Covid-19 Sentry

Contents

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

From Preprints

• Ensemble cryo-electron microscopy reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication-transcription complex -
  The SARS-CoV-2 nonstructural proteins coordinate genome replication and gene expression. Structural analyses revealed the basis for coupling of the essential nsp13 helicase with the RNA dependent RNA polymerase (RdRp) where the holo-RdRp and RNA substrate (the replication-transcription complex, or RTC) associated with two copies of nsp13 (nsp132-RTC). One copy of nsp13 interacts with the template RNA in an opposing polarity to the RdRp and is envisaged to drive the RdRp backwards on the RNA template (backtracking), prompting questions as to how the RdRp can efficiently synthesize RNA in the presence of nsp13. Here, we use cryo-electron microscopy and molecular dynamics simulations to analyze the nsp132-RTC, revealing four distinct conformational states of the helicases. The results suggest a mechanism for the nsp132-RTC to turn backtracking on and off, using an allosteric mechanism to switch between RNA synthesis or backtracking in response to stimuli at the RdRp active site.
  🖺 Full Text HTML: Ensemble cryo-electron microscopy reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication-transcription complex
• Nebulized delivery of a broadly neutralizing SARS-CoV-2 RBD-specific nanobody prevents clinical, virological and pathological disease in a Syrian hamster model of COVID-19 -
  There remains an unmet need for globally deployable, low-cost therapeutics for the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Previously, we reported on the isolation and in vitro characterization of a potent single-domain nanobody, NIH-CoVnb-112, specific for the receptor binding domain (RBD) of SARS-CoV-2. Here, we report on the molecular basis for the observed broad in vitro neutralization capability of NIH-CoVnb-112 against variant SARS-CoV-2 pseudoviruses, including the currently dominant Delta variant. The structure of NIH-CoVnb-112 bound to SARS- CoV-2 RBD reveals a large contact surface area overlapping the angiotensin converting enzyme 2 (ACE2) binding site, which is largely unencumbered by the common RBD mutations. In an in vivo pilot study, we demonstrate effective reductions in weight loss, viral burden, and lung pathology in a Syrian hamster model of COVID-19 following nebulized delivery of NIH-CoVnb-112. These findings support the further development of NIH-CoVnb-112 as a potential adjunct preventative therapeutic for the treatment of SARS-CoV-2 infection.
  🖺 Full Text HTML: Nebulized delivery of a broadly neutralizing SARS-CoV-2 RBD-specific nanobody prevents clinical, virological and pathological disease in a Syrian hamster model of COVID-19
• Expression and novel alternative purification of the recombinant nucleocapsid (N) protein of SARS-CoV-2 in Escherichia coli for the serodiagnosis of COVID-19 -
  The SARS-CoV-2 coronavirus causes severe acute respiratory syndrome and has caused a global pandemic by causing the COVID-19 disease. To monitor and control it, diagnostic methods such as molecular and serological tests are necessary. The serological approach use SARS-CoV-2 antigens to detect the antibodies present in patients using quantitative techniques such as enzyme-linked immunosorbent assay (ELISA) or qualitative rapid tests such as lateral flow chromatography (RDT’s). The main antigens used are the spike protein (S) and the nucleocapsid protein (N). Both proteins are obtained in different expression systems, in eukaryotic cells, their production is expensive, so in this work we chose a simpler and cheaper system such as prokaryotic to express and purify the N protein. Thereore, the nucleotide sequence had to being optimized to be expressed in Escherichia coli. The protein N is sensitive to E.coli proteases and also has the ability to self-proteolyze under native conditions, degrading into different fragments. However, under denaturing conditions, using urea and at pH 5.3 it is stable and efficiently purified using metal exchange chromatography (IMAC). In our purification strategy, we surprisingly found that by not using a sonicator, a homogeneous and time-stable preparation of the recombinant antigen is obtained. An approximate yield of 200 mg / L was obtained. It was then tested with healthy sera and sera from COVID-19 convalescent patients in Wester-blot tests that were able to recognize it. Our work provides a novel strategy to produce the SARS-CoV-2 protein N so that it can be used as an input in the development and innovation of serological tests in the diagnosis of COVID-19.
  🖺 Full Text HTML: Expression and novel alternative purification of the recombinant nucleocapsid (N) protein of SARS-CoV-2 in Escherichia coli for the serodiagnosis of COVID-19
• Total virome characterizations of game animals in China reveals a spectrum of emerging viral pathogens -
  Game animals are wildlife species often traded and consumed as exotic food, and are potential reservoirs for SARS- CoV and SARS-CoV-2. We performed a meta-transcriptomic analysis of 1725 game animals, representing 16 species and five mammalian orders, sampled across China. From this we identified 71 mammalian viruses, with 45 described for the first time. Eighteen viruses were considered as potentially high risk to humans and domestic animals. Civets (Paguma larvata) carried the highest number of potentially high risk viruses. We identified the transmission of Bat coronavirus HKU8 from a bat to a civet, as well as cross-species jumps of coronaviruses from bats to hedgehogs and from birds to porcupines. We similarly identified avian Influenza A virus H9N2 in civets and Asian badgers, with the latter displaying respiratory symptoms, as well as cases of likely human-to-wildlife virus transmission. These data highlight the importance of game animals as potential drivers of disease emergence.
  🖺 Full Text HTML: Total virome characterizations of game animals in China reveals a spectrum of emerging viral pathogens
• Serum from COVID-19 patients early in the pandemic shows limited evidence of cross-neutralization against variants of concern -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a variety of clinical symptoms ranging from no or mild to severe disease. Currently, there are multiple postulated mechanisms that may push a moderate to severe disease into a critical state. Human serum contains abundant evidence of the immune status following infection. Cytokines, chemokines, and antibodies can be assayed to determine the extent to which a patient responded to a pathogen. We examined serum and plasma from a cohort of patients infected with SARS-CoV-2 early in the pandemic and compared them to negative-control sera. Cytokine and chemokine concentrations varied depending on the severity of infection, and antibody responses were significantly increased in severe cases compared to mild to moderate infections. Neutralization data revealed that patients with high titers against an early 2020 isolate had detectable but limited neutralizing antibodies against newly circulating SARS-CoV-2 variants of concern. This study highlights the potential of re-infection for recovered COVID-19 patients.
  🖺 Full Text HTML: Serum from COVID-19 patients early in the pandemic shows limited evidence of cross-neutralization against variants of concern
• Immunogenicity and adverse events of priming with inactivated whole SARS-CoV-2 vaccine (CoronaVac) followed by boosting the ChAdOx1 nCoV-19 vaccine -

