Covid-19 Sentry

Contents

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

From Preprints

• Association between COVID-19, mobility and environment in São Paulo, Brazil -

  Brazil, the country most impacted by the coronavirus disease 2019 (COVID-19) on the southern hemisphere, use intensive care admissions per day, mobility and other indices to monitor quarantines and prevent the transmissions of SARS-CoV-2. In this study we quantified the associations between residential mobility index (RMI), air pollution, meteorology, and daily cases and deaths of COVID-19 in Sao Paulo, Brazil. We applied a semiparametric generalized additive model (GAM) to estimate: 1) the association between RMI and COVID-19, accounting for ambient particulate matter (PM2.5), ozone (O3), relative humidity, temperature and delayed exposure between 3-21 days, and 2) the association between COVID-19 and exposure to for ambient particulate matter (PM2.5), ozone (O3), accounting for relative humidity, temperature and mobility. We found that an RMI of 45.28% results in 1,212 cases (95% CI: 1,189 to 1,235) and 44 deaths (95% CI: 40 to 47). Increasing the isolation from 45.28% to 50% would avoid 438 cases and 21 deaths. Also, we found that an increment of 10 μgm-3 of PM2.5 results in a risk of 1.140 (95% CI: 1.021 to 1.274) for cases and 1.086 (95% CI: 1.008 to 1.170) for deaths, while O3 produces a relative risk of 1.075 (95% CI: 1.006 to 1.150) for cases and 1.063 (95% CI: 1.006 to 1.124) for deaths, respectively. We compared our results with observations and literature review, finding well agreement. Policymakers can use such mobility indices as tools to control social distance activities. Spatial distancing is an important factor to control COVID-19. Small increments of air pollution result in an increased number of COVID-19 cases and deaths.

