Covid-19 Sentry

Contents

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

From Preprints

• Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19 -
  SARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear. We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to create in vitro lung models of COVID-19. Infected ALO-monolayers best recapitulated the transcriptomic signatures in diverse cohorts of COVID-19 patient-derived respiratory samples. The airway (proximal) cells were critical for sustained viral infection whereas distal alveolar differentiation (AT2[->]AT1) was critical for mounting the overzealous host immune response in fatal disease; ALO monolayers with well-mixed proximodistal airway components recapitulated both. Findings validate a human lung model of COVID-19 which can be immediately utilized to investigate COVID-19 pathogenesis, and vet new therapies and vaccines.
  🖺 Full Text HTML: Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19
• Dynamic tracking of variant frequencies depicts the evolution of mutation sites amongst SARS-CoV-2 genomes from India -
  With the exponential spread of the COVID-19 pandemic across the world within the twelve months, SARS-CoV-2 strains are continuously trying to adapt themselves in the host environment by random mutations. While doing so, some variants with evolutionary advantages such as better human to human transmissibility potential might get naturally selected. This short communication demonstrates how the mutation frequency patterns are evolving in 2,457 SAR-CoV-2 strains isolated from COVID-19 patients across diverse Indian states. We have identified 19 such variants showing contrasting mutational probabilities in the span of seven months. Out of these, 14 variants are showing increasing mutational probabilities suggesting their propagation with time due to their unexplored evolutionary advantages. Whereas mutational probabilities of five variants have significantly decreased in June onwards as compared to March/April, suggesting their termination with time. Further in-depth investigation of these identified variants will provide valuable knowledge about the evolution, infection strategies, transmission rates, and epidemiology of SARS-CoV-2.
  🖺 Full Text HTML: Dynamic tracking of variant frequencies depicts the evolution of mutation sites amongst SARS-CoV-2 genomes from India
• The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2 -
  COVID-19 can lead to acute respiratory syndrome in patients, which can be due to dysregulated immune signaling. We analyze the distribution of CpG dinucleotides, a pathogen-associated molecular pattern, in the SARS-CoV-2 genome. We find that CpG relative abundance, which we characterize by an adequate force parameter taking into account statistical constraints acting on the genome at the nucleotidic and amino-acid levels is, on the overall, low compared to other pathogenic betacoronaviruses. However, the CpG force widely fluctuates along the genome, with particularly low value, comparable to the circulating seasonal HKU1, in the Spike protein (S) coding region and high value, comparable to SARS and MERS, in the highly expressed nucleocapside (N) coding regions, whose transcripts are relatively abundant in the cytoplasm of infected cells and present in the 3'UTRs of all subgenomic RNA. This dual nature of CpG content could confer to SARS-CoV-2 the ability to avoid triggering pattern recognition receptors upon entry, while eliciting a stronger response during replication. We then investigate the evolution of synonymous mutations since the outbreak of the COVID-19 pandemic. Using a model of the viral gene evolution under human host pressure, we find that synonymous mutations seem driven, in the N protein coding region, both by the viral codon bias and by the high value of the CpG content, leading to a loss in CpG. Sequence motifs preceding these CpG-loss-associated loci match recently identified binding patterns of the Zinc finger Anti-viral Protein.
  🖺 Full Text HTML: The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2
• De novo 3D models of SARS-CoV-2 RNA elements and small- molecule-binding RNAs to aid drug discovery -
  The rapid spread of COVID-19 is motivating development of antivirals targeting conserved SARS-CoV-2 molecular machinery. The SARS-CoV-2 genome includes conserved RNA elements that offer potential small-molecule drug targets, but most of their 3D structures have not been experimentally characterized. Here, we provide a compilation of chemical mapping data from our and other labs, secondary structure models, and 3D model ensembles based on Rosetta's FARFAR2 algorithm for SARS-CoV-2 RNA regions including the individual stems in the extended 5'UTR SL1-8; the reverse complement of the 5'UTR SL1-4; the frameshift stimulating element (FSE); and the extended pseudoknot, hypervariable region, and s2m of the 3'UTR. For eleven of these elements (the stems in SL1-8, reverse complement of SL1-4, FSE, s2m, and 3'UTR pseudoknot), modeling convergence supports the accuracy of predicted low energy states; subsequent cryo-EM characterization of the FSE confirms modeling accuracy. To aid efforts to discover small molecule RNA binders guided by computational models, we provide a second set of similarly prepared models for RNA riboswitches that bind small molecules. Both datasets ('FARFAR2-SARS-CoV-2', https://github.com/DasLab/FARFAR2-SARS-CoV-2; and 'FARFAR2-Apo-Riboswitch', at https://github.com/DasLab/FARFAR2-Apo-Riboswitch) include up to 400 models for each RNA element, which may facilitate drug discovery approaches targeting dynamic ensembles of RNA molecules.
  🖺 Full Text HTML: De novo 3D models of SARS-CoV-2 RNA elements and small- molecule-binding RNAs to aid drug discovery
• Immunological memory to SARS-CoV-2 assessed for up to eight months after infection -
  Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at > 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
  🖺 Full Text HTML: Immunological memory to SARS-CoV-2 assessed for up to eight months after infection
