Covid-19 Sentry

Contents

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

From Preprints

• Potential role of host-mediated RNA editing in intra-host variability of SARS-CoV-2 genomes -
  Since its zoonotic transmission in the human host, the SARS-CoV-2 virus has infected millions and has diversified extensively. A hallmark feature of viral system survival is their continuous evolution and adaptation within the host. RNA editing via APOBEC and ADAR family of enzymes has been recently implicated as the major driver of intra-host variability of the SARS-CoV-2 genomes. Analysis of the intra-host single-nucleotide variations (iSNVs) in SARS-CoV-2 genomes at spatio-temporal scales can provide insights on the consequence of RNA editing on the establishment, spread and functional outcomes of the virus. In this study, using 1,347 transcriptomes of COVID-19 infected patients across various populations, we find variable prevalence of iSNVs with distinctly higher levels in Indian population. Our results also suggest that iSNVs can likely establish variants in a population. These iSNVs may also contribute to key structural and functional changes in the Spike protein that confer antibody resistance.
  🖺 Full Text HTML: Potential role of host-mediated RNA editing in intra-host variability of SARS-CoV-2 genomes
• Mutational signatures and heterogeneous host response revealed via large-scale characterization of SARS-CoV-2 genomic diversity -
  To dissect the mechanisms underlying the inflation of variants in the SARS-CoV-2 genome, we present one of the largest up-to-date analyses of intra-host genomic diversity, which reveals that most samples present heterogeneous genomic architectures, due to the interplay between host-related mutational processes and transmission dynamics. The deconvolution of the set of intra-host minor variants unveils the existence of non overlapping mutational signatures related to specific nucleotide substitutions, which prove that distinct hosts respond differently to SARS-CoV-2 infections, and which are likely ruled by APOBEC, Reactive Oxygen Species (ROS) and ADAR. Thanks to a corrected-for-signatures dN/dS analysis we demonstrate that the mutational processes underlying such signatures are affected by purifying selection, with important exceptions. In fact, several mutations linked to low-rate mutational processes appear to transit to clonality in the population, eventually leading to the definition of new clonal genotypes and to a statistically significant increase of overall genomic diversity. Importantly, the analysis of the phylogenetic model shows the presence of multiple homoplasies, due to mutational hotspots, phantom mutations or positive selection, and supports the hypothesis of transmission of minor variants during infections. Overall, the results of this study pave the way for the integrated characterization of intra-host genomic diversity and clinical outcome of SARS-CoV-2 hosts.
  🖺 Full Text HTML: Mutational signatures and heterogeneous host response revealed via large-scale characterization of SARS-CoV-2 genomic diversity
• In silico design of Multi-epitope-based peptide vaccine against SARS-CoV-2 using its spike protein -
  SARS-CoV-2 has been efficient in ensuring that many countries are brought to a standstill. With repercussions ranging from rampant mortality, fear, paranoia, and economic recession, the virus has brought together countries to look at possible therapeutic countermeasures. With prophylactic interventions possibly months away from being particularly effective, a slew of measures and possibilities concerning the design of vaccines are being worked upon. We attempted a structure-based approach utilizing a combination of epitope prediction servers and Molecular dynamic (MD) simulations to develop a multi-epitope-based subunit vaccine that involves the two subunits of the spike glycoprotein of SARS-CoV-2 (S1 and S2) coupled with a substantially effective chimeric adjuvant to create stable vaccine constructs. The designed constructs were evaluated based on their docking with Toll-Like Receptor (TLR) 4. Our findings provide an epitope-based peptide fragment that can be a potential candidate for the development of a vaccine against SARS-CoV-2. Recent experimental studies based on determining immunodominant regions across the spike glycoprotein of SARS-CoV-2 indicate the presence of the predicted epitopes included in this study.
  🖺 Full Text HTML: In silico design of Multi-epitope-based peptide vaccine against SARS-CoV-2 using its spike protein
• Making the invisible enemy visible -
