Covid-19 Sentry

Contents

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

From Preprints

• A Novel Artificial Intelligence and Machine learning-based scoring system for evaluating re-purposing potential of Valproic Acid drug in COVID-19. -
  Background Despite widespread vaccinations and the introduction of many repurposed medications, the rise of COVID-19 reinfection due to the SARS-CoV Omicron (B.1.1.529) variant has presented a significant challenge to health authorities across the world. There is a critical need for novel healthcare medications. Valproic acid (VPA) has been reported to be a beneficial drug due to its excellent property to hinder enveloped viral multiplication. Artificial Intelligence (AI) and Machine Learning (ML) have been used extensively to predict the repurposing potential of a drug by examining its past couple of years’ activity. The strategies for drug repositioning that will play a substantial role in this approach can be widely categorized into AI approaches, network-based models, and structure-based approaches. Methodology We have implemented a multimodal pipeline that operates on computational and machine learning strategies, namely molecular docking, molecular data, chemical information, clinical data, and gene expression to analyze the drugs for their sensitivity against covid-19. Here, we implemented the COV-DrugX pipeline to comprehend the physicochemical properties of VPA interactions with viral protein (targets), identify a place in the gene expression profile, additionally its potential role in human network databases. Result and Conclusion Here, we have analyzed the ML pipeline developed by our research group (Rawal et al., 2021) to identify the COVID-associated drug repurposing properties through AI and learning prediction module and use the COV-DrugX pipeline, that predicts the repurposing properties between different existing COVID-19 drugs. Nsp13 was found to have the highest binding affinity (-5.6 kcal/mol) with VPA. By using different modules, we have found that VPA displays physicochemical, biological, and other characteristics similar to existent COVID-19 drugs.
  🖺 Full Text HTML: A Novel Artificial Intelligence and Machine learning-based scoring system for evaluating re-purposing potential of Valproic Acid drug in COVID-19.
• Chronic alcohol intake regulates expression of SARS-CoV2 infection-relevant genes in an organ-specific manner -
  Chronic alcohol consumption and alcohol use disorder (AUD) have a tremendous impact on the patients psychological and physiological health. There is some evidence that chronic alcohol consumption influences SARS-CoV2 infection risk, but the molecular mechanism is unknown. Here, we generated expression data of SARS-CoV2 infection relevant genes (Ace2, Tmprss2 and Mas) in different organs in rat models of chronic alcohol exposure and alcohol dependence. ACE2 and TMPRSS2 represent the virus entry point whereas Mas is activating the anti-inflammatory response once the cells are infected. Across three different chronic alcohol test conditions, we found a consistent up-regulation of Ace2 in the lung, which is the most affected organ in Covid-19 patients. Other organs such as liver, ileum, kidney, heart, and the brain showed also up-regulation of Ace2 and Mas but in a less consistent manner across the different animal models, while Tmprss2 was unaffected in all conditions. We suggest that alcohol-induced upregulation of Ace2 can lead to an elevated stochastic probability of cellular virus entry and may thus confer a molecular risk factor for a SARS-CoV2 infection.
  🖺 Full Text HTML: Chronic alcohol intake regulates expression of SARS-CoV2 infection-relevant genes in an organ-specific manner
• Metabolic dyshomeostasis induced by SARS-CoV-2 structural proteins reveals immunological insights into viral olfactory interactions -
  One of the most common symptoms in COVID-19 is a sudden loss of smell. SARS-CoV-2 has been detected in the olfactory bulb (OB) from animal models and sporadically in COVID-19 patients. To decipher the specific role over the SARS-CoV-2 proteome at olfactory level, we characterized the in-depth molecular imbalance induced by the expression of GFP-tagged SARS-CoV-2 structural proteins (M, N, E, S) on mouse OB cells. Transcriptomic and proteomic trajectories uncovered a widespread metabolic remodeling commonly converging in extracellular matrix organization, lipid metabolism and signaling by receptor tyrosine kinases. The molecular singularities and specific interactome expression modules were also characterized for each viral structural factor. The intracellular molecular imbalance induced by each SARS-CoV-2 structural protein was accompanied by differential activation dynamics in survival and immunological routes in parallel with a differentiated secretion profile of chemokines in OB cells. Machine learning through a proteotranscriptomic data integration uncovered TGF-beta signaling as a confluent activation node by the SARS-CoV-2 structural proteome. Taken together, these data provide important avenues for understanding the multifunctional immunomodulatory properties of SARS-CoV-2 M, N, S and E proteins beyond their intrinsic role in virion formation, deciphering mechanistic clues to the olfactory inflammation observed in COVID-19 patients.
  🖺 Full Text HTML: Metabolic dyshomeostasis induced by SARS-CoV-2 structural proteins reveals immunological insights into viral olfactory interactions
• Intracellular flow cytometry complements RT-qPCR detection of circulating SARS-CoV-2 variants of concern -
  Despite the efficacy of current vaccines against SARS-CoV-2, the spread of the virus is still not under control, as evidenced by the ongoing circulation of the highly contagious SARS-CoV-2 Omicron variant. Basic and antiviral research on SARS-CoV-2 relies on cellular assays of virus replication in vitro. In addition, accurate detection of virus-infected cells and released virus particles is needed to study virus replication and to profile new candidate antiviral drugs. Here, by flow cytometry, we detect SARS-CoV-2 infection at single cell level and distinguish infected Vero E6 cells from uninfected bystander cells. Furthermore, based on the viral nucleocapsid expression, subpopulations of infected cells that are in an early or late phase of viral replication can be differentiated. Importantly, this flow cytometric technique complements RT-qPCR detection and can be applied to all current SARS-CoV-2 variants of concern, including the highly mutated Omicron variant.
  🖺 Full Text HTML: Intracellular flow cytometry complements RT-qPCR detection of circulating SARS-CoV-2 variants of concern
• USP22 controls type III interferon signaling and SARS-CoV-2 infection through activation of STING -