  Background: Responding to SARS-CoV-2 Delta variants escaped the vaccine-induced immunity and waning immunity from the inactivated whole virus vaccine, Thailand recently proposed a heterologous inactivated whole virus vaccine (CoronaVac) viral vector vaccine (ChAdOx1 nCoV-19) prime-boost vaccine regimen(I/V). This study aims to evaluate the immunogenicity and adverse events of this regimen by comparison with homologous CoronaVac, ChAdOx1 nCoV-19, and convalescent serum. Method: Immunogenicity was evaluated by the level of IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (S1 subunit) (anti-S RBD). At 2 weeks following the second dosage, a selection of random samples was tested for plaque reduction neutralisation (PRNT) and Pseudotype-Based Microneutralization test (PVNT) against SARS-CoV-2 variants of concern (VOCs). The safety profile of heterologous CoronaVac-ChAdOx1 nCoV-19 prime-boost vaccine regimen was described by interviewing at the 1-month visit. Result: Between April to August 2021,426 participants were included in the study, with 155 obtaining CoronaVac-ChAdOx1 nCoV-19(I/V),32 obtaining homologous CoronaVac(I/I),47 obtaining homologous ChAdOx1 nCoV-19(V/V),169 with history covid-19 infection. Geometric mean titers (GMTs) of anti-S RBD level in the I/V group compare 2wks and 4 wks ( 873.9 vs 639,p=0.00114).At 4 wks, GMTs of anti-S RBD level in I/V group was 639, 95% CI 63-726,and natural infection group 177.3, 95% CI 42-221, and V/V group 211.1, 95% CI 77-152 ,and I/I group 108.2 ,95% CI 77-152 ; all p<0.001).At 2 wks, The GMTs of 50%PRNT of 19 sampling from the I/V group is 434.5, 95% CI 326-579, against wild type and 80.4, 95% CI 56-115, against alpha and 67.4, 95% CI 48-95, against delta and 19.8, 95% CI 14-30, against beta; all p<0.001. At 2 wks, The GMTs of 50%PVNT of 15 sampling from the I/V group is 597.8, 95% CI 368-970, against wild type and 163.9, 95% CI 89-301, against alpha and 157.7, 95% CI 66-378, against delta. The AEs in the I/V schedule were well tolerated and generally unremarkable. Conclusion: The I/V vaccination is a mixed regimen that induced higher immunogenicity and shall be considered for responding to Delta Variants when only inactivated whole virus vaccine and viral vector vaccine was available.

  🖺 Full Text HTML: Immunogenicity and adverse events of priming with inactivated whole SARS-CoV-2 vaccine (CoronaVac) followed by boosting the ChAdOx1 nCoV-19 vaccine
• Reports of myocarditis and pericarditis following mRNA COVID-19 vaccines: A systematic review of spontaneously reported data from the UK, Europe, and the US and of the literature -