  🖺 Full Text HTML: Association between COVID-19, mobility and environment in São Paulo, Brazil
• SARS-CoV-2 Alpha, Beta and Delta variants display enhanced Spike-mediated Syncytia Formation -
  Severe COVID-19 is characterized by lung abnormalities, including the presence of syncytial pneumocytes. Syncytia form when SARS-CoV-2 spike protein expressed on the surface of infected cells interacts with the ACE2 receptor on neighbouring cells. The syncytia forming potential of spike variant proteins remain poorly characterized. Here, we first assessed Alpha and Beta spread and fusion in cell cultures. Alpha and Beta replicated similarly to D614G reference strain in Vero, Caco-2, Calu-3 and primary airway cells. However, Alpha and Beta formed larger and more numerous syncytia. Alpha, Beta and D614G fusion was similarly inhibited by interferon induced transmembrane proteins (IFITMs). Individual mutations present in Alpha and Beta spikes differentially modified fusogenicity, binding to ACE2 and recognition by monoclonal antibodies. We further show that Delta spike also triggers faster fusion relative to D614G. Thus, SARS-CoV-2 emerging variants display enhanced syncytia formation.
  🖺 Full Text HTML: SARS-CoV-2 Alpha, Beta and Delta variants display enhanced Spike-mediated Syncytia Formation
• Regional Variant Analysis of Spike Glycoprotein Mutations of SARS-CoV-2 and Its Implications in COVID-19 Pandemic Control -
  Mutations in the spike glycoprotein have various impacts on the receptor binding, antibody in-teraction, and host range of SARS-CoV-2. As the interaction of spike glycoprotein with the human ACE2 receptor is the entry point of SARS- CoV-2 in human cells, mutations in the spike protein it-self contain numerous impacts on the pandemic. Here, we analysed all the mutations in the spike glycoprotein from123 strains isolated from Kerala, India. We also predicted the possible struc-tural relevance of the unique mutations based on topological analysis of the residue interaction network of the spike glycoprotein structure.
  🖺 Full Text HTML: Regional Variant Analysis of Spike Glycoprotein Mutations of SARS-CoV-2 and Its Implications in COVID-19 Pandemic Control
• Allosteric perspective on the mutability and druggability of the SARS-CoV-2 Spike protein -
  Recent developments in the SARS-CoV-2 pandemic point to its inevitable transformation into an endemic disease, urging both diagnostics of emerging variants of concern (VOCs) and design of the variant-specific drugs in addition to vaccine adjustments. Exploring the structure and dynamics of the SARS-CoV-2 Spike protein, we argue that the high mutability characteristic of RNA viruses coupled with the remarkable flexibility and dynamics of viral proteins result in a substantial involvement of allosteric mechanisms. While allosteric effects of mutations should be considered in predictions and diagnostics of new VOCs, allosteric drugs advantageously avoid escaping mutations via non-competitive inhibition originating from many alternative distal locations. The exhaustive allosteric signalling and probing maps provide a comprehensive picture of allostery in the Spike protein, making it possible to locate sites of potential mutations that could work as new VOCs ‘drivers’, and to determine binding patches that may be targeted by newly developed allosteric drugs.
  🖺 Full Text HTML: Allosteric perspective on the mutability and druggability of the SARS-CoV-2 Spike protein
• Analysis of B-cell receptor repertoires in COVID-19 patients using deep embedded representations of protein sequences -
  Analyzing B-cell receptor (BCR) repertoires is immensely useful in evaluating one’s immunological status. Conventionally,repertoire analysis methods have focused on comprehensive assessment of clonal compositions, including V(D)J segment usage, nucleotide insertion/deletion, and amino acid distribution. Here, we introduce a novel computational approach that applies deep-learning based protein embedding techniques to analyze BCR repertoires. By selecting the most frequently occurring BCR sequences in a given repertoire and computing the sum of the vector representations of these sequences, we represent an entire repertoire as a 100-dimensional vector and eventually as a single data point in vector space. We demonstrate that our new approach enables us to not only accurately cluster repertoires of COVID-19 patients and healthy subjects, but also efficiently track minute changes in immunity conditions as patients undergo a course of treatment over time. Furthermore, using the distributed representations, we successfully trained an XGBoost classification model that achieved over 87% mean accuracy rate given a repertoire of CDR3 sequences.
  🖺 Full Text HTML: Analysis of B-cell receptor repertoires in COVID-19 patients using deep embedded representations of protein sequences
• Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 responses -
  Nucleoside modified mRNA combined with Acuitas Therapeutics’ lipid nanoparticles (LNP) have been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs’ ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper cells (Tfh) and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD- specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS- CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, the still high antibody titers were sufficient to confer protection towards lethal viral challenges. We further found that IL-6, but not neutrophils, was required to generate Tfh cells and antibody responses. In summary, here we bring evidence that the mRNA-LNP platform can support protective adaptive immune responses in the absence of specific DC subsets through an IL-6 dependent and neutrophil independent mechanism.
  🖺 Full Text HTML: Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 responses
• The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin α5β1 and NF-κB -
  Vascular endothelial cells (EC) form a critical interface between blood and tissues that maintains whole-body homeostasis. In COVID-19, disruption of the EC barrier results in edema, vascular inflammation, and coagulation, the hallmarks of the severe disease. However, the mechanisms by which EC are dysregulated in COVID-19 are unclear. Here, we show that the spike protein of SARS-CoV-2 alone activates the EC inflammatory phenotype in a manner dependent on integrin 5{beta}1 signaling. Incubation of human umbilical vein EC with whole spike, its receptor-binding domain, or the integrin-binding tripeptide RGD induced the nuclear translocation of NF-{kappa}B and enhanced the expression of leukocyte adhesion molecules VCAM1 and ICAM1, the adhesion of peripheral blood leukocytes, and the permeability of the monolayer. Inhibitors of integrin 5{beta}1 activation prevented these effects. We suggest that the spike protein, through its RGD motif in the receptor-binding domain, binds to integrin 5{beta}1 in EC to activate Rho GTPases, eNOS pathways, and the NF-{kappa}B gene expression program responsible for vascular leakage and leukocyte infiltration, respectively. These findings uncover a new direct action of SARS-CoV-2 on EC dysfunction and introduce integrin 5{beta}1 as a promising target for treating vascular inflammation in COVID-19.
  🖺 Full Text HTML: The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin α5β1 and NF-κB
• SARS-CoV-2 fears green: the chlorophyll catabolite Pheophorbide a is a potent antiviral -
  The SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances at good pace, effectiveness against emerging variants of the virus is unpredictable. The virus has displayed a remarkable resistance to treatments and no drugs have been proved fully effective against Covid-19. Thus, despite the international efforts, there is still an urgent need for new potent and safe antivirals against SARS-CoV-2. Here we exploited the enormous potential of plant metabolism, in particular the bryophyte Marchantia polymorpha, and following a bioactivity-guided fractionation and mass-spectrometry approach, identified a potent SARS-CoV-2 antiviral. We found that the chlorophyll derivative Pheophorbide a (PheoA), a natural porphyrin similar to animal Protoporphyrin IX, has an extraordinary antiviral activity against SARS-CoV-2 preventing infection of cultured monkey and human cells, without noticeable citotoxicity. We also show that PheoA prevents coronavirus entry into the cells by directly targeting the viral particle. Besides SARS-CoV-2, PheoA also displayed a broad-spectrum antiviral activity against (+)strand RNA viral pathogens such as HCV, West Nile, and other coronaviruses, but not against (-)strand RNA viruses, such as VSV. Our results indicate that PheoA displays a remarkable potency and a satisfactory therapeutic index, and suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2. Moreover, PheoA adds to remdesivir’s efficiency and is currently employed in photoactivable cancer therapies in humans.
  🖺 Full Text HTML: SARS-CoV-2 fears green: the chlorophyll catabolite Pheophorbide a is a potent antiviral
• Immune Functional Capability Dynamics Determine Disease Outcomes as in Cancer, Heart Diseases, COVID-19, Etc. -
  Having proved flaws in using clinical trials to study weak factors, we want to investigate how life factors affect health and diseases. In this study, we show that cancer, heart disease and infectious diseases are inherently preventable and curable. We would like to find how life factors revolving around environment, emotion, activity, disease agents, diets, behaviors, etc. affect disease outcomes. We expand the scope of the immune functions to include functions for removing garbage and repairing tissue damages, and then identify six classes of health properties for evaluating the immune system’s actual functional capabilities. In this model, personal ability to resist infection depends on the immune system’s current functional capabilities, and the ability to resolve existing diseases depends on the immune system’s actual functional capabilities integrated over a relevant time. We show how each life factor affects the immune system’s current functional capabilities by examining its effects on any of the six classes of properties. Many seemingly irrelevant factors can affect disease outcomes because they share biological resources for removing garbage, repairing tissue damages and maintaining all vital functions. Thus, we found that rational strategies for conquering diseases are identifying disease causes, avoiding exposure to disease agents, detoxifying toxic substances, and using seemingly-irrelevant life factors to boost real-time immune functional capabilities and vital organ functions. All chronic diseases including personal resistance to SARS-CoV-2 are influenced by N and M factors, where N represents the number of factors related to disease causes, and M represents the number of factors that influence the immune functional capacities and organ capacities. Most of N factors are pollutants while most of M factors are created social practices that are formed after industrial revolution. It is time to address toxic substances and examine health-ruining social practices in education, employment, business, litigation, promotion, etc. which is responsible for switching on human stress hormones for months and years, with predictable adverse effects on human health.
  🖺 Full Text HTML: Immune Functional Capability Dynamics Determine Disease Outcomes as in Cancer, Heart Diseases, COVID-19, Etc.
• MVsim: a toolset for quantifying and designing multivalent interactions -
  Arising through multiple binding elements, multivalency can specify the avidity, duration, cooperativity, and selectivity of biomolecular interactions, but quantitative prediction and design of these properties has remained challenging. Here we present MVsim, an application suite built around a configurational network model of multivalency to facilitate the quantification, design, and mechanistic evaluation of multivalent binding phenomena through a simple graphical user interface. To demonstrate the utility and versatility of MVsim, we first show that both monospecific and multispecific multivalent ligand-receptor interactions, with their noncanonical binding kinetics, can be accurately simulated. We then quantitatively predict the ultrasensitivity and performance of multivalent-encoded protein logic gates, evaluate the inherent programmability of multispecificity for selective receptor targeting, and extract rate constants of conformational switching for the SARS-CoV-2 spike protein and model its binding to ACE2 as well as multivalent inhibitors of this interaction. MVsim is freely available at https://sarkarlab.github.io/MVsim/.
  🖺 Full Text HTML: MVsim: a toolset for quantifying and designing multivalent interactions
• Ten rules for conducting retrospective pharmacoepidemiological analyses: example COVID-19 study -
  Since the beginning of the COVID-19 pandemic, pharmaceutical treatment hypotheses have abounded, each requiring careful evaluation. A randomized controlled trial generally provides the most credible evaluation of a treatment, but the efficiency and effectiveness of the trial depend on the existing evidence supporting the treatment. The researcher must therefore compile a body of evidence justifying the use of time and resources to further investigate a treatment hypothesis in a trial. An observational study can provide this evidence, but the lack of randomized exposure and the researcher’s inability to control treatment administration and data collection introduce significant challenges. A proper analysis of observational health care data thus requires contributions from experts in a diverse set of topics ranging from epidemiology and causal analysis to relevant medical specialties and data sources. Here we summarize these contributions as 10 rules that serve as an end-to-end introduction to retrospective pharmacoepidemiological analyses of observational health care data using a running example of a hypothetical COVID-19 study. A detailed supplement presents a practical how-to guide for following each rule. When carefully designed and properly executed, a retrospective pharmacoepidemiological analysis framed around these rules will inform the decisions of whether and how to investigate a treatment hypothesis in a randomized controlled trial. This work has important implications for any future pandemic by prescribing what we can and should do while the world waits for global vaccine distribution.
  🖺 Full Text HTML: Ten rules for conducting retrospective pharmacoepidemiological analyses: example COVID-19 study
• COVID-19 Mortality in Women and Men in Sub-Saharan Africa: A Cross Sectional Study -

