). Negative emotions were induced in all participants using a COVID-19 video, followed by the music…

• Broad sarbecovirus neutralization by a human monoclonal antibody - The recent emergence of SARS-CoV-2 variants of concern (VOC)^(1-10) and the recurrent spillovers of coronaviruses^(11,12) in the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here, we describe a human monoclonal antibody (mAb), designated S2X259, recognizing a highly conserved cryptic receptor-binding domain (RBD) epitope and cross-reacting with spikes from all…

• Structure-Based Discovery of Novel Nonpeptide Inhibitors Targeting SARS-CoV-2 M(pro) - The continual spread of novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), posing a severe threat to the health worldwide. The main protease (M^(pro), alias 3CL^(pro)) of SARS-CoV-2 is a crucial enzyme for the maturation of viral particles and is a very attractive target for designing drugs to treat COVID-19. Here, we propose a multiple conformation-based virtual screening strategy to discover inhibitors that can target SARS-CoV-2…

• Lentil lectin derived from Lens culinaris exhibit broad antiviral activities against SARS-CoV-2 variants - The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern. S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for development of anti-SARS-CoV-2 strategies against variants. Here, we collected twelve plant-derived lectins with different carbohydrate specificity and…

• Efficient Inhibition of SARS-CoV-2 Using Chimeric oligonucleotides through RNase L Activation - Currently there is an urgent need to develop antiviral drugs and alleviate current COVID-19 pandemic. Although many candidates have been developed, we here designed and constructed chimeric oligonucleotides comprising a 2’-OMe modified antisense oligonucleotide and a 5’-phosphorylated 2’-5’ poly(A) 4 (4A 2-5 ) to degrade envelope and spike RNAs of SARS- CoV-2. The oligonucleotide was used for searching and recognizing target viral RNA sequence, and the conjugated 4A 2-5 was used for guided…

• The potential use of microRNAs as a therapeutic strategy for SARS-CoV-2 infection - Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, there is no effective therapeutic approach for treating SARS-CoV-2 infections. MicroRNAs (miRNAs) have been recognized to target the viral genome directly or indirectly, thereby inhibiting viral replication. Several studies have demonstrated that host miRNAs target different sites in SARS-CoV-2 RNA and constrain the production of essential viral proteins. Furthermore, miRNAs…

• SARS-CoV-2 M(pro) inhibition by a zinc ion: structural features and hints for drug design - Structural data on the SARS-CoV-2 main protease in complex with a zinc-containing organic inhibitor are already present in the literature and gave hints on the presence of a zinc binding site involving the catalytically relevant cysteine and histidine residues. In this paper, the structural basis of ionic zinc binding to the SARS-CoV-2 main protease has been elucidated by X-ray crystallography. The zinc binding affinity and its ability to inhibit the SARS-CoV-2 main protease have been…

• Renin Angiotensin System Inhibition as treatment for Covid-19? - No abstract

• The Strand-biased Transcription of SARS-CoV-2 and Unbalanced Inhibition by Remdesivir - SARS-CoV-2, a positive single-stranded RNA virus, causes the COVID-19 pandemic. During the viral replication and transcription, the RNA dependent RNA polymerase (RdRp) “jumps” along the genome template, resulting in discontinuous negative-stranded transcripts. Although the sense-mRNA architectures of SARS-CoV-2 were reported, its negative strand was unexplored. Here, we deeply sequenced both strands of RNA and found SARS-CoV-2 transcription is strongly biased to form the sense strand with…

• Reliable Estimation of CD8 T Cell Inhibition of In Vitro HIV-1 Replication - The HIV-1 viral inhibition assay (VIA) measures CD8 T cell-mediated inhibition of HIV replication in CD4 T cells and is increasingly used for clinical testing of HIV vaccines and immunotherapies. The VIA has multiple sources of variability arising from in vitro HIV infection and co-culture of two T cell populations. Here, we describe multiple modifications to a 7-day VIA protocol, the most impactful being the introduction of independent replicate cultures for both HIV infected-CD4 (HIV-CD4) and…

• High Dose Lopinavir/Ritonavir Does Not Lead to Sufficient Plasma Levels to Inhibit SARS-CoV-2 in Hospitalized Patients With COVID-19 - Background: Despite lopinavir/ritonavir (LPV/RTV) demonstrating in-vitro activity against SARS-CoV-2, large trials failed to show any net clinical benefit. Since SARS-CoV-2 has an EC50 of 16.4 μg/ml for LPV this could be due to inadequate dosing. Methods: COVID-19 positive patients admitted to the hospital who received high dose LPV/RTV were included. High dose (HD) LPV/RTV 200/50 mg was defined as four tablets bid as loading dose, then three tablets bid for up to 10 days. Trough plasma…

• Remdesivir Inhibits Tubulointerstitial Fibrosis in Obstructed Kidneys - Aim: Kidney impairment is observed in patients with COVID-19. The effect of anti-COVID-19 agent remdesivir on kidneys is currently unknown. We aimed to determine the effect of remdesivir on renal fibrosis and its downstream mechanisms. Methods: Remdesivir and its active nucleoside metabolite GS-441524 were used to treat TGF-β stimulated renal fibroblasts (NRK-49F) and human renal epithelial (HK2) cells. Vehicle or remdesivir were given by intraperitoneal injection or renal injection through the…

