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188 lines
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<title>12 December, 2020</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Chest CT versus RT-PCR for the Detection of COVID-19: Systematic Review and Meta-analysis of Comparative Studies</strong> -
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Objectives To compare the performance of chest computed tomography (CT) scan versus reverse transcription polymerase chain reaction (RT-PCR) as the reference standard in the initial diagnostic assessment of coronavirus disease 2019 (COVID-19) patients. Design A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A search of electronic information was conducted using the following databases: MEDLINE, EMBASE, EMCARE, CINAHL and the Cochrane Central Register of Controlled Trials (CENTRAL). Setting Studies that compared the diagnostic performance within the same patient cohort of chest CT scan versus RT-PCR in COVID-19 suspected patients. Participants Thirteen non-randomised studies enrolling 4092 patients were identified. Main Outcome Measures Sensitivity, specificity and accuracy were primary outcome measures. Secondary outcomes included other test performance characteristics and discrepant findings between both investigations. Results Chest CT had a sensitivity, specificity and accuracy of 0.91 (0.82-0.98), 0.775 (0.25-1.00) and 0.87 (0.68-0.99), respectively, with RT-PCR as the reference. Importantly, early small, China-based studies tended to favour chest CT versus later larger, non-China studies. Conclusions A relatively high false positive rate can be expected with chest CT. It may still be useful, however, in patients with a suspicious clinical presentation of COVID-19 and a negative initial SARS-CoV-2 RT-PCR. In acute cardiorespiratory presentations, negative CT scan and RT-PCR tests is likely to be reassuring.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.06.22.20136846v4" target="_blank">Chest CT versus RT-PCR for the Detection of COVID-19: Systematic Review and Meta-analysis of Comparative Studies</a>
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</div></li>
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<li><strong>Diverse Functional Autoantibodies in Patients with COVID-19</strong> -
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COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses. While pathological innate immune activation is well documented in severe disease, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the “exoproteome”). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.10.20247205v2" target="_blank">Diverse Functional Autoantibodies in Patients with COVID-19</a>
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<li><strong>Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data.</strong> -
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BACKGROUND: A recent trial (NCT04308668) found that post-exposure prophylaxis with hydroxychloroquine (HCQ) was associated with a reduced incidence of Covid-19 by 17% overall; 36% in younger subjects, 31% in household contacts and 49% given within one day. To understand these trends, we re-analyzed the released dataset. METHODS: Our protocol conformed to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). We compared the incidence of Covid-19 after HCQ or placebo, stratifying by intervention lag, age, and gender. RESULTS: Requesting additional data, we found that 52% of subjects received medication 1-2 days after the intended overnight delivery; 19% of them outside the intended four-day intervention lag. After re-analysis, there was a reduced incidence of Covid-19 associated with HCQ compared with placebo (9.6% vs. 16.5%) when received Early (up to 3 days) after exposure (RR 0.58, 95%CI 0.35 - 0.97; p=0.044; NNT 14.5) but not Late (RR 1.22, 95%CI 0.72 - 2.04). We found a significant HCQ-associated Covid-19 reduction in subjects 18 to 45 years old with Early (RR 0.54, 95%CI 0.29-0.97; p=0.0448, NNT 11.5) but not Late (RR 1.02, 95%CI 0.55-1.89) prophylaxis, attenuated in older subjects (RR 0.75, 95%CI 0-27-2.05) and by co-morbidities. There were reductions associated with Early prophylaxis in household contacts (RR 0.35, 95%CI 0.13-0.89; p=0.025, NNT 5.7) and Health Care Workers (RR 0.74, 95%CI 0.4-1.38). We did not detect effects of gender, folate, zinc, or ascorbic acid. CONCLUSIONS: Using novel data with a prospective post hoc re-analysis, hydroxychloroquine, in an age-dependent manner, was associated with reduced illness compatible with Covid-19 or confirmed infection when supplied for post-exposure prophylaxis between 1 and 3 days after high-risk or moderate-risk exposure, at higher loading and maintenance doses than in similar studies. This finding warrants prospective confirmation. Registered with the Open Science Framework (last revised September 27, 2020, osf.io/fqtnw). Plain Language Summary A recent clinical trial examined the ability of hydroxychloroquine (HCQ) to prevent Covid-19 just after an exposure to a person confirmed to have Covid-19. There was an HCQ-associated reduction of Covid-19 by an overall 17%; 36% in younger subjects, and 49% in subjects given HCQ within one day of being exposed. Likely because the study had too few patients to find what