• Mechanistic theory predicts the effects of temperature and humidity on inactivation of SARS-CoV-2 and other enveloped viruses -
  Environmental conditions affect virus inactivation rate and transmission potential. Understanding those effects is critical for anticipating and mitigating epidemic spread. Ambient temperature and humidity strongly affect the inactivation rate of enveloped viruses, but a mechanistic, quantitative theory of those effects has been elusive. We measure the stability of the enveloped respiratory virus SARS-CoV-2 on an inert surface at nine temperature and humidity conditions and develop a mechanistic model to explain and predict how temperature and humidity alter virus inactivation. We find SARS-CoV-2 survives longest at low temperatures and extreme relative humidities; median estimated virus half-life is over 24 hours at 10 {degrees}C and 40 % RH, but approximately 1.5 hours at 27 {degrees}C and 65 % RH. Our mechanistic model uses simple chemistry to explain the increase in virus inactivation rate with increased temperature and the U-shaped dependence of inactivation rate on relative humidity. The model accurately predicts quantitative measurements from existing studies of five different human coronaviruses (including SARS-CoV-2), suggesting that shared mechanisms may determine environmental stability for many enveloped viruses. Our results indicate scenarios of particular transmission risk, point to pandemic mitigation strategies, and open new frontiers in the mechanistic study of virus transmission.
  🖺 Full Text HTML: Mechanistic theory predicts the effects of temperature and humidity on inactivation of SARS-CoV-2 and other enveloped viruses
• Disparate temperature-dependent virus - host dynamics for SARS-CoV-2 and SARS-CoV in the human respiratory epithelium -
  Since its emergence in December 2019, SARS-CoV-2 has spread globally and become a major public health burden. Despite its close phylogenetic relationship to SARS-CoV, SARS-CoV-2 exhibits increased human-to-human transmission dynamics, likely due to efficient early replication in the upper respiratory epithelium of infected individuals. Since different temperatures encountered in the human respiratory tract have been shown to affect the replication kinetics of several viruses, as well as host immune response dynamics, we investigated the impact of temperatures during SARS-CoV-2 and SARS-CoV infection in the human airway epithelial cell culture model. SARS-CoV-2, in contrast to SARS-CoV, replicated more efficiently at temperatures encountered in the upper respiratory tract, and displayed higher sensitivity to type I and type III IFNs. Time-resolved transcriptome analysis highlighted a temperature-dependent and virus-specific induction of the IFN-mediated antiviral response. These data reflect clinical features of SARS-CoV-2 and SARS-CoV, as well as their associated transmission efficiencies, and provide crucial insight on pivotal virus - host interaction dynamics.
  🖺 Full Text HTML: Disparate temperature-dependent virus - host dynamics for SARS-CoV-2 and SARS-CoV in the human respiratory epithelium
• Targeted proteomics as a tool to detect SARS-CoV-2 proteins in clinical specimens. -
  The rapid, sensitive and specific detection of SARS-CoV-2 is critical in responding to the current COVID-19 outbreak. Here, we explore the potential of targeted mass spectrometry based proteomics for the detection of SARS-CoV-2 proteins in both research and clinical samples. First, we assessed the limit of detection for several SARS-CoV-2 proteins by parallel reaction monitoring (PRM) mass spectrometry. For Nucleocapsid the limit of detection was found to be in the mid-attomole range (0.9E-12 g). Next, we apply this PRM assay to the detection of viral proteins in in vitro mucus substitutes, as well as in various clinical specimens such as nasopharyngeal swabs and sputum. In this proof-of-concept study SARS-CoV-2 proteins could unambiguously be detected in clinical samples, suggesting that the sensitivity of this technology may be sufficiently high to further explore its potential role in diagnostics.
  🖺 Full Text HTML: Targeted proteomics as a tool to detect SARS-CoV-2 proteins in clinical specimens.
• Fearing the Disease or the Vaccine: The Case of COVID-19 -
  Objective: As COVID-19 continues to spread, researchers are working to develop a safe and effective vaccine. The success of an approved vaccine in stopping or slowing the pandemic will ultimately depend on the public’s acceptance of it. As studies indicate that people perceive COVID-19 as a threatening disease, the demand for a vaccine could be expected to be high. However, vaccine safety concerns might still outweigh the perceived disease risks in a decision to vaccinate against COVID-19. In the present paper, the role of perceived risk of COVID-19 (i.e., perceived likelihood of infection, perceived disease severity, and disease-related worry) and trust in the safety of a prospective vaccine against COVID-19 in predicting intentions to accept a COVID-19 vaccine was investigated. Methods: Three Finnish samples were surveyed: 856 parents of small children, 205 individuals living in an area with suboptimal vaccination coverage, and 1,325 Facebook users nationwide. As points of reference, we compared the perceptions of COVID-19 to those of influenza and measles. Results: COVID-19 was perceived as a threatening disease—more so than influenza and measles. The strongest predictor of COVID-19 vaccination intentions was trusting the safety of the potential vaccine. Those perceiving COVID-19 as a severe disease were also slightly more intent on taking a COVID-19 vaccine. Conclusions: If a vaccine against COVID-19 is successfully developed, assuring the public that the vaccine is safe should be the focus for health authorities aiming to achieve a high vaccine uptake.
  🖺 Full Text HTML: Fearing the Disease or the Vaccine: The Case of COVID-19
• Airway antibodies wane rapidly after COVID-19 but B cell memory is generated across disease severity -