  Objective: To investigate differences of COVID-19 related mortality among women and men across sub-Saharan Africa (SSA) from the beginning of the pandemic. Design: A cross sectional study. Setting: Data from 20 member nations of the WHO African region until September 1, 2020. Participants: 69,580 cases of COVID-19, stratified by sex (men, n=43071; women, n=26509) and age (0-39 years, n=41682; 40-59 years, n=20757; 60+ years, n=7141). Main outcome measures: We computed the SSA- and country-specific case fatality rates (CFRs) and sex-specific CFR differences across various age groups, using a Bayesian approach. Results: A total of 1,656 (2.4% of total cases reported; 1656/69580) deaths were reported, with men accounting for 1168/1656 (70.5%) of total deaths. In SSA, women had a lower CFR than men (mean CFR<diff> = -0.9%; 95% credible intervals -1.1% to -0.6%). The mean CFR estimates increased with age, with the sex-specific CFR differences being significant among those aged 40 or more (40-59 age- group: mean CFR<diff> = -0.7%; 95% credible intervals -1.1% to -0.2%; 60+ age-group: mean CFR<diff> = -3.9%; 95% credible intervals -5.3% to -2.4%). At the country level, seven of the twenty SSA countries reported significantly lower CFRs among women than men overall. Moreover, corresponding to the age-specific datasets, significantly lower CFRs in women than men were observed in the 60+ age-group in seven countries and 40-59 age-group in one country. Conclusions: Sex and age are important predictors of COVID-19 mortality. Countries should prioritize the collection and use of sex-disaggregated data to understand the evolution of the pandemic. This is essential to design public health interventions and ensure that policies promote a gender sensitive public health response.