may have been a medically and economically meaningful, reduction, this effect was not statistically significant. Studying the trial data, we discovered an unintended and variable delay in the delivery of study drug which may have masked any drug effect. The investigators provided further information at our request that confirmed our theory. About half of the participants received drugs one or two days later than intended, about a fifth beyond the four days the investigators thought the drug might work. When we factored in this new information, we found that if HCQ was given early (up to three days after exposure), it was associated with a statistically significant 42% reduction of Covid-19. Giving HCQ later had no effect. There was a greater effect in younger (less than 45 years) rather than older subjects (47% vs. 25%). Gender did not seem to affect the results, but there was a greater HCQ-associated reduction (65%) when it was given early to people exposed to Covid-19 in a household environment rather than to health care workers (26%). The effects associated with HCQ were better in people without co-existing conditions. These re-calculations are important because the study, as originally analyzed, was the only randomized study that dealt with preventing Covid-19 cited by FDA to support a key public health decision made in June 2020 regarding HCQ. Although other studies have shown that the drug is not effective to treat established cases of Covid-19, our research suggests that that it is effective for prevention. Other prevention studies have failed to show a benefit of HCQ, possibly because they have used lower doses or have estimated the timing of dosing differently. Our research paves the way for our result to be confirmed under clinical trial conditions and for a re-examination of public health policy regarding this drug. Even with the introduction of vaccination, there remains a need for approaches like this to prevent Covid-19 while individual and community immunity develops, especially in subjects given a lower priority for vaccination. Short Summary A prospective re-analysis of a public dataset integrated with novel data found an HCQ-associated reduction of illness compatible with Covid-19 when received between 1 and 3 days after a high-risk or moderate-risk exposure (RR 0.58, 95% CI 0.35-0.97, p=0.044, NNT14.5).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.29.20235218v2" target="_blank">Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data.</a>
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<li><strong>A network modelling approach to assess non-pharmaceutical disease controls in a worker population: An application to SARS-CoV-2</strong> -
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<b>Background:</b> As part of a concerted pandemic response to protect public health, businesses can enact non-pharmaceutical controls to minimise exposure to pathogens in workplaces and premises open to the public. Amendments to working practices can lead to the amount, duration and/or proximity of interactions being changed, ultimately altering the dynamics of disease spread. These modifications could be specific to the type of business being operated. <b>Methods:</b> We use a data-driven approach to parameterise an individual-based network model for transmission of SARS-CoV-2 amongst the working population, stratified into work sectors. The network is comprised of layered contacts to consider risk of spread in multiple encounter settings (workplaces, households, social and other). We analyse several interventions targeted towards working practices: mandating a fraction of the population to work from home, using temporally asynchronous work patterns and introducing measures to create `COVID-secure9 workplaces. We also assess the general role of adherence to (or effectiveness of) isolation and test and trace measures and demonstrate the impact of all these interventions across a variety of relevant metrics. <b>Results:</b> The progress of the epidemic can be significantly hindered by instructing a significant proportion of the workforce to work from home. Furthermore, if required to be present at the workplace, asynchronous work patterns can help to reduce infections when compared with scenarios where all workers work on the same days, particularly for longer working weeks. When assessing COVID-secure workplace measures, we found that smaller work teams and a greater reduction in transmission risk led to a flatter temporal profile for both infections and the number of people isolating, and reduced the probability of large, long outbreaks. Finally, following isolation guidance and engaging with contact tracing alone is an effective tool to curb transmission, but is highly sensitive to adherence levels. <b>Conclusions:</b> In the absence of sufficient adherence to non-pharmaceutical interventions, our results indicate a high likelihood of SARS-CoV-2 spreading widely throughout a worker population. Given the heterogeneity of demographic attributes across worker roles, in addition to the individual nature of controls such as contact tracing, we demonstrate the utility of a network model approach to investigate workplace-targeted intervention strategies and the role of test, trace and isolation in tackling disease spread.