  Understanding immune responses following SARS-CoV-2 infection in relation to COVID-19 severity is critical for predicting the effects of long-term immunological memory on viral spread. Here we longitudinally assessed systemic and airway immune responses against SARS-CoV-2 in a well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity; from asymptomatic infection to fatal disease. High systemic and airway antibody responses were elicited in patients with moderate to severe disease, and while systemic IgG levels were maintained after acute disease, airway IgG and IgA declined significantly. In contrast, individuals with mild symptoms showed significantly lower antibody responses but their levels of antigen-specific memory B cells were comparable with those observed in patients with moderate to severe disease. This suggests that antibodies in the airways may not be maintained at levels that prevent local virus entry upon re-exposure and therefore protection via activation of the memory B cell pool is critical.

  🖺 Full Text HTML: Airway antibodies wane rapidly after COVID-19 but B cell memory is generated across disease severity
• A model of endemic coronavirus infections -

  This work proposes that epidemiological features of both endemic coronaviruses and the recent highly pathogenic outbreak coronaviruses can be combined within an integrated framework. In this framework, mortality amongst those infected for the first time is mostly amongst the old but survivors acquire fatal infection immunity (FII). Subjects with FII can subsequently be infected and infect others without suffering significant mortality. Under these conditions, coronaviruses induce endemic infections that elicit FII in individuals during childhood when the risk of mortality is low and maintain it throughout their lifetime, thereby protecting the population against the worst effects of infection. A multi-compartment ODE model was constructed to explore the implications of this proposal on the evolution of a zoonosis sharing properties of both SARS-CoV-2 and endemic coronaviruses. The results show that mortality has two components, the first incurred during transition to endemicity and the other is exacted on a continuing basis. The relative contribution of each depends on the longevity of the FII state. In particular, a one-time vaccination of the older subpopulation is sufficient to reduce total mortality if FII is long-lived. The effect of a regular vaccination was also examined when FII was shorter lived. Herd immunity was not achieved. The validity of this proposal with regard to Covid-19 depends on whether reinfection with SARS-CoV-2 behaves in the manner expected of FII. If it does, then certain considerations apply to how Covid-19 is to be managed and how vaccine choice could influence that.