  During the COVID-19 pandemic, structural biologists rushed to solve the structures of the 28 proteins encoded by the SARS-CoV-2 genome in order to understand the viral life cycle and enable structure-based drug design. In addition to the 204 previously solved structures from SARS-CoV-1, 548 structures covering 16 of the SARS-CoV-2 viral proteins have been released in a span of only 6 months. These structural models serve as the basis for research to understand how the virus hijacks human cells, for structure-based drug design, and to aid in the development of vaccines. However, errors often occur in even the most careful structure determination - and may be even more common among these structures, which were solved quickly and under immense pressure. The Coronavirus Structural Task Force has responded to this challenge by rapidly categorizing, evaluating and reviewing all of these experimental protein structures in order to help downstream users and original authors. In addition, the Task Force provided improved models for key structures online, which have been used by Folding@Home, OpenPandemics, the EU JEDI COVID-19 challenge and others.
  🖺 Full Text HTML: Making the invisible enemy visible
• Proteoforms of the SARS-CoV-2 nucleocapsid protein are primed to proliferate the virus and attenuate the antibody response -
  The SARS-CoV-2 nucleocapsid (N) protein is the most immunogenic of the structural proteins and plays essential roles in several stages of the virus lifecycle. It is comprised of two major structural domains: the RNA binding domain, which interacts with viral and host RNA, and the oligomerization domain which assembles to form the viral core. Here, we investigate the assembly state and RNA binding properties of the full-length nucleocapsid protein using native mass spectrometry. We find that dimers, and not monomers, of full-length N protein bind RNA, implying that dimers are the functional unit of ribonucleoprotein assembly. In addition, we find that N protein binds RNA with a preference for GGG motifs which are known to form short stem loop structures. Unexpectedly, we found that N undergoes proteolytic processing within the linker region, separating the two major domains. This process results in the formation of at least five proteoforms that we sequenced using electron transfer dissociation, higher-energy collision induced dissociation and corroborated by peptide mapping. The cleavage sites identified are in highly conserved regions leading us to consider the potential roles of the resulting proteoforms. We found that monomers of N-terminal proteoforms bind RNA with the same preference for GGG motifs and that the oligomeric state of a C-terminal proteoform (N156-419) is sensitive to pH. We then tested interactions of the proteoforms with the immunophilin cyclophilin A, a key component in coronavirus replication. We found that N1-209 and N1-273 bind directly to cyclophilin A, an interaction that is abolished by the approved immunosuppressant drug cyclosporin A. In addition, we found the C-terminal proteoform N156-419 generated the highest antibody response in convalescent plasma from patients >6 months from initial COVID-19 diagnosis when compared to the other proteoforms. Overall, the different interactions of N proteoforms with RNA, cyclophilin A, and human antibodies have implications for viral proliferation and vaccine development.
  🖺 Full Text HTML: Proteoforms of the SARS-CoV-2 nucleocapsid protein are primed to proliferate the virus and attenuate the antibody response
• IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition -
  Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) are thought to restrict numerous viral pathogens including severe acute respiratory syndrome coronaviruses (SARS-CoVs). However, most evidence comes from single-round pseudovirus infection studies of cells that overexpress IFITMs. Here, we verified that artificial overexpression of IFITMs blocks SARS-CoV-2 infection. Strikingly, however, endogenous IFITM expression was essential for efficient infection of genuine SARS-CoV-2 in human lung cells. Our results indicate that the SARS-CoV-2 Spike protein interacts with IFITMs and hijacks them for efficient viral entry. IFITM proteins were expressed and further induced by interferons in human lung, gut, heart and brain cells. Intriguingly, IFITM-derived peptides and targeting antibodies inhibited SARS-CoV-2 entry and replication in human lung cells, cardiomyocytes and gut organoids. Our results show that IFITM proteins are important cofactors for SARS-CoV-2 infection of human cell types representing in vivo targets for viral transmission, dissemination and pathogenesis and suitable targets for therapeutic approaches.