  Pattern recognition receptors (PRRs) and interferons (IFNs) serve as essential antiviral defense against SARS- CoV-2, the causative agent of the COVID-19 pandemic. Type III IFN (IFN-lambda) exhibit cell-type specific and long- lasting functions in autoinflammation, tumorigenesis and antiviral defense. Here, we identify the deubiquitinating enzyme USP22 as central regulator of basal IFN-lambda secretion and SARS-CoV-2 infections in human intestinal epithelial cells (hIECs). USP22-deficient hIECs strongly upregulate genes involved in IFN signaling and viral defense, including numerous IFN-stimulated genes (ISGs), with increased secretion of IFN-lambda and enhanced STAT1 signaling, even in the absence of exogenous IFNs or viral infection. Interestingly, USP22 controls basal and cGAMP-induced STING activation and loss of STING reversed STAT activation and ISG and IFN-lambda expression. Intriguingly, USP22-deficient hIECs are protected against SARS-CoV-2 infection, viral replication and the formation of de novo infectious particles, in a STING- dependent manner. These findings reveal USP22 as central host regulator of STING and type III IFN signaling, with important implications for SARS-CoV-2 infection and antiviral defense.
  🖺 Full Text HTML: USP22 controls type III interferon signaling and SARS-CoV-2 infection through activation of STING
• Design and development of potent h-ACE2 derived peptide mimetics in SARS-CoV-2 Omicron variant therapeutics -
  The pandemic of COVID- 19 has become the global health challenge due to the emergence of new variants. The Receptor binding domain (RBD) of spike protein that makes direct interaction with ACE-2 has shown unique mutated residues in most of the variants of concern (VOC). Recently WHO declared the Omicron (B.1.1.529) as VOC considering it as a highly mutated variant which includes a total of 60 mutations out of which 15 mutations occurred in RBD region of SARS-CoV-2. Inhibition of Protein-protein (Omicron RBD-h-ACE2) interaction was already proved to inhibit the viral infection. In this study, by using molecular dynamic simulations efforts are made to explore the atomistic details of Omicron RBD-h- ACE2 interaction. Based on MD simulations, h-ACE2 motif is found to be interacting with omicron RBD domain. Interaction analysis had provided key residues interacting with Omicron-RBD that helped to extract h-ACE2 peptide. Here, rational design of the peptides that have resemblance with h-ACE2 is done and the peptide library is subjected for inhibition studies against Omicron-RBD. The current study helped to identify the significant peptides that can inhibit Omicron-RBD. Altogether the performed studies will provide an opportunity to develop potential therapeutic peptidomimetics effective against Omicron variant of SARS-CoV-2.
  🖺 Full Text HTML: Design and development of potent h-ACE2 derived peptide mimetics in SARS-CoV-2 Omicron variant therapeutics
• Patterns of Volatility Across the Spike Protein Accurately Predict the Emergence of Mutations within SARS-CoV-2 Lineages -
  New lineages of SARS-CoV-2 are constantly emerging. They contain mutations in the spike glycoprotein that can affect virus infectivity, transmissibility, or sensitivity to vaccine-elicited antibodies. Here we show that the emergence of new spike variants is accurately predicted by patterns of amino acid variability (volatility) in small virus clusters that phylogenetically-precede or chronologically-predate such events. For each spike position, volatility within the virus clusters, volatility at adjacent positions on the three-dimensional structure of the protein, and volatility across the network of co-volatile sites describe its likelihood for mutations. By combining these variables, early-pandemic sequences accurately forecasted mutations in lineages that appeared 6-13 months later. The patterns of mutations in variants Alpha and Delta, as well as the recently-appearing variant Omicron were also predicted remarkably well. Importantly, probabilities assigned to spike positions for within-lineage mutations were lineage-specific, and accurately forecasted the observed changes. Sufficient antecedent warning of the imminent changes in SARS-CoV-2 lineages will allow design of immunogens that address their specific antigenic properties.
  🖺 Full Text HTML: Patterns of Volatility Across the Spike Protein Accurately Predict the Emergence of Mutations within SARS-CoV-2 Lineages
• Why SARS-CoV-2 Omicron variant is milder? A single high-frequency mutation of structural envelope protein matters. -
  SARS-CoV-2 Omicron variant is highly transmissible and extensive morbidity, which has raised concerns for antiviral therapy. In addition, the molecular basis for the attenuated pathogenicity and replication capacity of Omicron remains elusive. Here, we report for the first time that a high-frequency mutation T9I on 2-E of SARS-CoV-2 variant Omicron forms a non-selective ion channel with abolished calcium permeability and reduced acid sensitivity compared to the WT channel. In addition, T9I caused less cell death and a weaker cytokine production. The channel property changes might be responsible for the Omicron variant releases less efficiently and induces a comparatively lower level of cell damage in the infected cells. Our study gives valuable insights into key features of the Omicron variant, further supporting 2-E is a promising drug target against SARS-CoV-2 and providing critical information for the COVID-19 treatment.
  🖺 Full Text HTML: Why SARS-CoV-2 Omicron variant is milder? A single high-frequency mutation of structural envelope protein matters.
• CLEC5A and TLR2 are critical in SARS-CoV-2-induced NET formation and lung inflammation -
  Coronavirus-induced disease 19 (COVID-19) infects more than three hundred and sixty million patients worldwide, and people with severe symptoms frequently die of acute respiratory distress syndrome (ARDS). Autopsy demonstrates the presence of thrombosis and microangiopathy in the small vessels and capillaries. Recent studies indicated that excessive neutrophil extracellular traps (NETs) contributed to immunothrombosis, thereby leading to extensive intravascular coagulopathy and multiple organ dysfunction. Thus, understanding the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced NET formation would be helpful to reduce thrombosis and prevent ARDS. It has been shown that sera from individuals with COVID-19 triggered NET release in vitro, and spleen tyrosine kinase (Syk) inhibitor R406 inhibited NETosis caused by COVID-19 plasma. However, the serum components responsible for NET formation are still unknown. In this study, we found that virus-free extracellular vesicles (EVs) from COVID-19 patients (COVID-19 EVs) induced robust NET formation via Syk-coupled C-type lectin member 5A (CLEC5A). Blockade of CLEC5A inhibited COVID-19 EVs-induced NETosis, and simultaneous blockade of CLEC5A and TLR2 further suppressed SARS-CoV-2-induced NETosis in vitro. Moreover, thromboinflammation and lung fibrosis were attenuated dramatically in clec5a-/-/tlr2-/- mice. These results suggest that COVID-19 EVs play critical roles in SARS-CoV-2-induced immunothrombosis, and blockade of CLEC5A and TLR2 is a promising strategy to inhibit SARS-CoV-2-induced intravascular coagulopathy and reduce the risk of ARDS in COVID-19 patients.
  🖺 Full Text HTML: CLEC5A and TLR2 are critical in SARS- CoV-2-induced NET formation and lung inflammation
• Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study -