  Objectives: To bring together spontaneously reported data from around the world to estimate the reporting rate in different countries and better understand the risk factors for myocarditis and pericarditis following exposure to COVID-19 mRNA vaccines. Design: Systematic review of the literature and systematic review of spontaneously reported data from the United Kingdom (UK), United States (US), and European Union/European Economic Area (EU/EEA). Data sources: Spontaneously reported data for COVID-19 Vaccine Pfizer/BioNTech (Comirnaty) and COVID-19 Vaccine Moderna (Spikevax) were obtained using outputs from the UK′s Yellow Card scheme (covering the period 09/12/2020 – 20/10/2021), the Vaccine Adverse Event Reporting System (VAERS; US; covering the period 23/08/2021 – 21/10/2021), and EudraVigilance (EU/EEA; covering the period 21/12/2020 – 21/10/2021). Systematic searches of PubMed and Embase literature databases were performed with a datalock point of 11 October 2021. Eligibility criteria: All publicly available spontaneous reporting data from the three regions of interest were included. Data on events labelled “Myocarditis” and “Pericarditis” were included. No restrictions on age or gender were applied. For the systematic literature review, all pharmacoepidemiological studies of observational design investigating myocarditis and pericarditis following mRNA COVID-19 vaccines identified by our search were included. No restrictions on language or date were applied. Pre-print manuscripts were included if no peer-reviewed version was available. Studies of non-observational design, case reports, and case series were excluded. Study quality was assessed using relevant Critical Appraisal Skills Programme (CASP) tools. All studies were considered of sufficient quality for inclusion. Data extraction and synthesis: One researcher extracted data from spontaneous reporting systems and published pharmacoepidemiological studies. Spontaneously reported events of myocarditis and pericarditis were presented for each individual data source, and stratified by vaccine, age, sex, and dose where this information was available. Vaccination data were obtained to the same date, and reporting rates were calculated for the events of myocarditis and pericarditis for each population of interest. For published pharmacoepidemiological studies, the study design, participant characteristics, and study results were tabulated. Results: Overall, there were 435 reports of myocarditis and 327 reports of pericarditis reported to the UK9s Yellow Card scheme up to 20 October 2021. To 21 October 2021, in the US, 1936 reports of myocarditis and 1271 reports of pericarditis had been submitted to VAERS; there had been 2924 reports of myocarditis and 1855 reports of pericarditis submitted to EudraVigilance to the same date. Most reports (73.3%) had been submitted following Comirnaty (Pfizer/BioNTech). Males represented 74.9% of reports of myocarditis and 56.9% of pericarditis overall (for US and EU/EEA populations only), and the majority of reports concerned vaccinees ages under 40 years. Reports were more frequent following the second dose of mRNA COVID-19 vaccine. Reporting rates of myocarditis and pericarditis were consistent between the data sources. Seven pharmacoepidemiological studies were included; results of these studies were largely consistent with results of our spontaneous report analyses. Conclusions: This study provides evidence that younger vaccinees more frequently report myocarditis and pericarditis following mRNA COVID-19 vaccines compared with older vaccinees. These events had mild clinical course followed by full recovery in most cases. Results from published literature supported the results of our analyses.