• Safety and efficacy of Pulmonary physiotherapy in hospitalized patients with severe COVID-19 pneumonia (PPTCOVID Study): A prospective, randomised, single-blind, controlled trial -

  Background: Pulmonary physiotherapy (PPT) is an important treatment in the management of patients with different types of pulmonary disorders. We aimed to evaluate safety and efficacy of PPT in hospitalized patients with severe COVID-19 pneumonia. Methods: In this randomised, single-blind, controlled trial, we enrolled hospitalized, non-intubated patients (18 to 75 years with oxygen saturation (Spo2) in free-air breathing ≤90%) with COVID-19 pneumonia at a referral hospital. Participants were randomly assigned (1:1) to receive PPT (six sessions PPT with breathing exercises and airway clearance techniques) or basic care. The primary outcomes were venous blood O2 (pO2) and CO2 (pCO2) pressures, Spo2, and three-minute walking test (3MWT) that were assessed before and end of sixth session. Secondary outcomes included level of dyspnea, venous blood PH, one-month mortality, three-month mortality and short form-36 (SF-36) after one and three months. The assessor was blinded to the assignment. This trial is registered with ClinicalTrials.gov (NCT04357340). Findings: In April-May 2020, 40 participants were randomly assigned to PPT or basic care groups. While at the end of intervention, pO2 (adjusted mean difference to baseline measure (AMD) 6.43 mmHg [95%CI 2.8, 10.07], P<0.01), Spo2 (AMD 4.43% [95%CI 2.04, 6.83], P=0.0011), and 3MTW (AMD 91.44 m [95%CI 68.88, 113.99], P<0.01) were higher in PPT group and basic care group, pCO2 was not improved (AMD -2.1 mmHg [95%CI-6.36, 2.21], P=0.33). Mortality rate was 20% (OR adjusted to baseline Spo2 .19 [95%CI .03, 1.30], P=.09) and 25% (OR adjusted to baseline Spo2 .16 [95%CI .26, 1.05], P=.056) lower in the PPT group at three-month at one-month and three-month, respectively. There were no significant differences in most SF-36 domains scores after one and three months. No serious adverse event was observed during PPT sessions. Conclusion: Early PPT can be considered a safe and effective therapeutic choice for patients with severe COVID-19.