  Human coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has multiple neurological consequences, but its long-term effect on brain health is still uncertain. The cerebrovascular consequences of COVID-19 may also affect brain health. Here we assess cerebrovascular health in 45 hospitalised patients using the resting state fluctuation amplitudes (RSFA) from functional magnetic resonance imaging, in relation to disease severity and in contrast with 42 controls. Widespread changes in frontoparietal RSFA were related to the severity of the acute COVID-19 episode, as indexed by COVID-19 WHO Progression Scale, inflammatory and coagulatory biomarkers. This relationship was not explained by chronic cardiorespiratory dysfunction, age, or sex. Exploratory analysis suggests that the level of cerebrovascular dysfunction is associated with cognitive, mental, and physical health at follow-up. The principal findings were consistent across univariate and multivariate approaches. The results indicate chronic cerebrovascular impairment following severe acute COVID-19, with the potential for long-term consequences on cognitive function and mental wellbeing.

  🖺 Full Text HTML: Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study
• Understanding of and Trust in the Centers for Disease Control and Prevention’s Revised COVID-19 Isolation and Quarantine Guidance Among US Adults -

  On December 27, 2021 the Centers for Disease Control and Prevention (CDC) announced changes to their guidance for individuals who are exposed to or test positive for COVID-19. The revised recommendations have prompted widespread discussion of both the scientific rationale and communication strategy, including criticism from the American Medical Association. In this survey study, we assessed understanding of and trust in the CDC9s initial public statement about the new guidance among US adults.