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</p>
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</div>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.18.20230649v5" target="_blank">A network modelling approach to assess non-pharmaceutical disease controls in a worker population: An application to SARS-CoV-2</a>
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<li><strong>Filtration Efficiency, Breathability, and Reusability of Improvised Materials for Face Masks</strong> -
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There is paucity of data on the performance of different improvised materials to cope with the COVID-19 pandemic. The goal of this study is to evaluate the filtration efficiency and breathability of improvised filtration and commonly available mask materials, as well as to assess their reusability. Materials readily available to the general public such as cotton, fragrance and additive-free dry baby cleaning wipes, and those abundantly available in the hospital setting, such as sterilization wraps, were chosen for testing, amongst others. In the COVID-important 2–5 m particle range, two-layers of cotton provided filtration efficiency between 34%–66%. Amongst potential filter materials, 300-weight sterilization wraps provided approximately 80% filtration efficiency and are readily available in the healthcare setting. The addition of sterilization wrap to cotton fabrics brought the filtration efficiency to above that of the sterilization wrap (80%-90%) at the expense of added pressure drop. Four-layers of dry baby wipes performed very well with a filtration efficiency of 85% and a reasonable pressure drop (1/3 of procedure mask). Since the material is advertised as pure spunlace polypropylene and designed to contact the skin during cleaning, it would appear generally safe as a filter insert. Of improvised filters, polypropylene electrostatic HVAC filters performed the best with filtration efficiencies of >99%, but are not recommended due to the risk of confusion with glass-based HVAC filters and uncertainty regarding trace materials used in the filter. The filtration efficiency of two-layers of cotton fabrics with one-layer of sterilization wrap slightly improved over 10 laundry cycles, while the performance of other non-wovens, like dry baby wipes, degraded more rapidly and should be considered disposable. In summary, we found that a two-layer cotton fabric can provide a comfortable, breathable and reusable option. The addition of a sterilization wrap or four-layers of pure spunlace fragrance free dry baby wipes can significantly improve filtration and block expiratory aerosols at the expense of an added pressure drop.
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</div>
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🖺 Full Text HTML: <a href="https://engrxiv.org/nrtgb/" target="_blank">Filtration Efficiency, Breathability, and Reusability of Improvised Materials for Face Masks</a>
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<li><strong>Identification of eight SARS-CoV-2 ORF7a deletion variants in 2,726 clinical specimens</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF7a, the ortholog of SARS-CoV ORF7a, is a type I transmembrane protein and plays an important role in virus-host interactions. Deletion variants in ORF7a may influence virulence, but only a few such isolates have been reported. Here, we report 8 unique ORF7a deletion variants of 6 to 96 nucleotides in length identified from 2,726 clinical specimens collected in March of 2020.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.10.418855v1" target="_blank">Identification of eight SARS-CoV-2 ORF7a deletion variants in 2,726 clinical specimens</a>
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<li><strong>A traditional Chinese medicine, Respiratory Detox Shot (RDS), inhibits the infection of SARS-CoV, SARS-CoV-2, and the Influenza A virus in vitro</strong> -
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<div>