  🖺 Full Text HTML: IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition
• Are the emerging SARS-COV-2 mutations friend or foe? -
  The rapid spread of the virus in the community and the widely applied anti-viral treatments may cause new mutations in the virus. This situation raises concerns that potentially more virulent strains with higher mortality rates or the emergence of treatment-resistant strains. SARS-CoV-2 mutates regularly, acquiring about one new mutation in its genome every two weeks. Following rapid spread the original Wuhan form of the virus globally in early 2020, D614G variant of the virus become the dominant form of the virus. While concerns about the D614G variant continue to be debated, the latest UK variant, N501Y, has sparked serious controversy regarding the evolution of the virus, especially at a time when vaccines were available. In this article, the importance of existing mutations in the virus is analyzed in the light of the available data and predictions for the future are discussed.
  🖺 Full Text HTML: Are the emerging SARS-COV-2 mutations friend or foe?
• Measuring COVID-19 Fear and Threat in Australian, Indian, and Nepali University Students -
  The present study describes the adaption and validation of a brief measure of contagion-related fear and threat in Australian, Indian, and Nepali university students in Australia at the height of the first wave of the COVID-19 pandemic. Adapted from Ho, Kwong-Lo, Mak, and Wong’s (2005) SARS-related fear scale, the Contagion Fear and Threat Scale (CFTS) was rapidly adapted to capture the experience of COVID-19 pandemic-related fear. The factor structure and validity of the 6-item scale were established among Australian (n=155), Indian (n=111), and Nepali (n=148) university students studying in Australia in May-June 2020. Factor analysis revealed two 3-item factors in the Australian student sample: Fear of Infection and Existential Threat. These factors were confirmed in the Indian and Nepali student samples and mirror those found by the Ho et al. (2005) in their original instrument. The convergent and discriminant validity of the full CFTS, Fear of Infection, and Existential Threat scales are indicated via correlations with established measures of depression, anxiety, stress, subjective wellbeing, and religiosity. Differences in the performance of the Fear of Infection and Existential Threat scales are considered in terms of the respective objective and subjective nature of the constructs.
  🖺 Full Text HTML: Measuring COVID-19 Fear and Threat in Australian, Indian, and Nepali University Students
• Receipt, spending, and clinical correlates of economic impact payments among middle and low-income U.S. adults -
  This study examined characteristics and planned expenses of U.S. adults who received the economic impact payment (EIP) during the coronavirus disease 2019 (COVID-19) pandemic. Using a nationally representative sample of 6,607 low and middle-income U.S. adults, this study examined the proportion and correlates of EIP receipt among eligible adults; and associations between planned expenses using the EIP, problems paying expenses, and clinical characteristics. In the total sample, 79% reported they received the EIP and 82% of recipients reported the EIP had a positive impact on their life. Being a veteran (OR= 2.59), married (OR= 1.82), with a history of schizophrenia-spectrum disorder (OR= 1.74) or posttraumatic stress disorder (OR= 1.51), and screening negative for recent suicidal ideation (OR= 0.49) were associated with EIP receipt. Planned expenses using the EIP for savings, paying debt, and rent accounted for 63% of the total amount. Greater planned expenses on substance use or gambling were correlated with lower rated impact of the EIP on life. Additionally, EIP receipt was associated with fewer problems paying daily expenses, but participants who screened positive for mental health or alcohol use problems were more likely to report problems paying daily expenses in the past month. Together, these findings suggest unconditional cash transfers, like the EIP, are important for low and middle-income populations to sustain their living situation. The management of funds are important to consider, especially among those experiencing mental health problems, and may represent opportunities for financial literacy and money management interventions.
  🖺 Full Text HTML: Receipt, spending, and clinical correlates of economic impact payments among middle and low-income U.S. adults
• Māori and Pacific People in New Zealand have higher risk of hospitalisation for COVID-19 -