  🖺 Full Text HTML: Understanding of and Trust in the Centers for Disease Control and Prevention’s Revised COVID-19 Isolation and Quarantine Guidance Among US Adults
• The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta- analysis -

  Coronavirus disease 2019 (COVID-19) is accompanied by activated immune-inflammatory pathways and oxidative stress, which both may induce indoleamine-2,3-dioxygenase (IDO), a key enzyme of the tryptophan (TRP) catabolite (TRYCAT) pathway. The aim of the current study was to systematically review and meta-analyze the TRYCAT pathway status including levels of TRP and kynurenine (KYN) and IDO activity, as assessed using the KYN/TRP ratio. This systematic review was performed in December 2021 and searched data in PubMed, Google Scholar, and Web of sciences. In our meta- analysis we included 14 articles which examine TRP and TRYCATs in COVID-19 patients versus non-COVID-19 controls, and severe/critical versus mild/moderate COVID-19. Overall, the analysis was performed on 1269 individuals, namely 794 COVID-19 patients and 475 controls. The results show a significant (p <0.0001) increase in the KYN/TRP ratio (standardized mean difference, SMD=1.099, 95% confidence interval, CI: 0.714; 1.484) and KYN (SMD= 1.123, 95% CI: 0.730;1.516) and significantly lower TRP ((SMD= -1.002, 95%CI: -1.738; -0.266) in COVID-19 versus controls. The KYN/TRP ratio (SMD= 0.945, 95%CI: 0.629; 1.262) and KYN (SMD= 0.806, 95%CI: 0.462; 1.149) were also significantly (p <0.001) higher and TRP lower (SMD= -0.909, 95% CI: -1.569; -0.249) in severe/critical versus mild/moderate COVID-19. No significant difference was detected in the kynurenic acid (KA)/KYN ratio and KA between COVID-19 patients and controls. Our results indicate increased activity of the IDO enzyme in COVID-19 and in severe/critical patients. The TRYCAT pathway is probably implicated in the pathophysiology and progression of COVID-19 and may signal a worse outcome of the disease.

  🖺 Full Text HTML: The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis
• Rapid, high throughput, automated detection of SARS-CoV-2 neutralizing antibodies against native-like vaccine and delta variant spike trimers -

  Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of hACE-2 binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using vaccine and delta variant viral strains showed strong correlation with cell-based pseudovirus and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta variant resistance to neutralization in samples with paired vaccine and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.

  🖺 Full Text HTML: Rapid, high throughput, automated detection of SARS-CoV-2 neutralizing antibodies against native-like vaccine and delta variant spike trimers
• Durability of Omicron-neutralizing serum activity following mRNA booster immunization in elderly individuals -

  Elderly individuals are at high risk for severe COVID-19. Due to modest vaccine responses compared to younger individuals and the time elapsed since prioritized vaccinations, the emerging immune-evasive Omicron variant of SARS- CoV-2 is a particular concern for the elderly. Here we longitudinally determined SARS-CoV-2-neutralizing serum activity against different variants in a cohort of 37 individuals with a median age of 82 years. Participants were followed for 10 months after an initial two-dose BNT162b2 vaccination and up to 4.5 months after a BNT162b2 booster. Detectable Omicron-neutralizing activity was nearly absent after two vaccinations but elicited in 89% of individuals by the booster immunization. Neutralizing titers against the Wu01, Delta, and Omicron variants showed similar post-boost declines and 81% of individuals maintained detectable activity against Omicron. Our study demonstrates the mRNA booster effectiveness in inducing anti-Omicron activity and provides critical information on vaccine response durability in the highly vulnerable elderly population.

  🖺 Full Text HTML: Durability of Omicron-neutralizing serum activity following mRNA booster immunization in elderly individuals
• SARS-CoV-2 RT-qPCR testing of pooled saliva samples: a case study of 824 asymptomatic individuals and a questionnaire survey in Japan -

  From the beginning of the COVID-19 pandemic, the demand for diagnostic and screening tests has exceeded supply. Although the proportion of vaccinated people has increased in wealthier countries, breakthrough infections have occurred amid the emergence of new variants. Pooled-sample COVID-19 testing using saliva has been proposed as an efficient, inexpensive, and non-invasive method to allow larger-scale testing, especially in a screening setting. In this study, we aimed to evaluate pooled RT-qPCR saliva testing and to compare the results with individual tests. Employees of Philips Japan, Ltd. were recruited to participate in COVID-19 screening from October to December 2020. Asymptomatic individuals (n=824) submitted self-collected saliva samples. Samples were tested for the presence of SARS-CoV-2 by RT-qPCR in both 10-sample pools and individual tests. We also surveyed participants regarding their thoughts and behaviors after the PCR screening project. Two of the 824 individuals were positive by RT-qPCR. In the pooled testing, one of these two had no measurable Ct value, but showed an amplification trend at the end of the PCR cycle. Both positive individuals developed cold-like symptoms, but neither required hospitalization. Of the 824 participants, 471 responded to our online questionnaire. Overall, while respondents agreed that PCR screening should be performed regularly, the majority were willing to undergo PCR testing only when it was provided for free or at low cost. In conclusion, pooled testing of saliva samples can support frequent large-scale screening that is rapid, efficient, and inexpensive.