  🖺 Full Text HTML: A model of endemic coronavirus infections
• Nowhere to go: Parents' descriptions of children's physical activity during a global pandemic -
  Objective: The purpose of the study was to understand, from the perspective of parents, how the COVID-19 shelter-in-place mandates affected children’s physical activity. Design: Open-ended survey Setting: Online Method: Data were collected from 335 parents living in the United States of America. Parents answered an open-ended prompt to describe their children's physical activity during COVID-19 shelter-in-place mandates. Following data collection, inductive and deductive content analysis examined patterns in the data. Results: Analyses indicated that shelter-in-place mandates restricted children’s opportunities for physical activity. However, if families had access to outdoor spaces or equipment, they could encourage and support more physical activity opportunities than those without. Families in the lower-income bracket had less access to outdoor space and subsequently those children had fewer opportunities to be physically active. Parents supported their children’s physical activity through their involvement and encouragement. Conclusion: These findings underscore the importance of access to outdoor spaces and equipment for increasing children’s physical activity. Findings can be used by educators and policy makers to equitably support families of lower socioeconomic status who reported less access to outdoor spaces.
  🖺 Full Text HTML: Nowhere to go: Parents' descriptions of children's physical activity during a global pandemic
• Changes in work culture and workplace due to COVID19 crisis -
  Across the world when the deadly COVID-19 virus started spreading, severe health issues and death rates increased amongst thousands of people in a noticeably short period. The one and the only way to stop the transmission of the virus was to stop economic and social activities in the affected countries for an indefinite time. This research covers three main sections which are growing variations in work practices that have remained essential to stop the spread, including compulsory working from home, psychological and financial impacts that are noticeable in the aftermath of COVID-19, which includes idleness, mental illness, and dependence. Besides, the potential moderating factor of age is also examined. This research intends to deliver a consolidative methodology for studying the consequences of COVID-19 on work cultures and workplaces along with pinpointing issues for further work and understandings to advise solutions.
  🖺 Full Text HTML: Changes in work culture and workplace due to COVID19 crisis
• Molecular diversity analysis of the spike glycoprotein (S) gene from Hong Kong - China -
  In this work, 37 haplotypes of spike glycoprotein of SARS-CoV-2 from Hong Kong, China, were used. All sequences were publicly available on the Platform of the National Center for Biotechnology Information (NCBI) and were analyzed for their Molecular Variance (AMOVA), haplotypic diversity, mismatch, demographic and spatial expansion, molecular diversity and time of evolutionary divergence. The results suggested that there was a low diversity among haplotypes, with very low numbers of transitions, transversions, indels-type mutations and with total absence of population expansion perceived in the neutrality tests. The estimators used in this study supported the uniformity among all the results found and confirm the evolutionary conservation of the gene, as well as its protein product, a fact that stimulates the use of therapies based on neutralizing antibodies, such as vaccines based on protein S.
  🖺 Full Text HTML: Molecular diversity analysis of the spike glycoprotein (S) gene from Hong Kong - China
• Suppression of miR-155 attenuates lung cytokine storm induced by SARS-CoV-2 infection in human ACE2-transgenic mice -
  Coronavirus disease 2019 (COVID-19) is a recent global pandemic. It is a deadly human viral disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with a high rate of infection, morbidity and mortality. Therefore, there is a great urgency to develop new therapies to control, treat and prevent this disease. Endogenous microRNAs (miRNAs, miRs) of the viral host are key molecules in preventing viral entry and replication, and building an antiviral cellular defense. Here, we have analyzed the role of miR-155, one of the most powerful drivers of host antiviral responses including immune and inflammatory responses, in the pathogenicity of SARS-CoV-2 infection. Subsequently, we have analyzed the potency of anti-miR-155 therapy in a COVID-19 mouse model (mice transgenic for human angiotensin I- converting enzyme 2 receptor (tg-mice hACE2)). We report for the first time that miR-155 expression is elevated in COVID-19 patients. Further, our data indicate that the viral load as well as miR-155 levels are higher in male relative to female patients. Moreover, we find that the delivery of anti-miR-155 to SARS-CoV-2-infected tg-mice hACE2 effectively suppresses miR-155 expression, and leads to improved survival and clinical scores. Importantly, anti-miR-155-treated tg-mice hACE2 infected with SARS-CoV-2 not only exhibit reduced levels of pro-inflammatory cytokines, but also have increased anti-viral and anti-inflammatory cytokine responses in the lungs. Thus, our study suggests anti-miR-155 as a novel therapy for mitigating the lung cytokine storm induced by SARS-CoV-2 infection.
  🖺 Full Text HTML: Suppression of miR-155 attenuates lung cytokine storm induced by SARS-CoV-2 infection in human ACE2-transgenic mice