  Aims. We aim to quantify differences in clinical outcomes from COVID-19 infection by ethnicity with a focus on risk of hospitalisation. Methods. We used data on age, ethnicity, deprivation index, pre-existing health conditions, and clinical outcomes on 1,829 COVID-19 cases reported in New Zealand. We used a logistic regression model to calculate odds ratios for the risk of hospitalisation by ethnicity. We also consider length of hospital stay and risk of fatality. Results. Māori have 2.5 times greater odds of hospitalisation than non-Māori, non-Pacific people, after controlling for age and pre-existing conditions. Similarly, Pacific people have 3 times greater odds. Conclusions. Structural inequities and systemic racism in the healthcare system mean that Māori and Pacific communities face a much greater health burden from COVID-19. Older people and those with pre-existing health conditions are also at greater risk. This should inform future policy decisions including prioritising groups for vaccination.

  🖺 Full Text HTML: Māori and Pacific People in New Zealand have higher risk of hospitalisation for COVID-19
• In silico evaluation of isatin-based derivatives with RNA-dependent RNA polymerase of the novel coronavirus SARS-CoV-2 -
  Isatin (1H-indole-2,3-dione)-containing compounds have been shown to possess several remarkable biological activities. We had previously explored a few isatin-based imidazole derivatives for their predicted dual activity against both inflammation and cancer. We explored 47 different isatin-based derivatives (IBDs) for other potential biological activities using in silico tools and found them to possess anti-viral activity. Using AUTODOCK tools, the binding site, binding energy, inhibitory constant/Ki and receptor-ligand interactions for each of the compounds was analyzed against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). The partition coefficient (logP) values were predicted using MedChem Designer tool. Based on the best Ki, binding energy and the ideal range of logP (between 1.0-3.0), 10 out of total 47 compounds were deemed to be prospective RdRp inhibitors. Some of these compounds gave better Ki, binding energy and logP values when compared to standard RdRp inhibitors such as remdesivir (Ki = 15.61 μM, logP = 2.2; binding energy = -6.95), a clinically approved RdRp inhibitor which is widely used for critical care of COVID-19 patients. The same in silico parameters were assessed for 9 other popular RdRp inhibitors (other than remdesivir), which were earlier used to target RdRp of other viruses, and are now repurposed to target SARS-CoV-2 RdRp. The results showed that the 10 selected isatin-based derivatives (IBDs) could be further explored for activity against SARS-Cov-2. In the present study we evaluated the efficacy of these compounds in silico.
  🖺 Full Text HTML: In silico evaluation of isatin-based derivatives with RNA-dependent RNA polymerase of the novel coronavirus SARS-CoV-2
• Did people really drink bleach to prevent COVID-19? A tale of problematic respondents and a guide for measuring rare events in survey data -

  Society is becoming increasingly dependent on survey research. However, surveys can be impacted by participants who are non-attentive, respond randomly to survey questions, and misrepresent who they are and their true attitudes. The impact that such respondents can have on public health research has rarely been systematically examined. In this study we examine whether Americans began to engage in dangerous cleaning practices to avoid Covid-19 infection. Prior reports have suggested that people began to engage in highly dangerous cleaning practices during the Covid-19 pandemic, including ingesting household cleansers such as bleach. In a series of studies totaling close to 1400 respondents, we show that 80-90% of reports of household cleanser ingestion are made by problematic respondents. These respondents report impossible claims such as "recently having had a fatal heart attack" and "eating concrete for its iron content" at a similar rate to ingesting household cleaners. Additionally, respondents frequent misreading or misinterpreting the intent of questions accounted for the rest of such claims. Once inattentive, mischievous, and careless respondents are taken out of the analytic sample we find no evidence that people ingest cleansers. The relationship between dangerous cleaning practices and health outcomes also becomes non-significant once problematic respondents are taken out of the analytic sample. These results show that reported ingestion of household cleaners and other similar dangerous practices are an artifact of problematic respondent bias. The implications of these findings for public health and medical survey research, as well as best practices for avoiding problematic respondents in surveys are discussed.