  🖺 Full Text HTML: SARS-CoV-2 RT-qPCR testing of pooled saliva samples: a case study of 824 asymptomatic individuals and a questionnaire survey in Japan

From Clinical Trials

• A Study to Evaluate the Safety, Tolerability, and Immunogenicity of MVC-COV1901 or MVC-COV1901(Beta) Against COVID-19 - Condition:   COVID-19 Vaccine
  Interventions:   Biological: MVC-COV1901(Beta);   Biological: MVC- COV1901
  Sponsor:   Medigen Vaccine Biologics Corp.
  Not yet recruiting

• Exercise Fatigue Parameters and Endothelial Function in Pediatric Patients With a History of COVID-19 Infection or MIS-C - Conditions:   COVID-19;   MIS-C Associated With COVID-19
  Interventions:  
  Device: Cardiopulmonary exercise test (CPET);   Device: Peripheral Arterial Tonography (PAT) using the EndoPAT™ device;   Diagnostic Test: Endothelin
  Sponsors:   Rambam Health Care Campus;   The Baruch Padeh Medical Center, Poriya
  Recruiting

• Evaluate the Efficacy and Safety of TF0023 in Treatments for COVID-19 in Hospitalized Adults - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: TF0023
  Sponsor:  
  Techfields Inc
  Not yet recruiting

• Immunogenicity of an Inactivated COVID-19 Vaccine - Condition:   COVID-19
  Intervention:   Biological: Inactivated COVID-19 Vaccine
  Sponsor:   Sinovac Research and Development Co., Ltd.
  Recruiting

• Short Daily Versus Conventional Hemodialysis for COVID-19 Patients - Condition:   COVID-19
  Intervention:   Other: Short daily dialysis
  Sponsor:  
  Shahid Beheshti University of Medical Sciences
  Completed

• Non-inferiority Trial on Monoclonal Antibodies in COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Bamlanivimab Etesevimab;   Drug: Sotrovimab;   Drug: Casirivimab-Imdevimab
  Sponsors:   Azienda Ospedaliera Universitaria Integrata Verona;   Agenzia Italiana del Farmaco;   Azienda Sanitaria-Universitaria Integrata di Udine
  Recruiting

• Availability and Advice on Test Uptake During the COVID-19 Pandemic: a Vignette Study. - Condition:   COVID-19
  Interventions:   Behavioral: Customised testing advice;   Behavioral: Regular testing advice;   Behavioral: LFT available;   Behavioral: No LFT available
  Sponsor:  
  National Institute for Public Health and the Environment (RIVM)
  Completed

• Efficacy and Safety of Ingavirin®, 90 mg Capsules in Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Ingavirin®, 90 mg capsules;   Drug: Placebo
  Sponsor:   Valenta Pharm JSC
  Recruiting

• Phase IIa Randomized Placebo Controlled Clinical Study of Codivir in Hospitalized Patients With Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Covidir injections;   Diagnostic Test: Quantitative PCR SARS-CoV-2;   Diagnostic Test: IgM and IgG dosage;   Diagnostic Test: Screening Blood tests;   Diagnostic Test: Electrocardiogram;   Other: NEWS-2 score;   Other: WHO score;   Other: Physical examination;   Other: COVID-19-Related Symptoms assessment
  Sponsor:   Code Pharma
  Recruiting

• Exercise in Adults With Post-Acute Sequelae of SARS-CoV-2 (COVID-19) Infection Study - Condition:   COVID-19
  Intervention:   Other: Exercise Prescription
  Sponsor:  
  Baylor Research Institute
  Not yet recruiting

• Safety and Immunogenicity Study of EgyVax Vaccine Candidate for Prophylaxis of COVID-19 Infection - Condition:   COVID-19
  Interventions:   Drug: EgyVax Vaccine Candidate;   Drug: Placebo
  Sponsors:   Eva Pharma;   Veterinary Serum & Vaccine Research Institute (VSVRI), Egypt;   The Supreme Council of University Hospitals, Egypt;   Ministry of Higher Education and Scientific Research, Egypt
  Not yet recruiting

• To Evaluate Safety & Immunogenicity of DelNS1-2019-nCoV-RBD-OPT1 for COVID-19 in Healthy Adults Received 2 Doses of BNT162b2 - Condition:   Covid19
  Interventions:   Biological: DelNS1-2019-nCoV-RBD-OPT1;   Biological: Matching placebo
  Sponsor:   The University of Hong Kong
  Not yet recruiting

• Intranasal Heparin Treatment to Reduce Transmission Among Household Contacts of COVID 19 Positive Adults and Children - Condition:   COVID-19
  Interventions:   Drug: unfractionated heparin;   Drug: 0.9%sodium chloride
  Sponsors:   Murdoch Childrens Research Institute;   University of Melbourne;   Northern Hospital, Australia;   Monash University;   The Peter Doherty Institute for Infection and Immunity;   St Vincent’s Hospital Melbourne
  Not yet recruiting