  🖺 Full Text HTML: Safety and efficacy of Pulmonary physiotherapy in hospitalized patients with severe COVID-19 pneumonia (PPTCOVID Study): A prospective, randomised, single-blind, controlled trial
• The COVID-19 pandemic in Africa’s Island Nations: A descriptive study of the course of the COVID-19 outbreaks and the national response plans -
  Introduction: The main objective is to present an overview of the evolution of the COVID-19 pandemic in the six African island nations: Cabo Verde, Comoros, Madagascar, Mauritius, São Tomé e Príncipe and Seychelles, up until 29 November 2020. The relevance of studying the outbreak in these countries is their distinct geography, which may facilitate rapid closure and control of their international borders. Here, we investigate whether this geography may have led to an effective response and management of their respective COVID-19 epidemics. Methods: A literature review and analysis of national public health reports, official coronavirus websites and previously published research in each of the studied countries from the start of the pandemic through 29 November 2020 was performed. Data on metrics on the country-specific progression of COVID-19, the level of strictness of the governmental policies, the testing practices, as well the national healthcare systems, the description and the state of health of the populations in the African island nations were reported. Results: Five out of six countries controlled their respective COVID-19 epidemics at an early stage in the context of the total number of confirmed cases and deaths. In Cabo Verde, there was an increasing number of cases as of 29 November 2020, when 10,526 total cases and 104 total deaths were reported nationally. All six nations maintained a case fatality rate (CFR) lower than the global average, estimated between 2 - 3% in previously published research. Among the island nations, Mauritius had the highest CFR of 2%. Discussion: African island nations have different demographic, socioeconomic, and healthcare profiles. However, their shared geographic characteristics likely played a role in limiting the spread of the infection. Furthermore, data from these nations support the idea that the implementation of strict restrictions at an early stage, such as border closure and lockdowns, was crucial for the epidemic response.
  🖺 Full Text HTML: The COVID-19 pandemic in Africa’s Island Nations: A descriptive study of the course of the COVID-19 outbreaks and the national response plans
• Distant Residues Modulate Conformational Opening in SARS-CoV-2 Spike Protein -
  Infection by SARS-CoV-2 involves the attachment of the receptor binding domain (RBD) of its spike proteins to the ACE2 receptors on the peripheral membrane of host cells. Binding is initiated by a down to up conformational change in the spike protein, an opening which presents the RBD to the receptor. To date, computational and experimental studies that search for therapeutics have concentrated, for good reason, on the RBD. However, the RBD region is highly prone to mutations, and is therefore a hotspot for drug resistance. In contrast, we here focus on the correlations between the RBD and residues distant to it in the spike protein. This allows for a deeper understanding of the underlying molecular recognition events and prediction of the highest-effect key mutations in distant, allosteric sites, with implications for therapeutics. Also, these sites can appear in emerging mutants with possibly higher transmissibility and virulence, and pre-identifying them can give clues for designing pan-coronavirus vaccines against future outbreaks. Our model, based on time-independent component analysis (tICA) and protein graph connectivity network, is able to identify multiple residues that exhibit long-distance coupling with the RBD opening. Residues involved in the most ubiquitous D614G mutation and the A570D mutation of the highly contagious UK SARS-CoV-2 variant are predicted ab-initio from our model. Conversely, broad spectrum therapeutics like drugs and monoclonal antibodies can target these key distant-but-conserved regions of the spike protein.
  🖺 Full Text HTML: Distant Residues Modulate Conformational Opening in SARS-CoV-2 Spike Protein