  🖺 Full Text HTML: Did people really drink bleach to prevent COVID-19? A tale of problematic respondents and a guide for measuring rare events in survey data
• Relationships of total COVID-19 cases and deaths with ten demographic, economic and social indicators -

  The statistical relationships of total COVID-19 Cases and Deaths per million populations in 45 countries, where 85.8% of the world9s population lives with 10 demographic, economic and social indicators were studied. Data for 28 May 2020 were used in the main calculations. The relationship of Deaths per million population and total Cases per million population is very close and reaches correlation coefficient R = 0.926. It is interesting that the close correlations were found of Cases and Deaths per 1 million with a purely economic index like GDP PPP per capita, where R = 0.687 and R = 0.660, respectively. Even more close correlations were found of Cases and Deaths per 1 million with a composite index HDI, where the correlation coefficients reach 0.724 and 0.680, respectively. The main reason for these paradoxical results is the underestimation of pandemic restrictions in the form of masks, social distance and disinfection in most of these countries. Other indicators (excluding Gini index and Population Density) also show statistically significant correlations with Cases and Deaths per 1 million with correlation coefficients from 0.432 to 0.634. The statistical significance of the found correlations determined using Student9s t-test was p <0.0001. Surprisingly, there was no statistically significant correlation between Cases and Deaths with Population Density. To check whether there is a change in the correlations with the development of the pandemic, a statistical analysis was made for four different dates - 9 April, 28 May, 7 August and 30 November 2020. It was found that the correlation coefficients of COVID-19 cases and Deaths with the rest indicators decrease during the pandemic.

  🖺 Full Text HTML: Relationships of total COVID-19 cases and deaths with ten demographic, economic and social indicators
• The neutralization effect of Montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies -
  Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of SARS-CoV-2. In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist Montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of Montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the Fluorescent Resonance Energy Transfer (FRET)-based main protease enzyme inhibition assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T / hACE2, and virus neutralization assay using xCELLigence MP real time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of the Montelukast both on virus entry into the host cell (Spike/ACE2) and on the main protease enzyme inhibition. The virus neutralization assay results showed that while no cytotoxicity of the Montelukast was observed at 12 micro-molar concentration, the cell index time 50 (CIT50) value was delayed for 12 hours. Moreover, it was also shown that Favipiravir, a well-known antiviral used in COVID-19 therapy, should be used by 16-fold higher concentrations than Montelukast in order to have the same effect of Montelukast. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and if its effect is proven in clinical phase studies, it should be used against COVID-19.
  🖺 Full Text HTML: The neutralization effect of Montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies
• The mechanism of SARS-CoV-2 nucleocapsid protein recognition by the human 14-3-3 proteins -
  The coronavirus nucleocapsid protein (N) controls viral genome packaging and contains numerous phosphorylation sites located within unstructured regions. Phosphorylated SARS-CoV N was shown to bind to the host 14-3-3 protein in the cytoplasm. Proteomic data indicate that seven human 14-3-3 proteins are highly abundant in human tissues vulnerable to SARS-CoV-2 infection, collectively reaching ~1.8% of all proteins in the lungs, ~1.4% in the gastrointestinal system, ~2.3% in the nervous system. Although the association between 14-3-3 and SARS-CoV-2 N proteins can represent one of the key host-pathogen interactions, its mechanism and the specific critical phosphosites were unknown. Here, we show that phosphorylated SARS-CoV-2 N protein (pN) dimers, reconstituted via bacterial co-expression with protein kinase A, directly associate, in a phosphorylation-dependent manner, with the dimeric 14-3-3 protein hub, but not with its monomeric mutant. We demonstrate that pN is recognized by all seven human 14-3-3 isoforms with various efficiencies and determine the apparent KD to selected isoforms in a low micromolar range. Serial truncations pinpointed a critical phosphorylation site to Ser197, located within the SR-rich region of N. The tight 14-3-3/pN association suggests it could regulate nucleocytoplasmic shuttling of N, while hijacking cellular pathways by 14-3-3 sequestration. As such, the assembly may represent a valuable target for therapeutic intervention.
  🖺 Full Text HTML: The mechanism of SARS-CoV-2 nucleocapsid protein recognition by the human 14-3-3 proteins