From Clinical Trials

• Phase II / III Study of COVID-19 DNA Vaccine (AG0302-COVID19) - Condition:   COVID-19
  Interventions:   Biological: Group A (AG0302-COVID19);   Biological: Group A (Placebo);   Biological: Group B (AG0302-COVID19);   Biological: Group B (Placebo)
  Sponsors:   AnGes, Inc.;   Japan Agency for Medical Research and Development
  Recruiting

• Changes in Viral Load in COVID-19 After Probiotics - Condition:   COVID-19
  Intervention:   Dietary Supplement: Dietary supplementation in patients with covid disease admitted to hospital
  Sponsors:   Hospital de Sagunto;   Biopolis S.L.;   Laboratorios Heel España
  Recruiting

• Efficacy and Safety of High-dose Vitamin C Combined With Chinese Medicine Against Coronavirus Pneumonia (COVID-19) - Condition:   COVID-19
  Interventions:   Drug: Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C;   Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose;   Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment
  Sponsor:   Xi'an International Medical Center Hospital
  Active, not recruiting

• Study on Safety and Clinical Efficacy of AZVUDINE in COVID-19 Patients (SARS-CoV-2 Infected) - Condition:   COVID-19
  Interventions:   Drug: AZVUDINE;   Drug: AZVUDINE placebo
  Sponsors:   HRH Holdngs Limited;   GALZU INSTITUTE OF RESEARCH, TEACHING, SCIENCE AND APPLIED TECHNOLOGY, Brazil;   SANTA CASA DE MISERICORDIA DE CAMPOS HOSPITAL (SCMCH), Brazil;   UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil
  Not yet recruiting

• Mushroom-based Product for COVID-19 - Condition:   COVID-19
  Intervention:   Drug: FoTv
  Sponsors:   Gordon Saxe;   University of California, Los Angeles;   University of California, Irvine
  Recruiting

• Study to Investigate the Treatment Effect of Colchicine in Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Colchicine;   Drug: Standard COVID-19 care
  Sponsors:   Ayub Teaching Hospital;   Universidad de Murcia
  Recruiting

• Safety and Immunogenicity Study of AdCLD-CoV19: A COVID-19 Preventive Vaccine in Healthy Volunteers - Condition:   COVID-19
  Intervention:   Biological: AdCLD-CoV19
  Sponsor:   Cellid Co., Ltd.
  Not yet recruiting

• A Controlled Phase 2/3 Study of Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Vaccine (SCB-2019) for the Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: AS03-adjuvanted SCB-2019 vaccine;   Biological: Placebo; 0.9% saline
  Sponsors:   Clover Biopharmaceuticals AUS Pty Ltd;   The Coalition for Epidemic Preparedness Innovations;   International Vaccine Institute
  Not yet recruiting

• A Study to Assess the Virologic Efficacy of REGN10933+REGN10987 Across Different Dose Regimens in Adult Outpatients With SARS-CoV-2 Infection - Condition:   COVID-19
  Interventions:   Drug: REGN10933+REGN10987 combination therapy;   Drug: Placebo
  Sponsor:   Regeneron Pharmaceuticals
  Not yet recruiting

• The Efficacy, Safety and Immunogenicity Study of Inactivated SARS-CoV-2 Vaccine for Preventing Against COVID-19 - Condition:   COVID-19
  Interventions:   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell);   Biological: Placebo
  Sponsor:   Chinese Academy of Medical Sciences
  Not yet recruiting

• Sarilumab Treatment In cytoKinE Storm Caused by Infection With COVID-19 - Condition:   COVID-19 Drug Treatment
  Intervention:   Drug: Sarilumab
  Sponsors:   Clinica Universidad de Navarra, Universidad de Navarra;   Sanofi;   Hospital Universitario Infanta Leonor
  Recruiting

• Evaluating Safety, Pharmacokinetics and Clinical Benefit of Silmitasertib (CX-4945) in Subjects With Moderate COVID-19 - Condition:   Covid19
  Interventions:   Drug: Silmitasertib;   Drug: SOC
  Sponsor:   Chris Recknor, MD
  Recruiting