From Clinical Trials

• Phase II/III Study of AZD2816, for the Prevention of COVID-19 in Adults - Conditions:   COVID-19;   SARS-CoV-2
  Interventions:   Biological: AZD1222;   Biological: AZD2816
  Sponsor:   AstraZeneca
  Recruiting

• Clinical Trial For Early SARS-CoV-2 (COVID-19) Treatment - Condition:   Covid19
  Interventions:   Drug: Hydroxychloroquine;   Drug: Favipiravir;   Drug: Favipiravir + Hydroxychloroquine;   Drug: Placebo
  Sponsor:   Health Institutes of Turkey
  Completed

• Echinacea Drug for Covid-19 - Condition:   Covid19
  Intervention:   Drug: ECHINACEA ARKOPHARMA
  Sponsors:  
  Jesús R. Requena;   IDIS;   SALUD;   Laboratoires Arkopharma
  Recruiting

• Effects of Respiratory Muscle Training in Patients With Post COVID-19 - Condition:   Covid19
  Interventions:   Other: Exercise training group;   Other: Control training group
  Sponsor:   Gazi University
  Completed

• SOLIDARITY Finland Long COVID-19 - Condition:   Covid19
  Intervention:   Drug: Remdesivir
  Sponsors:  
  Clinical Urology and Epidemiology Working Group;   University of Helsinki;   World Health Organization;   Helsinki University Central Hospital;   Hyvinkää Hospital;   Kanta-Häme Central Hospital;   Kuopio University Hospital;   Oulu University Hospital;   Porvoo Hospital;   Seinajoki Central Hospital;   Mikkeli Central Hospital;   Tampere University Hospital
  Recruiting

• Vaccination for Recovered Inpatients With COVID-19 (VATICO) - Condition:   Covid19
  Interventions:   Biological: Moderna mRNA-1273 COVID-19 vaccine;   Biological: Pfizer BNT162b2 COVID-19 vaccine
  Sponsors:   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Minnesota;   National Institute of Allergy and Infectious Diseases (NIAID);   University of Copenhagen;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Medical Research Council
  Not yet recruiting

• COVID-19 and Lung Ultrasound Utility - Condition:   Covid19
  Intervention:   Device: Device: Butterfly iQ
  Sponsor:  
  Rocket Doctor Inc.
  Recruiting

• Efficacy of Canrenone as add-on Treatment in Moderate to Severe ARDS in COVID-19 - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Intervention:  
  Drug: Potassium Canrenoate
  Sponsors:   Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico;   University of Milan;   IRCCS Azienda Ospedaliero-Universitaria di Bologna
  Not yet recruiting

• Saliva-based COVID-19 DNA Aptamer Test - Condition:   Covid19
  Intervention:   Device: AptameX
  Sponsors:   Achiko AG;   Udayana University
  Recruiting

• Evaluation of The Efficacy of Triazavirin Versus Oseltamivir in Egyptian Patients Infected With COVID-19 - Condition:   Covid19
  Intervention:   Drug: standard treatment COVID-19 + Triazavirin
  Sponsor:   Ain Shams University
  Recruiting

• The Efficacy of Nigella Sativa Versus VitaminD3 as Supplement Therapy in Coronavirus Disease 2019 (COVID-19) - Condition:   Covid19
  Intervention:   Dietary Supplement: Nigella Sativa capsule twice daily
  Sponsor:   Ain Shams University
  Recruiting

• Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients With COVID-19 - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Cyproheptadine
  Sponsor:  
  Hospital de Clinicas de Porto Alegre
  Not yet recruiting

• Intervention to Promote COVID-19 Vaccination - Conditions:   Covid19;   Vaccination
  Intervention:   Behavioral: Health System Vaccination Text Messages
  Sponsors:   University of Massachusetts, Worcester;   National Institute on Minority Health and Health Disparities (NIMHD)
  Not yet recruiting

• Effects of COVID-19 on Cavernous Smooth Muscle - Conditions:   Erectile Dysfunction Due to Diseases Classified Elsewhere;   Covid19
  Intervention:  
  Diagnostic Test: corpus cavernosum electromyography
  Sponsor:   Ankara Yildirim Beyazıt University
  Completed