From Clinical Trials

• 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

• Dendritic Cell Vaccine to Prevent COVID-19 - Condition:   COVID-19
  Intervention:   Biological: AV-COVID-19
  Sponsors:   Indonesia-MoH;   Aivita Biomedical, Inc.;   PT AIVITA Biomedika Indonesia;   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia;   RSUP Dr. Kariadi Semarang, indonesia;   Faculty of Medicine University of Diponegoro, Indonesia
  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

• Inhaled Ivermectin and COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Ivermectin Powder
  Sponsor:   Mansoura University
  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

• Efficacy and Safety of hzVSF-v13 in Patients With COVID-19 Pneumonia - Condition:   COVID-19
  Interventions:   Drug: hzVSF-v13;   Drug: Placebo (Normal saline solution)
  Sponsor:   ImmuneMed, Inc.
  Recruiting

• Efficacy and Safety of hzVSFv13 in Patients With COVID-19 Pneumonia - Condition:   COVID-19
  Interventions:   Drug: hzVSF-v13;   Drug: Placebo (Normal saline solution)
  Sponsor:   ImmuneMed, Inc.
  Not yet 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

• Efficacy and Safety of hzVSF-v13 in Moderate to Severe Patients With COVID-19 Pneumonia - Condition:   COVID-19
  Interventions:   Drug: hzVSF-v13;   Drug: Placebo (Normal saline solution)
  Sponsor:   ImmuneMed, Inc.
  Not yet recruiting

• AZD1222 Vaccine in Combination With rAd26-S, Recombinant Adenovirus Type 26 Component of Gam-COVID-Vac Vaccine, for the Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: AZD1222;   Biological: rAd26-S
  Sponsors:   AstraZeneca;   R-Pharm
  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

• 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

• Efficacy and Safety of Ivermectin for Treatment and Prophylaxis of COVID-19 Pandemic - Condition:   Covid19
  Interventions:   Drug: Ivermectin;   Drug: Hydroxychloroquine;   Behavioral: personal protective Measures
  Sponsor:   Benha University
  Completed

From PubMed

• Effects of Tocilizumab in COVID-19 patients: a cohort study - CONCLUSIONS: Majority of patients demonstrated clinical improvement and were successfully discharged alive from the hospital after receiving tocilizumab. We observed a rebound effect with CRP, which may suggest the need for higher or subsequent doses to adequately manage cytokine storm. Based on our findings, we believe that tocilizumab may have a role in the early treatment of COVID-19, however larger randomized controlled studies are needed to confirm this.

• Gallium maltolate has in vitro antiviral activity against SARS-CoV-2 and is a potential treatment for COVID-19 - CONCLUSION: The in vitro activity of GaM against SARS-CoV-2, together with GaM's known anti-inflammatory activity, provide justification for testing GaM in COVID-19 patients.

• Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform - BACKGROUND: Hydroxychloroquine has been shown to inhibit entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into epithelial cells in vitro, but clinical studies found no evidence of reduced mortality when treating patients with COVID-19. We aimed to evaluate the effectiveness of hydroxychloroquine for prevention of COVID-19 mortality, as opposed to treatment for the disease.

• Identification of FDA approved drugs and nucleoside analogues as potential SARS-CoV-2 A1pp domain inhibitor: An in silico study - Coronaviruses are known to infect respiratory tract and intestine. These viruses possess highly conserved viral macro domain A1pp having adenosine diphosphate (ADP)-ribose binding and phosphatase activity sites. A1pp inhibits adenosine diphosphate (ADP)-ribosylation in the host and promotes viral infection and pathogenesis. We performed in silico screening of FDA approved drugs and nucleoside analogue library against the recently reported crystal structure of SARS-CoV-2 A1pp domain. Docking...

• Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA - Self-amplifying RNA (saRNA) is a cutting-edge platform for both nucleic acid vaccines and therapeutics. saRNA is self-adjuvanting, as it activates types I and III interferon (IFN), which enhances the immunogenicity of RNA vaccines but can also lead to inhibition of translation. In this study, we screened a library of saRNA constructs with cis-encoded innate inhibiting proteins (IIPs) and determined the effect on protein expression and immunogenicity. We observed that the PIV-5 V and Middle East...

• Structure-Based Screening to Discover New Inhibitors for Papain-like Proteinase of SARS-CoV-2: An In Silico Study - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) expresses a multifunctional papain-like proteinase (PLpro), which mediates the processing of the viral replicase polyprotein. Inhibition of PLpro has been shown to suppress the viral replication. This study aimed to explore new anti-PLpro candidates by applying virtual screening based on GRL0617, a known PLpro inhibitor of SARS coronavirus (SARS-CoV). The three-dimensional (3D) structure of SARS-CoV-2 PLpro was built by homology...

• A ligand selection strategy identifies chemical probes targeting the proteases of SARS-CoV-2 - Activity-based probes are valuable tools for chemical biology. However, finding probes that specifically target the active site of an enzyme remains a challenging task. Here we present a ligand selection strategy that allows to rapidly tailor electrophilic probes to a target of choice and showcase its application for the two cysteine proteases of SARS-CoV-2 as proof of concept. The resulting probes were specific for the active site labelling of 3CL pro and PL pro with sufficient selectivity in a...

• Spiky nanostructures for virus inhibition and infection prevention - The outbreak of a novel highly infectious virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has aroused people's concern about public health. The lack of ready-to-use vaccines and therapeutics makes the fight with these pathogens extremely difficult. To this point, rationally designed virus entry inhibitors that block the viral interaction with its receptor can be novel strategies to prevent virus infection. For ideal inhibition of the virus, the virus-inhibitor interaction...

• The SARS-CoV-2 RNA-protein interactome in infected human cells - Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome...

• Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension - The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to >200 countries posing a global public health concern. Patients with comorbidity, such as hypertension suffer more severe infection with elevated mortality. The development of effective antiviral drugs is in urgent need to treat COVID-19 patients. Here, we report that calcium channel blockers (CCBs), a type of antihypertensive drug that is widely used in clinics,...

• Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus - CONCLUSION: The results showed that INAE alleviated IAV induced ALI in mice. The mechanisms of INAE were associated with its anti-influenza, anti-inflammatory and anti-oxidation properties. Indigo Naturalis might have clinical potential to treat ALI induced by IAV.

• Action of dipeptidyl peptidase-4 inhibitors on SARS-CoV-2 main protease - In a recent publication in this journal Eleftheriou et al. proposed inhibitors of dipeptidyl peptidase-4 (DPP-4) to be functional inhibitors of the main protease (M pro ) of SARS-CoV-2. Their predictions prompted the authors to suggest linagliptin, a DPP-4 inhibitor and approved anti-diabetes drug, as a repurposed drug candidate against the ongoing COVID-19 pandemic. We used an enzymatic assay measuring inhibition of M pro catalytic activity in the presence of four different commercially...

• "Silent hypoxaemia in COVID-19 patients" - The clinical presentation of COVID-19 due to infection with SARS-CoV-2 is highly variable with the majority of patients having mild symptoms while others develop severe respiratory failure. The reason for this variability is unclear but is in critical need of investigation. Some COVID-19 patients have been labeled with 'happy hypoxia,' in which patient complaints of dyspnoea and observable signs of respiratory distress are reported to be absent. Based on ongoing debate, we highlight key...

• Recognition of Plausible Therapeutic Agents to Combat COVID-19: An Omics Data Based Combined Approach - Coronavirus disease-2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has become an immense threat to global public health. In this study, more than 67,000 reference sequences including a complete genome sequence of SARS-CoV-2 isolate performed by us and several in silico techniques were merged to propose prospective therapeutics. Through meticulous analysis, several conserved and therapeutically suitable regions of SARS-CoV-2 such as RNA-dependent RNA...