  🖺 Full Text HTML: Reports of myocarditis and pericarditis following mRNA COVID-19 vaccines: A systematic review of spontaneously reported data from the UK, Europe, and the US and of the literature
• “Resistance and Care in the time of COVID-19: Archaeology in 2020” -
  The COVID-19 pandemic offered humanity a portal via which we could break with the past and imagine our world anew. This article reviews how over the course of 2020, a series of intersecting crises at the nexus of racism, settler colonialism, climate change and sexual harassment have prompted acts of resistance and care in the field of archaeology. Throughout the article, we provide concrete suggestions as to how we can continue the work of movements begun over the course of the past year to improve dynamics within our field and use the lessons from our field to improve life for all people in the world and for our planet.
  🖺 Full Text HTML: “Resistance and Care in the time of COVID-19: Archaeology in 2020”
• The snoGloBe interaction predictor reveals a broad spectrum of C/D snoRNA RNA targets -
  Box C/D small nucleolar RNAs (snoRNAs) are a conserved class of RNA known for their role in guiding ribosomal RNA 2’-O-ribose methylation through base pairing with targeted sequences. Recently, C/D snoRNAs were also implicated in regulating the expression of non-ribosomal genes through different modes of binding. Large scale RNA-RNA interaction datasets detect many snoRNAs binding messenger RNA. However, these studies provide a narrow portrait of snoRNA targets forming under specific experimental conditions. To enable a more comprehensive study of C/D snoRNA interactions, we created snoGloBe, a human C/D snoRNA machine learning interaction predictor based on a gradient boosting classifier. SnoGloBe considers the target type, and position and sequence of the interactions, enabling it to outperform existing predictors. Interestingly, for specific snoRNAs, snoGloBe identifies strong enrichment of interactions near gene expression regulatory elements including splice sites. Abundance and splicing of predicted targets were altered upon the knockdown of their associated snoRNA. Strikingly, the predicted snoRNA interactions often overlap with the binding sites of functionally related RNA binding proteins, reinforcing their role in gene expression regulation. The interactions of snoRNAs are not randomly distributed but often accumulate in functionally related transcripts sharing common regulatory elements suggesting coordinated regulatory function. The wide scope of snoGloBe makes it an excellent tool for discovering viral RNA targets, which is evident from its capacity to identify snoRNAs targeting SARS-CoV-2 RNA, known to be heavily methylated. Overall, snoGloBe is capable of identifying experimentally validated binding sites and predicting novel sites with shared regulatory function.
  🖺 Full Text HTML: The snoGloBe interaction predictor reveals a broad spectrum of C/D snoRNA RNA targets
• ImputeCoVNet: 2D ResNet Autoencoder for Imputation of SARS-CoV-2 Sequences -
  We describe a new deep learning approach for the imputation of SARS-CoV-2 variants. Our model, ImputeCoVNet, consists of a 2D ResNet Autoencoder that aims at imputing missing genetic variants in SARS-CoV-2 sequences in an efficient manner. We show that ImputeCoVNet leads to accurate results at minor allele frequencies as low as 0.0001. When compared with an approach based on Hamming distance, ImputeCoVNet achieved comparable results with significantly less computation time. We also present the provision of geographical metadata (e.g., exposed country) to decoder increases the imputation accuracy. Additionally, by visualizing the embedding results of SARS-CoV-2 variants, we show that the trained encoder of ImputeCoVNet, or the embedded results from it, recapitulates viral clade’s information, which means it could be used for predictive tasks using virus sequence analysis.
  🖺 Full Text HTML: ImputeCoVNet: 2D ResNet Autoencoder for Imputation of SARS-CoV-2 Sequences
• Fine-tuning the Spike: Role of the nature and topology of the glycan shield in the structure and dynamics of SARS- CoV-2 S -
  The dense glycan shield is an essential feature of the SARS-CoV-2 spike (S) architecture, key to immune evasion and to the activation of the prefusion conformation. Recent studies indicate that the occupancy and structures of the SARS- CoV-2 S glycans depend not only on the nature of the host cell, but also on the structural stability of the trimer; a point that raises important questions about the relative competence of different glycoforms. Moreover, the functional role of the glycan shield in the SARS-CoV-2 pathogenesis suggests that the evolution of the sites of glycosylation is potentially intertwined with the evolution of the protein sequence to affect optimal activity. Our results from multi- microsecond molecular dynamics simulations indicate that the type of glycosylation at N234, N165 and N343 greatly affects the stability of the receptor binding domain (RBD) open conformation, and thus its exposure and accessibility. Furthermore, our results suggest that the loss of glycosylation at N370, a newly acquired modification in the SARS-CoV-2 S glycan shields topology, may have contributed to increase the SARS-CoV-2 infectivity as we find that N-glycosylation at N370 stabilizes the closed RBD conformation by binding a specific cleft on the RBD surface. We discuss how the absence of the N370 glycan in the SARS-CoV-2 S frees the RBD glycan binding cleft, which becomes available to bind cell- surface glycans, potentially increases host cell surface localization.
  🖺 Full Text HTML: Fine- tuning the Spike: Role of the nature and topology of the glycan shield in the structure and dynamics of SARS-CoV-2 S
• Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice -
  Drug repurposing has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against SARS-CoV-2 with relevant potency. Of the 1,942 compounds tested, 21 exhibited a substantial antiviral activity in Vero-81 cells. Among them, clofoctol, an antibacterial drug used for the treatment of bacterial respiratory tract infections, was further investigated due to favorable safety profile and pharmacokinetic properties. Notably, the peak concentration of clofoctol that can be achieved in human lungs is more than 20 times higher than its IC50 measured against SARS-CoV-2 in human pulmonary cells. This compound inhibits SARS-CoV-2 at a post-entry step. Lastly, therapeutic treatment of human ACE2 receptor transgenic mice decreased viral load, reduced inflammatory gene expression and lowered pulmonary pathology. Altogether, these data strongly support clofoctol as a therapeutic candidate for the treatment of COVID-19 patients.
  🖺 Full Text HTML: Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice
• Tenofovir Disoproxil Fumarate and severity of COVID-19 in people with HIV infection -

  Background Effective, safe, and affordable antivirals are needed for COVID-19. Tenofovir has not been studied in randomized trials despite evidence consistent with its effectiveness against COVID-19. Methods We studied HIV-positive individuals on antiretroviral therapy (ART) in 2020 at 69 HIV clinics in Spain. We collected data on sociodemographics, ART, CD4-cell count, HIV-RNA viral load, comorbidities and the following outcomes: laboratory-confirmed SARS-CoV-2 infection, COVID-19 hospitalization, intensive care unit (ICU) admission and death. We compared the 48-week risks for individuals receiving tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/ FTC, abacavir (ABC)/lamivudine (3TC), and other regimes. All estimates were adjusted for clinical and sociodemographic characteristics via inverse probability weighting. Results Of 51,558 eligible individuals, 39.6% were on TAF/FTC, 11.9% on TDF/FTC, 26.6% on ABC/3TC, 21.8% on other regimes. There were 2,402 documented SARS-CoV-2 infections (425 hospitalizations, 45 ICU admissions, 37 deaths). Compared with TAF/FTC, the estimated risk ratios (RR) (95% CI) of hospitalization were 0.66 (0.43, 0.91) for TDF/FTC and 1.29 (1.02, 1.58) for ABC/3TC, the RRs of ICU admission were 0.28 (0.11, 0.90) for TDF/FTC and 1.39 (0.70, 2.80) for ABC/3TC, and the RRs of death were 0.37 (0.23, 1.90) for TDF/FTC and 2.02 (0.88-6.12) for ABC/3TC. The corresponding RRs of hospitalization for TDF/FTC were 0.49 (0.24, 0.81) in individuals ≥50 years and 1.15 (0.59, 1.93) in younger individuals. Conclusion Our findings suggest that, compared with other antiretrovirals, TDF/FTC lowers COVID-19 severity among HIV-positive individuals with virological control. This protective effect may be restricted to individuals aged 50 years and older.