• Telehealth Exercise Training in Post-COVID Patients - Condition:   COVID-19
  Interventions:   Device: Home-based telehealth exercise training program;   Behavioral: Education and self-exercise
  Sponsor:   Tri-Service General Hospital
  Recruiting

• Heterologous Boost Immunization With an Aerosolised Ad5-nCoV After Two-dose Priming With an Inactivated SARS-CoV-2 Vaccine - Condition:   COVID-19
  Interventions:   Biological: Aerosolized Ad5-nCoV;   Biological: Inactivated SARS-CoV-2 vaccine
  Sponsor:   Jiangsu Province Centers for Disease Control and Prevention
  Recruiting

From PubMed

• Colchicine Against SARS-CoV-2 Infection: What is the Evidence? - Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of concern worldwide and a huge challenge for rheumatologists. Indeed, several antirheumatic drugs are currently used at different stages of COVID-19, such as several cytokine inhibitors and colchicine. Colchicine is one of the oldest medicines with potent anti-inflammatory properties. In rheumatic diseases it is widely used for the treatment of gout, calcium pyrophosphate…

• PI3K/Akt/mTOR pathway: a potential target for anti-SARS-CoV-2 therapy - Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A single-stranded RNA virus from a β-Coronaviridae family causes acute clinical manifestations. Its high death rate and severe clinical symptoms have turned it into the most significant challenge worldwide. Up until now, several effective COVID-19 vaccines have been designed and marketed, but our data on specialized therapeutic drugs for the treatment of COVID-19 is…

• A multiple-step in silico screening protocol to identify allosteric inhibitors of Spike-hACE2 binding - While the COVID-19 pandemic continues to worsen, effective medicines that target the life cycle of SARS-CoV-2 are still under development. As more highly infective and dangerous variants of the coronavirus emerge, the protective power of vaccines will decrease or vanish. Thus, the development of drugs, which are free of drug resistance is direly needed. The aim of this study is to identify allosteric binding modulators from a large compound library to inhibit the binding between the Spike…

• Structural and energetic features of the dimerization of the main proteinase of SARS-CoV-2 using molecular dynamic simulations - The COVID-19 pandemic caused by SARS-CoV-2 has been declared a global health crisis. The development of anti-SARS-CoV-2 drugs heavily depends on the systematic study of the critical biological processes of key proteins of coronavirus among which the main proteinase (M^(pro)) dimerization is a key step for virus maturation. Because inhibiting the M^(pro) dimerization can efficiently suppress virus maturation, the key residues that mediate dimerization can be treated as targets of drug and…

• Attenuation of SARS-CoV-2 Infection by Losartan in Human Kidney Organoids - COVID-19 associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. The susceptibility of human kidneys to direct SARS-CoV-2 infection and pharmacologic manipulation of the renin-angiotensin II signaling (RAS) pathway modulation of this susceptibility remain poorly characterized. Using induced pluripotent stem cell derived kidney organoids, SARS-CoV-1, SARS-CoV-2 and MERS-CoV tropism, defined by the paired expression of a host receptor…

• Development and Characterization of Antimicrobial Textiles from Chitosan-Based Compounds: Possible Biomaterials Against SARS-CoV-2 Viruses - Novel antiviral cotton fabrics impregnated with different formulations based on Chitosan (CH), citric acid (CA), and Copper (Cu) were developed. CA was selected as a CH crosslinker agent and Cu salts as enhancers of the polymer antimicrobial activity. The characterization of the polymeric-inorganic formulations was assessed by using atomic absorption spectroscopy, X-ray diffraction, Fourier transform infrared and UV-Vis spectroscopy, as well as thermogravimetric analysis. The achieved data…

• Identification of SARS-CoV-2 Papain-like Protease (PLpro) Inhibitors Using Combined Computational Approach - In the current pandemic, finding an effective drug to prevent or treat the infection is the highest priority. A rapid and safe approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 PLpro promotes viral replication and modulates the host immune system, resulting in inhibition of the host antiviral innate immune response, and therefore is an attractive drug target. In this study, we used a combined in silico virtual screening for candidates for SARS-CoV-2 PLpro protease…

• Exploring the inhibitory potential of novel bioactive compounds from mangrove actinomycetes against nsp10 the major activator of SARS-CoV-2 replication - The current study reveals the inhibitory potential of novel bioactive compounds of mangrove actinomycetes against nsp10 of SARS-CoV-2. A total of fifty (50) novel bioactive (antibacterial, antitumor, antiviral, antioxidant, and anti- inflammatory) compounds of mangrove actinomycetes from different chemical classes such as alkaloids, dilactones, sesquiterpenes, macrolides, and benzene derivatives are used for interaction analysis against nsp10 of SARS-CoV-2. The six antiviral agents sespenine,…