• Understanding the immunopathogenesis of COVID-19: Its implication for therapeutic strategy - Although 80% of individuals infected with the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) recover without antiviral treatments, the other 20% progress to severe forms of pulmonary disease, suggesting that the host's immune response to the virus could influence the outcome of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects alveolar epithelial type 2 cells expressing angiotensin-converting enzyme 2, and these infected epithelial cells recruit dendritic cells, neutrophils...

From Patent Search

• Covid 19 - Chewing Gum - - link

• A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof - - link

• STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19 - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - link

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• "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. - link

• 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환의 예방 또는 치료용 조성물 - 본 발명은 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염; 및 글루카곤 수용체 작용제(glucagon receptor agonist), 위 억제 펩타이드(gastric inhibitory peptide, GIP), 글루카곤-유사 펩타이드 1(glucagon-like peptide 1, GLP-1) 및 글루카곤 수용체/위 억제 펩타이드/글루카곤-유사 펩타이드 1(Glucagon/GIP/GLP-1) 삼중 완전 작용제(glucagon receptors, gastric inhibitory peptide and glucagon-like peptide 1 (Glucagon/GIP/GLP-1) triple full agonist)로 이루어진 군으로부터 선택된 1종 이상;을 포함하는 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환 예방 또는 치료용 약학적 조성물을 제공한다. - link

• 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. - link

• SARS-CoV-2 RBD共轭纳米颗粒疫苗 - 本发明涉及免疫医学领域，具体而言，涉及一种SARS‑CoV‑2 RBD共轭纳米颗粒疫苗。该疫苗包含免疫原性复合物，所述免疫原性复合物包含：a）与SpyCatcher融合表达的载体蛋白自组装得到的纳米颗粒载体；b）与SpyTag融合表达的SARS‑CoV‑2病毒的RBD抗原；所述载体蛋白选自Ferritin、mi3和I53‑50；所述载体蛋白与所述抗原之间通过SpyCatcher‑SpyTag共价连接。 - link

• Устройство электронного контроля и дистанционного управления аппарата искусственной вентиляции легких - Полезная модель относится к медицинской технике, а именно к устройствам для воздействия на дыхательную систему пациента смесью различных газов, в частности, к устройствам для проведения искусственной вентиляции легких (ИВЛ). Технический результат предлагаемой полезной модели заключается в решении технической проблемы, состоящей в необходимости расширения арсенала технических средств, предназначенных для электронного контроля и управления ИВЛ, путем реализации возможности дистанционного управления аппаратами ИВЛ в медицинских учреждениях, не оборудованных кабельными вычислительными сетями. Указанный технический результат достигается благодаря тому, что в известное устройство электронного контроля и дистанционного управления аппарата ИВЛ, содержащее центральный микроконтроллер, а также программно-аппаратные средства управления функциями доставки воздушной смеси пациенту и многоуровневой тревожной сигнализации об отклонениях от нормативных условий и технических неполадках в аппарате ИВЛ, введены связанные друг с другом микроконтроллер связи и дистанционного управления и радиомодем, выполненный с возможностью связи с точками доступа радиканальной сети, при этом центральный микроконтроллер устройства выполнен с дополнительными входом/выходом, которые связаны с управляющими выходом/входом микроконтроллера связи и дистанционного управления, а, в зависимости от типа применяемой в медицинском учреждении радиоканальной сети связи и передачи данных, радиомодем может быть выполнен в виде интерфейсного аудиомодуля Bluetooth 4.0 BLE, приемопередающего модуля Wi-Fi либо устройства "малого радиуса действия", работающего по технологии LoRa на нелицензируемых частотах мегагерцового диапазона, например, в диапазоне 868 МГц. 3 з.п. ф-лы, 1 ил. - link