• Evaluation of the Efficacy of High Doses of Methylprednisolone in SARS-CoV2 ( COVID-19) Pneumonia Patients - Condition:   Covid19
  Intervention:   Drug: Methylprednisolone, Placebo
  Sponsor:   Azienda Unità Sanitaria Locale Reggio Emilia
  Not yet recruiting

• Risk of Infection of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), COVID-19, in a Massive Musical Show With Transmission Prevention Measures - Condition:   COVID-19 (SARS-CoV-2)
  Intervention:   Behavioral: Participate in a massive musical event
  Sponsors:   Fundacio Lluita Contra la SIDA;   Dr. Bonaventura Clotet Sala;   Dr. Josep Mª LLibre Codina;   Dr. Boris Revollo Barriga;   Dra. Lidia Ruiz Tabuenca;   Dr. Ignacio Blanco Guillermo;   Dra. Andrea Alemany Ortiz;   Dr. Roger Paredes Deiros
  Recruiting

• Use of BCG Vaccine as a Preventive Measure for COVID-19 in Health Care Workers - Condition:   COVID 19 Vaccine
  Intervention:   Biological: BCG vaccine
  Sponsors:   Universidade Federal do Rio de Janeiro;   Ministry of Science and Technology, Brazil
  Recruiting

From PubMed

• Statins and PCSK9 inhibitors: What is their role in coronavirus disease 2019? - Statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors interfere with several pathophysiological pathways of coronavirus disease 2019 (COVID-19). Statins may have a direct antiviral effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by inhibiting its main protease. Statin-induced up-regulation of angiotensin-converting enzyme 2 (ACE2) may also be beneficial, whereas cholesterol reduction might significantly suppress SARS-CoV-2 by either blocking its...

• Thalidomide Combined with Short-term Low-Dose Glucocorticoid Therapy for the Treatment of Severe COVID-19: A Case-Series Study - CONCLUSIONS: Thalidomide plus short-term glucocorticoid therapy is an effective and safe regimen for the treatment of severely ill COVID-19 patients. The mechanism of action is most likely inhibition of inflammatory cytokine production.

• Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses - The Coronaviridae are a family of viruses that cause disease in humans ranging from mild respiratory infection to potentially lethal acute respiratory distress syndrome. Finding host factors common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted genome-wide CRISPR screens in cells infected by SARS-CoV-2 as well as two seasonally circulating common cold coronaviruses, OC43 and 229E. This approach...

• Understanding Views of Patients on Biologics for Psoriasis Amid the COVID-19 Pandemic - Biologics target and inhibit specific cytokines, thereby suppressing the immune system and manifestation of psoriasis. Currently, there exist limited data on the impact of biologics on the coronavirus disease of 2019 (C19). The public may obtain information from many sources which may affect their understanding of biologic use during this pandemic. This study assessed psoriasis patients' understanding of the safety of biologic use during the C19 pandemic and their perception of various...

• Diverse Functional Autoantibodies in Patients with COVID-19 - COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses ^(1-8) . While pathological innate immune activation is well documented in severe disease ¹ , the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare...

• SARS-CoV-2 Nsp16 activation mechanism and a cryptic pocket with pan-coronavirus antiviral potential - Coronaviruses have caused multiple epidemics in the past two decades, in addition to the current COVID-19 pandemic that is severely damaging global health and the economy. Coronaviruses employ between twenty and thirty proteins to carry out their viral replication cycle including infection, immune evasion, and replication. Among these, nonstructural protein 16 (Nsp16), a 2'-O-methyltransferase, plays an essential role in immune evasion. Nsp16 achieves this by mimicking its human homolog, CMTr1,...

• Binding of SARS-CoV-2 spike protein to ACE2 is disabled by thiol-based drugs; evidence from in vitro SARS-CoV-2 infection studies - Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the SARS-CoV-2 spike protein is an envelope glycoprotein that binds angiotensin converting enzyme 2 as an entry receptor. The capacity of enveloped viruses to infect host cells depends on a precise thiol/disulfide balance in their surface glycoprotein complexes. To determine if cystines in the SARS-CoV-2 spike protein maintain a native binding interface that can be disrupted by...

• Paradoxical effects of cigarette smoke and COPD on SARS-CoV2 infection and disease - CONCLUSIONS: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from uninfected COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-treatment did not affect ACE2 levels but potently inhibited SARS-CoV-2 replication in this in vitro model. These findings urge to further investigate the controversial effects of CS and COPD on SARS-CoV2 infection.

• Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19 - There is urgent therapeutic need for COVID-19, a disease for which there are currently no widely effective approved treatments and the emergency use authorized drugs do not result in significant and widespread patient improvement. The food and drug administration-approved drug ivermectin has long been shown to be both antihelmintic agent and a potent inhibitor of viruses such as Yellow Fever Virus. In this study, we highlight the potential of ivermectin packaged in an orally administrable...

• Ebselen, Disulfiram, Carmofur, PX-12, Tideglusib, and Shikonin Are Nonspecific Promiscuous SARS-CoV-2 Main Protease Inhibitors - Among the drug targets being investigated for SARS-CoV-2, the viral main protease (M^(pro)) is one of the most extensively studied. M^(pro) is a cysteine protease that hydrolyzes the viral polyprotein at more than 11 sites. It is highly conserved and has a unique substrate preference for glutamine in the P1 position. Therefore, M^(pro) inhibitors are expected to have broad-spectrum antiviral activity and a high selectivity index. Structurally diverse compounds have been reported as M^(pro)...

• Development of a High-Throughput Homogeneous AlphaLISA Drug Screening Assay for the Detection of SARS-CoV-2 Nucleocapsid - The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is in urgent need of therapeutic options. High-throughput screening (HTS) offers an opportunity to rapidly identify such compounds. In this work, we have developed a homogeneous cell-based HTS system using AlphaLISA detection technology for the SARS-CoV-2 nucleocapsid protein (NP). Our assay measures both recombinant and endogenous NP from viral lysates and tissue culture...

• Probing the Dynamic Structure-Function and Structure-Free Energy Relationships of the Coronavirus Main Protease with Biodynamics Theory - The SARS-CoV-2 main protease (M^(pro)) is of major interest as an antiviral drug target. Structure-based virtual screening efforts, fueled by a growing list of apo and inhibitor-bound SARS-CoV/CoV-2 M^(pro) crystal structures, are underway in many laboratories. However, little is known about the dynamic enzyme mechanism, which is needed to inform both assay development and structure-based inhibitor design. Here, we apply biodynamics theory to characterize the structural dynamics of...

• Shaping the post-COVID-19 "New Normal" with Communication and Collaboration Platforms: state of the art communications for radiology, oncology, MDTs and beyond - The COVID-19 pandemic has driven the use of digital communications to unprecedented levels across society whilst the NHS struggles with non-compatible IT systems that are often outdated and inhibit effective communication. MDTs use teleconferencing but the IT infrastructure does not permit clinicians to readily discuss cases and collaboratively review imaging outside of formal meetings if not on the same site and face-to-face. NHS radiology home reporting was not widely in place at the outbreak...

• Acute Effects of an Afterschool Running and Reading Program on Executive Functioning in Children: An Exploratory Study - Objective: Emerging research within school settings suggests acute forms of physical activity and exercise lead to improvements in executive functioning among children. However, research pertaining to these effects within the afterschool setting remains limited. The primary purpose of this study was to investigate the acute effects of a community-based afterschool running and reading program on executive functioning in 8 to 12-year-old children. Method: Fifty participants were initially...

• Docking Characterization and in vitro Inhibitory Activity of Flavan-3-ols and Dimeric Proanthocyanidins Against the Main Protease Activity of SARS-Cov-2 - We report to use the main protease (M^(pro)) of SARS-Cov-2 to screen plant flavan-3-ols and proanthocyanidins. Twelve compounds, (-)-afzelechin (AF), (-)-epiafzelechin (EAF), (+)-catechin (CA), (-)-epicatechin (EC), (+)-gallocatechin (GC), (-)-epigallocatechin (EGC), (+)-catechin-3-O-gallate (CAG), (-)-epicatechin-3-O-gallate (ECG), (-)-gallocatechin-3-O-gallate (GCG), (-)-epigallocatechin-3-O-gallate (EGCG), procyanidin A2 (PA2), and procyanidin B2 (PB2), were selected for docking simulation....