• Booster Vaccination Against SARS-CoV-2 - Condition:   Covid19
  Intervention:   Biological: CoronaVac
  Sponsor:  
  Health Institutes of Turkey
  Recruiting

From PubMed

• NICEdrug.ch, a workflow for rational drug design and systems-level analysis of drug metabolism - The discovery of a drug requires over a decade of intensive research and financial investments - and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied their enzymatic metabolic targets, fate, and toxicity. NICEdrug.ch includes a unique fingerprint that identifies reactive similarities between drug-drug and drug-metabolite pairs. We validated the application, scope, and performance of…

• The TMPRSS2 Inhibitor Nafamostat Reduces SARS-CoV-2 Pulmonary Infection in Mouse Models of COVID-19 - The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality on a global scale. The etiologic agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), initiates host cell entry when its spike protein (S) binds to its receptor, angiotensin-converting enzyme 2 (ACE2). In airway epithelia, the spike protein is cleaved by the cell surface protease TMPRSS2, facilitating membrane fusion and entry at the cell surface. This dependence on TMPRSS2 and related…

• Why All the Fury over Furin? - Analysis of the SARS-CoV-2 sequence revealed a multibasic furin cleavage site at the S1/S2 boundary of the spike protein distinguishing this virus from SARS-CoV. Furin, the best-characterized member of the mammalian proprotein convertases, is an ubiquitously expressed single pass type 1 transmembrane protein. Cleavage of SARS-CoV-2 spike protein by furin promotes viral entry into lung cells. While furin knockout is embryonically lethal, its knockout in differentiated somatic cells is not, thus…

• Potential inhibitors of the main protease of SARS-CoV-2 and modulators of arachidonic acid pathway: Non-steroidal anti-inflammatory drugs against COVID-19 - The main protease of SARS-CoV-2 is one of the key targets to develop and design antiviral drugs. There is no general agreement on the use of non-steroidal anti-inflammatory drugs (NSAIDs) in COVID-19. In this study, we investigated NSAIDs as potential inhibitors for chymotrypsin-like protease (3CLpro) and the main protease of the SARS-CoV-2 to find out the best candidates, which can act as potent inhibitors against the main protease. We also predicted the effect of NSAIDs on the arachidonic…

• Microstructured Surfaces for Reducing Chances of Fomite Transmission via Virus-Containing Respiratory Droplets - Evaporation-induced particle aggregation in drying droplets is of significant importance in the prevention of pathogen transfer due to the possibility of indirect fomite transmission of the infectious virus particles. In this study, particle aggregation was directionally controlled using contact line dynamics (pinned or slipping) and geometrical gradients on microstructured surfaces by the systematic investigation of the evaporation process on sessile droplets and sprayed microdroplets laden…

• The Development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates - Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a series of single-domain antibodies (i.e., nanobody), Nanosota-1, from a camelid nanobody phage display library. Structural data showed that Nanosota-1 bound to the oft-hidden receptor-binding domain (RBD) of SARS-CoV-2 spike protein, blocking viral receptor ACE2. The lead drug candidate possessing an Fc tag (Nanosota-1C-Fc) bound to SARS-CoV-2 RBD ~3000 times more tightly than ACE2 did and inhibited…

• Remdesivir for treatment of COVID 19; review of the pharmacological properties, safety and clinical effectiveness - INTRODUCTION: Remdesivir is a nucleoside analog, which inhibits viral RNA replication by blocking RNA-dependent RNA polymerase. First developed and tested during the Ebola epidemic, repurposed, and gained prominence during the Coronavirus disease 19 (COVID 19) pandemic. Based on data from three major trials, remdesivir became the first and only medication to obtain approval from the Food and Drug Administration (FDA) to treat patients hospitalized with COVID 19 disease.

• Serum antibody response to BNT162b2 after natural SARS-CoV-2 infection - CONCLUSIONS: Compared with naïve individuals, seropositives after natural SARS-CoV-2 infection presented with a substantially higher antibody response already after dose 1 of BNT162b2, as measured by two CE-marked in vitro diagnostic tests and a sVNT. These results should stimulate discussion and research on whether individuals after previous SARS-CoV-2 infection would benefit from a two-part vaccination schedule or whether these currently much-needed second doses could be saved.