• The association of WTELS as a master motivator with higher executive functioning and better mental health - The goal is to test the validity of the "Will to exist-live and survive (WTELS) as a master motivator that activates executive functions. A sample of 262 adults administered different measures that included WTELS and executive functions. We conducted hierarchical regressions with working memory deficits (WMD) and inhibition deficits (ID) as dependent variables. We entered in the last steps resilience and WTELS as independent variables. We conducted path analysis with WTELS as independent…

• Our Words in a State of Emergency: Psychological-Linguistic Analysis of Utterances on the COVID-19 Situation in the Czech Republic - The study focuses on psychological-linguistic analysis of utterances provided by N = 2522 respondents aged 18-89 years in the period of March-May 2020, for the research of JUPSYCOR (Psychological Impacts of the Coronavirus Epidemic in the Czech Republic). The utterances relate to the interpretation of the state of emergency, the COVID-19 epidemic, and its subjectively perceived impacts. Simultaneously, the study examines the relationship between the analysed texts and the results of the SEHW…

From Patent Search

• A SYSTEM AND METHOD FOR COVID- 19 DIAGNOSIS USING DETECTION RESULTS FROM CHEST X- RAY IMAGES - - link

• Advanced Machine Learning System combating COVID-19 virus Detection, Spread, Prevention and Medical Assistance. - - link

• Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link

• 一种新型冠状病毒的mRNA疫苗 - 本发明公开了一种新型冠状病毒的mRNA疫苗。本发明提供的疫苗，其活性成分为mRNA，如序列表的序列6所示。本发明还保护TF‑RBD蛋白，如序列表的序列2所示。本发明的发明人通过一系列序列设计和序列优化得到了特异DNA分子，进一步构建了特异重组质粒，将特异重组质粒进行体外转录，可以得到多聚化TF‑RBD mRNA。进一步的，发明人制备了负载TF‑RBD mRNA的脂质纳米粒。本发明对于新型冠状病毒的防控具有重大的应用推广价值。 - link

• 新型冠状病毒B．1．1．7英国突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B．1．1．7英国突变株RBD的基因及其应用。本发明的新型冠状病毒B．1．1．7英国突变株RBD的基因，其核苷酸序列如SEQ ID NO.1或SEQ ID NO.6所示。本发明通过优化野生型新型冠状病毒B．1．1．7英国突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B．1．1．7英国突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B．1．1．7英国突变株RBD的基因更有利于用于制备新型冠状病毒疫苗。 - link

• SARS-CoV-2 anti-viral therapeutic - - link

• 一种基于联邦学习的多用户协同训练人流统计方法及系统 - 本发明提供一种基于联邦学习的多用户协同训练人流统计方法，旨在利用联邦学习框架搭建一个新颖的人群计数模型，达到让多用户多设备同时训练的目的。各个客户端利用图像数据集对图像分类网络进行本地训练以获取本地模型；在各经过至少一次本地训练后，中心服务器从客户端获取本地模型的权值及附加层参数并进行聚合处理；中心服务器利用聚合处理后的权值及附加层参数更新全局模型，并将聚合处理后的权值参数及附加层参数返回给各个客户端；各个客户端利用中心服务器返回的权值以及ground truth值进行贝叶斯估计，计算loss值，并利用返回的权值参数及附加层参数更新本地模型；重复执行直至所有客户端的loss值均收敛，则完成人流统计全局模型和本地模型的训练。 - link

• A POLYHERBAL ALCOHOL FREE FORMULATION FOR ORAL CAVITY - The present invention generally relates to a herbal composition. Specifically, the present invention relates to a polyherbal alcohol free composition comprising of Glycyrrhiza glabra root extract, Ocimum sanctum leaf extract, Elettaria cardamomum fruit extract, Mentha spicata (Spearmint) oil and Tween 80 and method of preparation thereof. The polyherbal alcohol free composition of the present invention possesses excellent antimicrobial properties and useful for oral cavity. - link

• 新型冠状病毒B.1.351南非突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B.1.351南非突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.351南非突变株RBD的基因，其核苷酸序列如SEQIDNO.1或SEQIDNO.6所示。本发明通过优化野生型新型冠状病毒南非B.1.351南非突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.351南非突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B.1.351南非突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - link

• 检测新型冠状病毒中和抗体的试剂盒及其应用 - 本发明涉及生物技术领域，具体而言，提供了一种检测新型冠状病毒中和抗体的试剂盒及其应用。本发明提供的检测新型冠状病毒中和抗体试剂盒，具体包括（a）或（b）两种方案：（a）示踪物标记的RBD三聚体抗原，包被在固体支持物上的ACE2，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；（b）示踪物标记的ACE2，包被在固体支持物上的RBD三聚体抗原，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；其中，RBD三聚体抗原利用二硫键将刺突蛋白的RBD与S2亚基完全交联得到。十二烷基二甲基甜菜碱会显著提高RBD三聚体抗原与新冠中和性抗体结合速度，提升阳性样本平均发光强度，缩短检测时间。 - link