From Patent Search

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

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

• 疫苗融合蛋白 - 本申请涉及一种融合蛋白，所述融合蛋白包括SARS‑CoV‑2抗原多肽和鞭毛蛋白或其片段。本申请还提供了所述融合蛋白的制备方法和用途。本申请所述的融合蛋白能够诱导机体产生针对SARS‑CoV类病毒的抗原的细胞免疫反应。

• AN EFFICIENT METHODOLOGY TO MANAGE THE ADMISSIONS IN HOSPITALS DURING THE PANDEMICS SUCH AS COVID 19 -

• 一种SARS-CoV-2假病毒小鼠体内包装系统及其制备方法 - 本发明提供了一种假病毒小鼠体内包装系统的制备方法，包括以下步骤：S1基于慢病毒包装质粒系统和睡美人转座子系统构建SARS‑CoV‑2假病毒包装质粒系统，S2将步骤S1中SARS‑CoV‑2假病毒包装质粒系统与睡美人转座酶表达质粒混合通过水动力注射的方式转染小鼠肝细胞，然后睡美人转座子系统将SARS‑CoV‑2假病毒包装所需序列以剪切粘贴的方式整合到小鼠肝细胞的基因组。本发明可在小鼠体内持续制造分泌SARS‑CoV‑2假病毒，可模拟靶器官被SARS‑CoV‑2病毒持续侵入攻击的过程，从而可模拟出新冠肺炎（COVID‑19）的病理特征。基于SARS‑CoV‑2假病毒小鼠体内包装系统的动物模型安全性高，不需要P3级实验室就能开展研究。利用水动力注射的方式引入SARS‑CoV‑2假病毒包装质粒系统操作简单，成本低。

• 柴胡解毒药物组合物及其制备方法和应用 - 本发明属于中药领域，具体涉及一种柴胡解毒药物组合物及其制备方法和应用，所述柴胡解毒药物组合物以质量份计由如下原料组分制成：柴胡30_{60份，黄芩15}30份，法半夏15_{30份，生姜15}30份，大枣5_{10份，枳实20}40份，大黄10_{20份，桃仁10}20份，白芍15~30份。本发明的柴胡解毒药物组合物能够显著改善普通型COVID‑19引起的咳嗽；能改善疫毒闭肺型重型COVID‑19引起的咳嗽，显著改善疫毒闭肺型重型COVID‑19引起的胸闷、气短和乏力等主要症状。另外经大量临床观察，本发明的柴胡解毒药物组合物能够显著改善疫毒闭肺型重型COVID‑19引起的发热面红，咳嗽，痰黄粘少，或痰中带血，喘憋气促，疲乏倦怠，口干苦粘，大便不畅，小便短赤等症状。

• 一种新型冠状病毒RBD核苷酸序列、优化方法与应用 - 本发明公开了一种新型冠状病毒RBD核苷酸序列、优化方法与应用。属于基因工程技术领域。优化步骤：（1）对野生型新型冠状病毒RBD核苷酸序列进行初步优化；（2）将宿主细胞特异性高表达分泌蛋白信号肽序列进行优化；（3）将人IgG1‑Fc核苷酸序列进行优化；（4）将步骤（2）优化后的宿主细胞特异性高表达分泌蛋白信号肽核苷酸序列、步骤（1）得到的初步优化新型冠状病毒RBD核苷酸序列、连接子核苷酸序列和步骤（3）优化后的人IgG1‑Fc核苷酸序列依次连接即可。与现有技术相比，本发明的有益效果：产生的克隆表达效率比野生新型冠状病毒RBD序列提高了约12倍，比中国仓鼠密码子偏性优化序列克隆表达效率提高了2倍。

• ASSISTING COMPLEX FOR TAKING OF BIOMATERIAL FROM MOUTH IN PANDEMIC CONDITIONS - FIELD: medicine. SUBSTANCE: invention refers to medicine, namely to methods for contactless taking of biomaterial in tested person. Taking the biomaterial in the tested person is carried out in a room located in a dirty zone and separated by a partition from the clean zone, in which there is a laboratory assistant performing the procedure using a robotic complex. Complex includes digital controller, manipulator with tool unit, small manipulator, camera, monitor, control system of digital controller, manipulator, small manipulator, and complex control system. In the partition there are two holes: one – for installation and passage of the swab, the other – for the test tube installation. In the dirty zone there is a small manipulator having two actuators: one for movement of a test tube with a swab, and the second for positioning and placing a disposable mouthpiece. EFFECT: reduced risk of laboratory assistant and tested person infection by avoiding their direct contact. 17 cl, 1 dwg

• Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19 -

  Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.

• Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19 -

  Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.