  🖺 Full Text HTML: Tenofovir Disoproxil Fumarate and severity of COVID-19 in people with HIV infection
• ANALYSIS OF IMMUNE ESCAPE VARIANTS FROM ANTIBODY-BASED THERAPEUTICS AGAINST COVID-19. -

  Accelerated SARS-CoV-2 evolution under selective pressure by massive deployment of neutralizing antibody-based therapeutics is a concern with potentially severe implications for public health. We review here reports of documented immune escape after treatment with monoclonal antibodies and COVID19 convalescent plasma (CCP). While the former is mainly associated with specific single amino acid mutations at residues within the receptor-binding domain (e.g., E484K/Q, Q493R, and S494P), the few cases of immune evasion after CCP were associated with recurrent deletions within the N-terminal domain of Spike protein (e.g, delHV69-70, delLGVY141-144 and delAL243-244). Continuous genomic monitoring of non-responders is needed to better understand immune escape frequencies and fitness of emerging variants.

• SARS-CoV-2 ORF8 encoded protein contains a histone mimic, disrupts chromatin regulation, and enhances replication -
  SARS-CoV-2 emerged in China at the end of 2019 and caused the global pandemic of COVID-19, a disease with high morbidity and mortality. While our understanding of this new virus is rapidly increasing, gaps remain in our understanding of how SARS-CoV-2 can effectively suppress host cell antiviral responses. Recent work on other viruses has demonstrated a novel mechanism through which viral proteins can mimic critical regions of human histone proteins. Histone proteins are responsible for governing genome accessibility and their precise regulation is critical for the ability of a cell to control transcription and respond to viral threats. Here, we show that the protein encoded by ORF8 (Orf8) in SARS-CoV-2 functions as a histone mimic of the ARKS motif in histone 3. Orf8 is associated with chromatin, binds to numerous histone-associated proteins, and is itself acetylated within the histone mimic site. Orf8 expression in cells disrupts multiple critical histone post-translational modifications (PTMs) including H3K9ac, H3K9me3, and H3K27me3 and promotes chromatin compaction while Orf8 lacking the histone mimic motif does not. Further, SARS-CoV-2 infection in human cell lines and postmortem patient lung tissue cause these same disruptions to chromatin. However, deletion of the Orf8 gene from SARS-CoV-2 largely blocks its ability to disrupt host-cell chromatin indicating that Orf8 is responsible for these effects. Finally, deletion of the ORF8 gene affects the host-cell transcriptional response to SARS-CoV-2 infection in multiple cell types and decreases the replication of SARS-CoV-2 in human induced pluripotent stem cell-derived lung alveolar type 2 (iAT2) pulmonary cells. These findings demonstrate a novel function for the poorly understood ORF8-encoded protein and a mechanism through which SARS-CoV-2 disrupts host cell epigenetic regulation. Finally, this work provides a molecular basis for the finding that SARS-CoV-2 lacking ORF8 is associated with decreased severity of COVID-19.
  🖺 Full Text HTML: SARS-CoV-2 ORF8 encoded protein contains a histone mimic, disrupts chromatin regulation, and enhances replication

From Clinical Trials

• BREATHE: Virtual Self-management for Long COVID-19 - Condition:   COVID-19
  Intervention:   Other: BREATHE
  Sponsor:  
  University of Calgary
  Not yet recruiting

• Adding Colchicine to Tocilizumab in Patients With Severe COVID-19 Pneumonia. - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Colchicine
  Sponsor:  
  Hamad Medical Corporation
  Recruiting

• the Safety and Efficacy of Meplazumab in Patients With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Meplazumab for Injection;   Drug: Sterile normal saline (0.9%)
  Sponsor:   Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
  Not yet recruiting

• Health Information Technology for COVID-19 Testing in Schools (SCALE-UP Counts) - Condition:   COVID-19
  Interventions:   Behavioral: Text Messaging (TM);   Behavioral: Text Messaging + Health Navigation (TM+HN)
  Sponsors:   University of Utah;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  Not yet recruiting

• Hypertonic Saline Nasal Irrigation and Gargling (HSNIG) for Suspected COVID-19 in Pakistan - Condition:   COVID-19
  Intervention:   Other: Hypertonic Saline Nasal Irrigation and Gargles (HSNIG)
  Sponsors:   The Allergy and Asthma Institute, Pakistan;   University of Edinburgh
  Recruiting

• Immunogenicity And Safety of COVID-19 Vaccine , Inactivated Co -Administration With EV71 Vaccine (Vero Cell) - Condition:   COVID-19
  Intervention:   Biological: Experimental Group
  Sponsor:  
  Sinovac Biotech Co., Ltd
  Not yet recruiting

• A Study to Evaluate Safety & Immunogenicity of SARS-CoV-2 DNA Vaccine Delivered Intramuscularly Followed by Electroporation for COVID-19 - Condition:   Covid19
  Interventions:   Biological: SARS-CoV-2 DNA Vaccine;   Biological: Matching placebo
  Sponsors:   The University of Hong Kong;   Immuno Cure 3 Limited
  Not yet recruiting

• Homeopathic Treatment of Post-acute COVID-19 Syndrome - Condition:   Post-acute Covid-19 Syndrome
  Interventions:   Drug: Homeopathic Medication;   Other: Placebo
  Sponsors:   Southwest College of Naturopathic Medicine;   Samueli Institute for Information Biology
  Recruiting