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The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has resulted in the infection of over 60 million people and has caused over 1.4 million deaths as of December 2020 in more than 220 countries and territories. Currently, there is no effective treatment for COVID-19 to reduce mortality. We investigated the potential anti-coronavirus activities of an oral liquid traditional Chinese medicine (TCM), Respiratory Detox Shot (RDS), which contains herbal ingredients traditionally used in China to manage lung diseases. Here we report that RDS inhibited the infection of target cells by SARS-CoV and SARS-CoV-2 pseudoviruses, and by infectious wild-type SARS-CoV-2. We further demonstrated that RDS inhibits viral early infection steps. In addition, we found that RDS can also block the infection of target cells by Influenza A virus. These results suggest that RDS may broadly inhibit the infection of respiratory viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.10.420489v1" target="_blank">A traditional Chinese medicine, Respiratory Detox Shot (RDS), inhibits the infection of SARS-CoV, SARS-CoV-2, and the Influenza A virus in vitro</a>
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<li><strong>Profound Treg perturbations correlate with COVID-19 severity</strong> -
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The hallmark of severe COVID-19 disease has been an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We explored the hypothesis that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in both Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, which correlated with poor outcomes. Accordingly, these Tregs over-expressed a range of suppressive effectors, but also pro-inflammatory molecules like IL32. Most strikingly, they acquired similarity to tumor-infiltrating Tregs, known to suppress local anti-tumor responses. These traits were most marked in acute patients with severe disease, but persisted somewhat in convalescent patients. These results suggest that Tregs may play nefarious roles in COVID-19, via suppressing anti-viral T cell responses during the severe phase of the disease, and/or via a direct pro-inflammatory role.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.11.416180v1" target="_blank">Profound Treg perturbations correlate with COVID-19 severity</a>
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<li><strong>BNT162b vaccines are immunogenic and protect non-human primates against SARS-CoV-2</strong> -
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A safe and effective vaccine against COVID-19 is urgently needed in quantities sufficient to immunise large populations. We report the preclinical development of two BNT162b vaccine candidates, which contain lipid-nanoparticle (LNP) formulated nucleoside-modified mRNA encoding SARS-CoV-2 spike glycoprotein-derived immunogens. BNT162b1 encodes a soluble, secreted, trimerised receptor-binding domain (RBD-foldon). BNT162b2 encodes the full-length transmembrane spike glycoprotein, locked in its prefusion conformation (P2 S). The flexibly tethered RBDs of the RBD-foldon bind ACE2 with high avidity. Approximately 20 percent of the P 2S trimers are in the two-RBD “down”, one-RBD “up” state. In mice, one intramuscular dose of either candidate elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong TH1 CD4+ and IFNy+ CD8+ T-cell responses. Prime/boost vaccination of rhesus macaques with BNT162b candidates elicits SARS-CoV-2 neutralising geometric mean titres 8.2 to 18.2 times that of a SARS-CoV-2 convalescent human serum panel. The vaccine candidates protect macaques from SARS-CoV-2 challenge, with BNT162b2 protecting the lower respiratory tract from the presence of viral RNA and with no evidence of disease enhancement. Both candidates are being evaluated in phase 1 trials in Germany and the United States. BNT162b2 is being evaluated in an ongoing global, pivotal Phase 2/3 trial (NCT04380701, NCT04368728).