• SARS-CoV-2 Inhibitors from Nigella Sativa - The recently encountered severe acute respiratory syndrome coronavirus 2 creates huge predicaments among various countries. Lack of specific treatment of COVID-19 disease demands urgency in drug design against SARS-CoV-2 targets. Nigella sativa the miraculous herb native to South and Southwest Asia and belonging to the family Ranunculaceae, due to its beneficial bioactive properties, was used by us for performing in silico study to analyze the potential of its compounds so that they can target…

• Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules - The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase pattern recognition molecules (PRMs) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of 12 PRMs tested, the long pentraxin 3 (PTX3) and mannose-binding lectin (MBL) bound the viral…

• 5-Iodotubercidin inhibits SARS-CoV-2 RNA synthesis - Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid global emergence of SARS-CoV-2 highlights the importance and urgency for potential drugs to control the pandemic. The functional importance of RNA-dependent RNA polymerase (RdRp) in the viral life cycle, combined with structural conservation and absence of closely related homologs in humans, makes it an attractive…

• Tafenoquine and its derivatives as inhibitors for the Severe Acute Respiratory Syndrome Coronavirus 2 - The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely affected human lives around the world as well as the global economy. Therefore, effective treatments against COVID-19 are urgently needed. Here, we screened a library containing Food and Drug Administration (FDA)-approved compounds to identify drugs that could target the SARS-CoV-2 main protease (M^(pro)), which is indispensable for viral protein maturation and regard as an important therapeutic…

• Co-administration of Favipiravir and the Remdesivir Metabolite GS-441524 Effectively Reduces SARS-CoV-2 Replication in the Lungs of the Syrian Hamster Model - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide since December 2019, causing coronavirus disease 2019 (COVID-19). Although vaccines for this virus have been developed rapidly, repurposing drugs approved to treat other diseases remains an invaluable treatment strategy. Here, we evaluated the inhibitory effects of drugs on SARS-CoV-2 replication in a hamster infection model and in in vitro assays. Favipiravir significantly suppressed virus replication in hamster…

• Gasdermin D Inhibits Coronavirus Infection by Promoting the Noncanonical Secretion of Beta Interferon - Pyroptosis, a programmed cell death, functions as an innate immune effector mechanism and plays a crucial role against microbial invasion. Gasdermin D (GSDMD), as the main pyroptosis effector, mediates pyroptosis and promotes releasing proinflammatory molecules into the extracellular environment through pore-forming activity, modifying inflammation and immune responses. While the substantial importance of GSDMD in microbial infection and cancer has been widely investigated, the role of GSDMD in…

• Vitamin D can reduce severity in COVID-19 through regulation of PD-L1 - COVID-19 is a highly contagious viral infection that has killed millions of people around the world. The most important diagnostic feature of COVID-19 is lymphocyte depletion, particularly the depletion of T cells. In COVID-19 infections, there is a link between destruction of T cells and increased expression of inhibitory immune checkpoint molecules (PD-1/PD-L1) on T cell surfaces. It was shown that PD-1/PD-L1 levels increase in severely COVID-19 infected individuals. Higher proinflammatory…

From Patent Search

• IDENTIFICATION AND ALARM SYSTEM FOR FACIAL CORONA MASK USING CNN BASED IMAGE PROCESSING - tThe covid-19 epidemic is the world’s largest wake-up call for people to pay attention to their own and society’s health. One thing to keep in mind is that there is a segment of the population that has been exposed to the covid-19 virus and has generated antibodies without developing any significant illnesses and is continuing to be healthy. This indicates that a significant section of the population, even excluding the elderly, lacks the necessary bodily immunity to combat a Viral infection. As terrible as covid-19 is on a global scale, developing personal health standards and preventative measures for any pathogenic virus as a community would have spared many lives. In’this work, a camera is combined with an image processing system to recognise facial masks, which may be improved in a variety of ways. First and foremost, this method is meant to identify masks on a single person’s face. While this method is efficient in identifying someone has a mask, it does not ensure that they will wear it all of the time. The most effective update for this task is to install a camera with a wide field of view so that many individuals can be seen in the frame, and the faces of those who aren’t wearing markings can be identified, as well as the number of people and the timing. - link

• ANTIMICROBIAL SANITIZING FORMULATION - An antimicrobial sanitizing formulation, comprising, i) isopropyl alcohol in the range of 0.1%- 80% w/w, ii) an emollient in the range of 0.1%-15% w/w, iii) hydrogen peroxide in the range of 0.1 0.13% w/w, iv) citric acid in the range of 0.1% to 2.0% w/w, v) silver nitrate in the range of 0.1% to 0.5% w/w, and vi) a fragrance imparting agent in the range of 0.1% to 2.0% w/w. - link

• A HEALTH BAND WITH A BIOMETRIC MODULE AND WORKING METHOD THEREOF - The present invention discloses a health band with a biometric module and method thereof. The assembly includes, but not limited to, a plurality of sensors configured to gather health data associated with a predefined symptom of a medical condition of a user; a memory unit configured to store the data and an interface, which is configured to determine the medical condition using the data;a processing unit configured to execute the application; and a notification facility configured to provide a notification upon receiving from the interface an instruction associated with the notification, wherein the notification is associated with a drug reminder and the like. - link