• Intranasal INNA-051 for Prevention of COVID-19 in Adults - Condition:   COVID-19 Pandemic
  Interventions:   Drug: INNA-051;   Other: Placebo
  Sponsor:   ENA Respiratory Pty Ltd
  Not yet recruiting

• Effectiveness of Interactive Voice Response for COVID-19 Vaccination Training in the Democratic Republic of the Congo - Conditions:   COVID-19 Vaccine Knowledge;   COVID-19 Vaccine Beliefs
  Interventions:  
  Behavioral: COVID-19 Vaccine IVR Training;   Behavioral: Control Condition
  Sponsors:   Stanford University;   Viamo
  Not yet recruiting

• A Clinical Trial to Evaluate the Efficacy of RUTI® to Reduce the Severity of SARS-CoV-2 Infection (COVID-19) - Condition:   COVID-19
  Interventions:   Biological: RUTI® vaccine;   Biological: Placebo
  Sponsors:   RUTI Immunotherapeutics S.L.;   Archivel Farma S.L.
  Not yet recruiting

• Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 Vaccine (IN-B009) in Healthy Adults (COVID-19) - Condition:   COVID-19
  Interventions:   Biological: IN-B009 (Low-dose);   Biological: IN-B009 (High- dose)
  Sponsor:   HK inno.N Corporation
  Recruiting

• Lot-to-lot Consistency of an Inactivated SARS-CoV-2 Vaccine Between Different Workshops in Healthy Children Aged 3-17 Years - Condition:   COVID-19
  Interventions:   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 1 of the workshop 2;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 2 of the workshop 2;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 3 of the workshop 2;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 1 of the workshop 3;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 2 of the workshop 3;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 3 of the workshop 3;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 1 of the workshop 1
  Sponsor:   Sinovac Biotech Co., Ltd
  Recruiting

• The Potential Use of Nebulized Hydroxychloroquine for the Treatment of COVID-19 - Condition:   2019 Novel Coronavirus
  Interventions:   Drug: HCQ01;   Other: standard of care (SOC) for COVID-19
  Sponsors:   Ministry of Health Jordan;   King Hussein Cancer Center;   ACDIMA Biocenter;   Amman Pharmaceutical Industries;   Sana Pharmaceutical Industry
  Not yet recruiting

• The Effect Of Music On Compliance Of Patients İn COVİD-19 Intensive Care Unit With CPAP Device - Conditions:   COVID-19;   COVID-19 Acute Respiratory Distress Syndrome
  Intervention:   Device: Listening to music with a bluetooth headset to patients receiving CPAP support
  Sponsors:   SÜMEYYE BİLGİLİ;   Ataturk University
  Recruiting

From PubMed

• Severe acquired hypertriglyceridemia following COVID-19 - Severe hypertriglyceridemia is a major risk factor for acute pancreatitis. In exceptional cases, it is caused by plasma components inhibiting lipoprotein lipase activity. This phenomenon is predominantly associated with autoimmune diseases. Here, we report a case of severe hypertriglyceridemia due to a transient reduction in lipoprotein lipase activity following an episode of COVID-19 in an otherwise healthy 45-year-old woman. The lipoprotein lipase activity of the patient was markedly reduced…

• The PI3K/Akt/mTOR pathway: a potential pharmacological target in COVID-19 - Coronavirus disease 2019 (COVID-19) has emerged as a serious threat to global health. The disregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) cell signaling pathway observed in patients with COVID-19 has attracted attention for the possible use of specific inhibitors of this pathway for the treatment of the disease. Here, we review emerging data on the involvement of the PI3K/Akt/mTOR pathway in severe acute respiratory syndrome…

• Structural screening into the recognition of a potent inhibitor against non-structural protein 16: a molecular simulation to inhibit SARS-CoV-2 infection - COVID-19 infection is caused by endemic crown infection (SARS-CoV-2) and is associated with lung damage and severe immune response. Non-Structural Proteins are the central components of coronaviral transcription and replication machinery in SARS-CoV-2 and also stimulate mRNA cap methylation to avoid the immune response. Non-Structural Protein 16 (NSP16) is one of the primary targets for the drug discovery of coronaviruses. Discovering an effective inhibitor against the NSP16 in comparison with…

• A Multifunctional Neutralizing Antibody-Conjugated Nanoparticle Inhibits and Inactivates SARS-CoV-2 - The outbreak of 2019 coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), has resulted in a global pandemic. Despite intensive research, the current treatment options show limited curative efficacies. Here the authors report a strategy incorporating neutralizing antibodies conjugated to the surface of a photothermal nanoparticle (NP) to capture and inactivate SARS-CoV-2. The NP is comprised of a semiconducting polymer core and a biocompatible…

• Allosteric inhibition of SARS-CoV-2 3CL protease by colloidal bismuth subcitrate - The SARS-CoV-2 3-chymotrypsin-like protease (3CLpro or Mpro) is a key cysteine protease for viral replication and transcription, making it an attractive target for antiviral therapies to combat the COVID-19 disease. Here, we demonstrate that bismuth drug colloidal bismuth subcitrate (CBS) is a potent inhibitor for 3CLpro in vitro and in cellulo. Rather than targeting the cysteine residue at the catalytic site, CBS binds to an allosteric site and results in dissociation of the 3CLpro dimer and…