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.11.421008v1" target="_blank">BNT162b vaccines are immunogenic and protect non-human primates against SARS-CoV-2</a>
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<li><strong>High-throughput, low-cost and rapid DNA sequencing using surface-coating techniques</strong> -
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The speed, expense and throughput of genomic sequencing impose limitations on its use for time-sensitive acute cases, such as rare or antibiotic resistant infections, and large-scale testing that is necessary for containing COVID-19 outbreaks using source-tracing. The major bottleneck for increasing the bandwidth and decreasing operating costs of next-generation sequencers (NGS) is the flow cell that supplies reagents for the biochemical processes; this subsystem has not significantly improved since 2005. Here we report a new method for sourcing reagents based on surface coating technology (SCT): the DNA adhered onto the biochip is directly contacted by a reagent-coated polymeric strip. Compared with flow cells the reagent layers are an order of magnitude thinner while both the reagent exchange rate and biochip area are orders of magnitude greater. These improvements drop the turn-around time from days to twelve hours and the cost for whole genome sequencing (WGS) from about $1000 to $15, as well as increase data production by several orders of magnitude. This makes NGS more affordable than many blood tests while rapidly providing detailed genomic information about microbial and viral pathogens, cancers and genetic disorders for targeted treatments and personalized medicine. This data can be pooled in population-wide databases for accelerated research and development as well providing detailed real-time data for tracking and containing outbreaks, such as the current COVID-pandemic.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.10.418962v1" target="_blank">High-throughput, low-cost and rapid DNA sequencing using surface-coating techniques</a>
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<li><strong>Duplex formation between the template and the nascent strand in the transcription-regulating sequences determines the site of template switching in SARS - CoV-2</strong> -
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Recently published transcriptomic data of the SARS-CoV-2 coronavirus show that there is a large variation in the frequency and steady state levels of subgenomic mRNA sequences. This variation is derived from discontinuous subgenomic RNA synthesis where the polymerase switches template from a 3’ proximal genome body sequence to a 5’ untranslated leader sequence. This leads to a fusion between the common 5’ leader sequence and a 3’ proximal body sequence in the RNA product. This process revolves around a common core sequence (CS) that is present at both the template sites that make up the fusion junction. Base-pairing between the leader CS and the nascent complementary minus strand body CS, and flanking regions (together called the transcription regulating sequence, TRS) is vital for this template switching event. However, various factors can influence the site of template switching within the same TRS duplex. Here, we model the duplexes formed between the leader and complementary body TRS regions, hypothesising the role of the stability of the TRS duplex in determining the major sites of template switching for the most abundant mRNAs. We indicate that the stability of secondary structures and the speed of transcription play key roles in determining the probability of template switching in the production of subgenomic RNAs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.11.416818v1" target="_blank">Duplex formation between the template and the nascent strand in the transcription-regulating sequences determines the site of template switching in SARS - CoV-2</a>
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<li><strong>Conformational Ensembles of Non-Coding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations</strong> -
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The 5’ untranslated region (UTR) of SARS-CoV-2 genome is a conserved, functional and structured genomic region consisting of several RNA stem-loop elements. While the secondary structure of such elements has been determined experimentally, their three-dimensional structure is not known yet. Here, we predict structure and dynamics of five RNA stem-loops in the 5’-UTR of SARS-CoV-2 by extensive atomistic molecular dynamics simulations, more than 0.5ms of aggregate simulation time, in combination with enhanced sampling techniques. We compare simulations with available experimental data, describe the resulting conformational ensembles, and identify the presence of specific structural rearrengements in apical and internal loops that may be functionally relevant. Our atomic-detailed structural predictions reveal a rich dynamics in these RNA molecules, could help the experimental characterisation of these systems, and provide putative three-dimensional models for structure-based drug design studies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.11.421784v1" target="_blank">Conformational Ensembles of Non-Coding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations</a>
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<li><strong>EVs analysis in the COVID-19 era: insights on serum inactivation protocols towards downstream isolation and analysis</strong> -