• RNA 검출 방법 - 본 발명은 RNA의 분석 및 검출 방법에 관한 것이다. 특히, 본 발명은 특히, 본 발명은 짧은 염기서열의 RNA까지 분석이 가능하면서도 높은 민감도 및 정확도로 정량적 검출까지 가능하여 감염증, 암 등 여러 질환의 진단 용도로도 널리 활용될 수 있다. - link

• REUNION OF PHOTOTHERMAL THERAPY WITH MXENE ADSORBED UREMIC TOXINS AND CYTOKINES: A SHILED FOR COVID-19 PATENTS - The COVID-19 pandemic has created havoc throughout the world. The disease has proved to be more fatalfor patients having comorbidities like diabetics, lungs and kidney infections, etc. In the case of COVID-19 patientsI having kidney injury, the. removal of uremic toxins from the blood is hindered and there is a rapid surge in the levelj of cytokine hormone resulting in the death of the patient in a short interval of time. To resolve this issue,iI; researchers have examined that the immediate removal of these toxins can improve the condition of the patient to a |greater extent. Studies have also found the presence of SARS CoV-2 viral RNAs in the blood of COVID-19patients, which risks their life as well as impacts the blood transfusion process, especially in the case ofasymptomatic patients. Hence it is required to control the surge of cytokines and uremic toxins as well as disinfectthe blood of the patient from the virus. MXenes, having a foam-like porous structure and hydrophilic negativesurface functionalization have greater adsorption efficiency as well as superior photothermal activity. Utilizingthese properties of MXenes, the MXene membranes can be used in the dialyzer that can help in the efficient andBiuick removal of the uremic toxins, cytokines, and other impurities from the blood. Along with this the greaterTJAdsorption efficiency of MXenes to amino acids result in the trapping of the SARS CoV-2 viruses on the surface J)3>f the MXene. Many researchers as well as the WHO have proved the efficient reduction of the viral copy numbersjjvith the increase of temperature. Hence, followed by the trapping of the viruses, the implementation of"Zphotothermal Therapy can result in the inactivation and denaturation of the viruses and their respective viral RNAsBJlby the produced heat. The same process can be repeated several times to get better results. This whole process canr>oQ-esult in impurity-free and infection-free blood, that can be returned back to the body of the patient or can be!— I Sitilized for the blood transfusion process without any risk of infection.IM - link

• REDUCING AND STOPPING OXYGEN WASTAGE IN HOSPITAL - In an aspect, the present invention discloses a system (200) for prevention and reduction of oxygen wastage from oxygen mask (202). The system (200) includes the oxygen mask (202) having straps; a tension sensor (204), the tension sensor being sensitive towards tension produced in the straps as the oxygen gets leakage through sides of the mask (202); a processor configured in alignment with the tension sensor (204); and a buzzer (206) in alignment with processor. - link

• 编码SARS-COV-2病毒C.37突变株抗原的DNA分子、DNA疫苗及应用 - 本发明涉及生物技术领域，具体而言，提供了一种编码SARS‑COV‑2病毒C.37突变株抗原的DNA分子、DNA疫苗及应用。本发明提供的SEQ ID NO：1核酸序列在真核表达系统中能够高效转录和表达，而且具有免疫原性，表现在体液免疫和细胞免疫应答中，以此作为活性成分的核酸疫苗同样具有良好的免疫原性。 - link

• SARS-COV-2病毒B.1.617.2突变株DNA疫苗及应用 - 本发明涉及生物技术领域，具体而言，提供了一种编码SARS‑COV‑2病毒B.1.617.2突变株抗原的DNA分子、DNA疫苗及应用。本发明提供的SEQ ID NO：1核酸序列在真核表达系统中能够高效转录和表达，而且具有免疫原性，表现在体液免疫和细胞免疫应答中，以此作为活性成分的核酸疫苗同样具有良好的免疫原性。 - link

• Hung Thanh Phan COVID-19 NEW SOLUTION - - link

• A METHOD TO REVEAL MOTIF PATTERNS OF COVID-19 USING MULTIPLE SEQUENCE ALIGNMENT - This present invention consists of different levels of computation and work in a pipeline manner i.e., input of one will be output of another and it is sequential process. Input data given in form of nucleotide sequence (DNA) of different COVID-19 patients (1). Using these nucleotide sequence perform mutation if possible and arrange them in a sequential order (2). Arrange number of nucleotide sequences of different patients in row wise and also compute number of characters in each row. (3). Compute frequency of occurrence of character in column wise and create a matrix having 4 rows and maximum sequence length will be the column size (4). Find the character like A, T, C, and G which one has maximum score and similarly find for each column to produce a final sequence (5). - link