• Discovery of SARS-CoV-2 M(pro) peptide inhibitors from modelling substrate and ligand binding - The main protease (M^(pro)) of SARS-CoV-2 is central to viral maturation and is a promising drug target, but little is known about structural aspects of how it binds to its 11 natural cleavage sites. We used biophysical and crystallographic data and an array of biomolecular simulation techniques, including automated docking, molecular dynamics (MD) and interactive MD in virtual reality, QM/MM, and linear-scaling DFT, to investigate the molecular features underlying recognition of the natural…

• Different Approaches to Confronting the Biological Epidemic; Prevention Tools with an Emphasis on COVID-19: A Systematized Study - CONCLUSION: One possible approach to control the disease is to change individual behavior and lifestyle. In addition to prevention strategies, use of masks, observance of personal hygiene principles such as regular hand washing and non- contact of contaminated hands with the face, as well as observance of public health principles such as sneezing and coughing etiquettes, safe extermination of personal protective equipment must be strictly observed. The use of the previous experiences in the…

• Antiviral and Immunomodulatory Effects of Pelargonium sidoides DC. Root Extract EPs 7630 in SARS-CoV-2-Infected Human Lung Cells - Treatment options for COVID-19 are currently limited. Drugs reducing both viral loads and SARS-CoV-2-induced inflammatory responses would be ideal candidates for COVID-19 therapeutics. Previous in vitro and clinical studies suggest that the proprietary Pelargonium sidoides DC. root extract EPs 7630 has antiviral and immunomodulatory properties, limiting symptom severity and disease duration of infections with several upper respiratory viruses. Here we assessed if EPs 7630 affects SARS-CoV-2…

• Enteric Coronavirus Infection and Treatment Modeled With an Immunocompetent Human Intestine-On-A-Chip - Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human…

• High Induction of IL-6 Secretion From hUCMSCs Optimize the Potential of hUCMSCs and TCZ as Therapy for COVID-19-Related ARDS - Biological and cellular interleukin-6 (IL-6)-related therapies have been used to treat severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure, which prompted further exploration of the role of IL-6 in human umbilical cord mesenchymal stem cell (hUCMSC) therapy. Peripheral blood mononuclear cells (PBMCs) were responders cocultured with hUCMSCs or exogenous IL-6. A PBMC suppression assay was used to analyze the anti-inflammatory effects via MTT assay. The IL-6…

• Network Meta-analysis on the Changes of Amyloid Precursor Protein Expression Following SARS-CoV-2 Infection - SARS-CoV-2 infection begins with the attachment of its spike (S) protein to angiotensin-converting enzyme-2 (ACE2) followed by complex host immune responses with cardiovascular and neurological implications. Our meta-analyses used QIAGEN Ingenuity Pathway Analysis (IPA) and Knowledge Base (QKB) to investigate how the expression of amyloid precursor protein (APP) was modulated by attachment of SARS-CoV-2 S protein in the brain microvascular endothelial cells (BMVECs) and during COVID-19 in…

• A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling - Hyperinflammation plays an important role in severe and critical COVID-19. Using inconsistent criteria, many researchers define hyperinflammation as a form of very severe inflammation with cytokine storm. Therefore, COVID-19 patients are treated with anti-inflammatory drugs. These drugs appear to be less efficacious than expected and are sometimes accompanied by serious adverse effects. SARS-CoV-2 promotes cellular ATP release. Increased levels of extracellular ATP activate the purinergic…

• Natural biflavones are potent inhibitors against SARS-CoV-2 papain-like protease - Papain-like protease (PL^(pro)) is a key enzyme encoded by SARS-CoV-2 that is essential for viral replication and immune evasion. Significant suppression of viral spread and promotion of antiviral immunity can be achieved by inhibition of PL^(pro), revealing an inspiring strategy for COVID-19 treatment. This study aimed to discover PL^(pro) inhibitors by investigating the national compound library of traditional Chinese medicines (NCLTCMs), a phytochemical library comprising over 9000…

• A natural product compound inhibits coronaviral replication in vitro by binding to the conserved Nsp9 SARS-CoV-2 protein - The Nsp9 replicase is a conserved coronaviral protein that acts as an essential accessory component of the multi-subunit viral replication/transcription complex. Nsp9 is the predominant substrate for the essential nucleotidylation activity of Nsp12. Compounds specifically interfering with this viral activity would facilitate its study. Using a native mass spectrometry-based approach to screen a natural product library for Nsp9 binders, we identified an ent-kaurane natural product, oridonin,…

• Medicines for Malaria Venture COVID Box: a source for repurposing drugs with antifungal activity against human pathogenic fungi - BACKGROUND: Treatment of mycoses is often ineffective, usually prolonged, and has some side effects. These facts highlight the importance of discovering new molecules to treat fungal infections.