• Dinitrosyl iron complexes (DNICs) as inhibitors of the SARS-CoV-2 main protease - By repurposing DNICs designed for other medicinal purposes, the possibility of protease inhibition was investigated in silico using AutoDock 4.2.6 (AD4) and in vitro via a FRET protease assay. AD4 was validated as a predictive computational tool for coordinatively unsaturated DNIC binding using the only known crystal structure of a protein-bound DNIC, PDB-1ZGN (calculation RMSD = 1.77). From the in silico data the dimeric DNICs TGTA-RRE, [(μ-S-TGTA)Fe(NO)2]2 (TGTA = 1-thio-β-d-glucose…

• Dentistry pathways of coronaviruses transmission: a review - The nCoV-19 in a short period of time, in lower than two months has been spread as a pandemic in all over the world. This novel type of Coronavirus which shows itself with coughing, sneezing, fatigue and respiratory symptoms which is similar to cold illness has killed more than 100,000 people. However, many protocols have been established to minimize the number of infected people, but without any border and regardless the nationality, this virus has been spread in all countries. In this review,…

• Characterization of the Modulatory Effect of Hydroxychloroquine on ACE2 Activity: New Insights in relation to COVID-19 - Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown the ability to inhibit in vitro viral replications of coronaviridae viruses such as SARS-CoV and SARS-CoV-2. However, clinical trial outcomes have been disparate, suggesting that CQ and HCQ antiviral mechanisms are not fully understood. Based on three-dimensional structural similarities between HCQ and the known ACE2 specific inhibitor MLN-4760, we compared their modulation on ACE2 activity. Here we describe, for the first time, in a…

• A Review on Expression, Pathological Roles, and Inhibition of TMPRSS2, the Serine Protease Responsible for SARS- CoV-2 Spike Protein Activation - SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, uses the host cell membrane receptor angiotensin- converting enzyme 2 (ACE2) for anchoring its spike protein, and the subsequent membrane fusion process is facilitated by host membrane proteases. Recent studies have shown that transmembrane serine protease 2 (TMPRSS2), a protease known for similar role in previous coronavirus infections, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), is…

• Multi-omic profiling of plasma reveals molecular alterations in children with COVID-19 - Rationale: Children usually develop less severe symptoms responding to Coronavirus Disease 2019 (COVID-19) than adults. However, little is known about the molecular alterations and pathogenesis of COVID-19 in children. Methods: We conducted plasma proteomic and metabolomic profilings of the blood samples of a cohort containing 18 COVID-19-children with mild symptoms and 12 healthy children, which were enrolled from hospital admissions and outpatients, respectively. Statistical analyses were…

• Mutations in SARS-CoV-2 ORF8 Altered the Bonding Network With Interferon Regulatory Factor 3 to Evade Host Immune System - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been continuously mutating since its first emergence in early 2020. These alterations have led this virus to gain significant difference in infectivity, pathogenicity, and host immune evasion. We previously found that the open-reading frame 8 (ORF8) of SARS-CoV-2 can inhibit interferon production by decreasing the nuclear translocation of interferon regulatory factor 3 (IRF3). Since several mutations in ORF8 have been observed,…

• Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage - So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty- four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block…

From Patent Search

• Camellia nitidissima C.W.Chi Caffeine and Chlorogenic acid composition for anti-SARS-CoV-2 and preparation method and application thereof - - link

• A Novel Method COVID -19 infection using Deep Learning Based System - - link

• 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

• 一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用 - 本发明提供了一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用，涉及生物医药技术领域。本发明利用A型流感病毒八个基因片段为骨架包装出带有新型冠状病毒SARS‑CoV‑2表面刺突蛋白受体结合域（SARS‑CoV‑2_RBD）片段的重组流感病毒，此重组流感病毒可在复制过程中表达具有生物学活性和免疫原性的刺突蛋白受体结合区域RBD。本发明所述重组流感病毒rgH1N1（PR8）‑PA‑RBD可作为重组病毒类药物，用于2019新型冠状病毒肺炎（COVID‑19）的预防；也可作为体外SARS‑COV‑2 RBD等相关抗原表达和体内递呈系统。 - link

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

• 新型冠状病毒B.1.525尼日利亚突变株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.1.525尼日利亚突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.525尼日利亚突变株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.1.525尼日利亚突变株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.1.525尼日利亚突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B.1.525尼日利亚突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - 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