From Patent Search

• Anti-SARS-CoV-2 antibodies and uses thereof I - - link

• Anti-SARS-CoV-2 antibodies and uses thereof II - - link

• 휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수물 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 약 90% 이며, 건강한 성인이면, 육각수 물은 약 62% 이며, COVID-19 환자, 사고의 부상, 17만개의 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수 물을 평소보다 많이 흡수 하면서 동반 산소부족 상태가 되며, 육각수물 보충 없이 산소 호흡기를 사용하면 심각한 후유증이 발병 할 수 있다.

육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수 물을 62% ~ 80% 이상, 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

• 휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 90% 이며, 육각수물은 약 62% 이며, COVID-19, 사고 부상, 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수물을 평소보다 많이 흡수하면서 산소부족 상태가 되며, 육각수 보충 없이 산소호흡기를 사용하면 심각한 후유증이 발병 할 수 있다 육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수물을 62% ~ 80% 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

• 用于检测新冠病毒的配对抗体及其应用 - 本发明涉及一种用于检测新冠病毒的配对抗体及其应用，其包括第一检测抗体和第二检测抗体；第一检测抗体具有如SEQ ID NO:1~3所示的轻链互补决定区，以及如SEQ ID NO:4~6所示的重链互补决定区，第二检测抗体具有如SEQ ID NO:7~9所示的轻链互补决定区，以及如SEQ ID NO:10~12所示的重链互补决定区。本发明筛选得到具有上述互补决定区序列的配对抗体，其识别N蛋白的不同表位，且由于两种抗体识别的是N蛋白非核酸结合区域，不会受核酸负电荷干扰，对核酸抗原表现出了兼容性，具有较好的稳定性，同时上述配对抗体具有较高的亲和力，病毒N蛋白检测灵敏度高。 - link

• 抗KL-6双特异性抗体及基因、重组载体、药物、试剂盒 - 本发明公开了抗KL‑6双特异性抗体或其变体、或其功能性片段，所述抗KL‑6双特异性抗体或其变体、或其功能性片段包括抗PTS域和抗SEA域，所述抗PTS域的重链可变区的CDR1、CDR2和CDR3分别具有SEQ ID NO.1~3所示的氨基酸序列。本发明还提供了基因、重组载体、药物、试剂盒。本发明的抗KL‑6双特异性抗体或其变体、或其功能性片段用于与KL‑6蛋白特异性结合，基因、重组载体用于抗KL‑6双特异性抗体的制备，药物用于治疗KL‑6蛋白引起的相关疾病，试剂盒用于KL‑6蛋白的定量检测。 - link

• 基于决策树模型与逻辑回归模型组合的感染筛查方法 - 本发明公开了一种基于决策树模型与逻辑回归模型组合的感染筛查方法，其检测操作方便，可提高感染筛查准确性，该方法基于生命体征监护仪实现，生命体征监护仪与远程数据服务平台通信连接，远程数据服务平台依据临床数据进行感染筛查，该方法包括：通过生命体征监护仪检测获取用户临床数据，将临床数据随机划分为训练集、测试集，将训练集均分为两份：训练集A、训练集B，基于训练集A构建决策树模型，同时，对训练集A进行特征选择，将关键特征向量作为已构建的决策树模型的输入，获取新构造特征向量，基于组合特征向量，构造逻辑回归模型，基于决策树模型和逻辑回归模型组合，对测试集进行预测分类，获取分类结果。 - link

• 病毒中和抗体与非中和抗体联合检测方法、检测卡及应用 - 一种病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用，通过病毒受体结合蛋白夹心法原理检测中和抗体，其为通过提前设置病毒受体结合蛋白和能阻断中和抗体与其结合的作为配体的蛋白所形成的复合物，将靶向受体蛋白的非中和抗体提前捕获，保证后续通过夹心法检测中和抗体的特异性。解决了现有技术中中和抗体检测灵敏度低、特异性差以及不能区分中和抗体与非中和抗体的问题，提供了一种简便、快速、灵敏度高、特异性高的病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用。 - link

• 扩增△500-532的SARS-CoV-2 Nsp1基因的引物对及其检测方法 - 本发明公开了一种扩增Δ500‑532的SARS‑CoV‑2 Nsp1基因的引物对及其检测方法。引物对的具体序列如SEQ ID NO.1和SEQ ID NO.2所示，其检测方法为：采用引物对对SARS‑CoV‑2 Nsp1基因进行PCR，对PCR产物进行变性退火后，加入T7EI内切酶孵育，再进行PCR扩增，并判断是否存在Δ500‑532的SARS‑CoV‑2 Nsp1基因。本发明可简便快捷的区分出SARS‑CoV‑2 Nsp1基因突变型和野生型。 - link

• 多肽及其在新型冠状病毒检测中的应用 - 本发明涉及生物医学领域，具体而言，涉及一种多肽及其在新型冠状病毒检测中的应用。所述多肽包括如下部分：S——Linker——N——avi‑tag。通过经过优化的刚性linker序列把S蛋白和N蛋白串联起来，使得这两个蛋白即具备相对独立的空间构象，又增加了许多优势表位，很大程度上提高了灵敏度和信号值；此外，融合蛋白引入Avi‑tag，使得重组蛋白可以通过固定的位点被固相化，降低包被过程所带来的空间位阻的影响。由此，该多肽能够达到很高的灵敏度和特异性，并且不易发生漏检。 - link