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Since the outbreak of COVID-19 crisis, the handling of biological samples from known or suspected SARS-CoV-2 positive individuals demanded the use of inactivation protocols aimed at ensuring laboratory operators safety. While not standardized, these practices can be roughly divided in two categories, namely heat inactivation and solvent-detergent treatments. As such, these routine procedures should also apply to samples intended for Extracellular Vesicles (EVs) analysis. Assessing the impact of virus inactivating pre-treatments is therefore of pivotal importance, given the well-known variability introduced by different pre-analytical steps on downstream EVs isolation and analysis. Common guidelines on inactivation protocols tailored to best address EVs-specific requirements will be likely needed among the EVs community, yet deep investigations in this direction have not been reported so far. In the attempt of sparking interest on this highly relevant topic, we here provide preliminary insights on SARS-CoV-2 inactivation practices to be adopted prior serum EVs analysis by comparing solvent/detergent treatment vs. heat inactivation. Our analysis entailed the evaluation of EVs recovery and purity along with biochemical and biophysical profiling by means of Nanoparticle Tracking Analysis, Western Blotting, Atomic Force Microscopy, Transmission Electron Microscopy, miRNA content (digital droplet PCR) and tetraspanin assessment by antibody microarrays. Our data suggest an increase in UC recovery following heat-treatment, however accompanied by a marked enrichment in EVs-associated contaminants. On the contrary, solvent/detergent treatment is promising for small EVs (< 150nm range), yet a depletion of larger vesicular entities was detected. This work represents a first step towards the identification of optimal bio-samples inactivation protocols targeted to EVs analysis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.10.417758v1" target="_blank">EVs analysis in the COVID-19 era: insights on serum inactivation protocols towards downstream isolation and analysis</a>
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<li><strong>Why the SARS-CoV-2 antibody test results may be misleading: insights from a longitudinal analysis of COVID-19</strong> -
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To estimate the effectiveness of vaccines in development, a robust mechanism is required to understand immunity, risks of reinfection and measure the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and how this may change over time. This study is a longitudinal analysis of COVID-19 infection rates using PCR, membrane immunoassay and chemiluminescent microparticle immunoassay (CMIA) diagnostic tests. Our data confirm that antibody levels wane in the three months after symptom onset. Comparison of the three methods used suggests that quantitative CMIA testing may exaggerate numbers of COVID-19 negative individuals.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.08.20245894v2" target="_blank">Why the SARS-CoV-2 antibody test results may be misleading: insights from a longitudinal analysis of COVID-19</a>
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<li><strong>IGI-LuNER: single-well multiplexed RT-qPCR test for SARS-CoV-2</strong> -
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Commonly used RT-qPCR-based SARS-CoV-2 diagnostics require 2-3 separate reactions or rely on detection of a single viral target, adding time and cost or risk of false-negative results. Currently, no test combines detection of widely used SARS-CoV-2 E- and N-gene targets and a sample control in a single, multiplexed reaction. We developed the IGI-LuNER RT-qPCR assay using the Luna Probe Universal One-Step RT-qPCR master mix with publicly available primers and probes to detect SARS-CoV-2 N gene, E gene, and human RNase P (NER). This combined, cost-effective test can be performed in 384-well plates with detection sensitivity suitable for clinical reporting, and will aid in future sample pooling efforts, thus improving throughput of SARS-CoV-2 detection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.10.20247338v1" target="_blank">IGI-LuNER: single-well multiplexed RT-qPCR test for SARS-CoV-2</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating Safety, Pharmacokinetics and Clinical Benefit of Silmitasertib (CX-4945) in Subjects With Moderate COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Silmitasertib; Drug: SOC<br/><b>Sponsor</b>: Chris Recknor, MD<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Convalescent Plasma for Treatment of COVID-19: An Open Randomised Controlled Trial</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: SARS-CoV-2 convalescent plasma; Other: Standard of care<br/><b>Sponsors</b>: Joakim Dillner; Karolinska Institutet; Danderyd Hospital; Falu Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase II / III Study of COVID-19 DNA Vaccine (AG0302-COVID19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Group A (AG0302-COVID19); Biological: Group A (Placebo); Biological: Group B (AG0302-COVID19); Biological: Group B (Placebo)<br/><b>Sponsors</b>: AnGes, Inc.; Japan Agency for Medical Research and Development<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Use of BCG Vaccine as a Preventive Measure for COVID-19 in Health Care Workers</strong> - <b>Condition</b>: COVID 19 Vaccine<br/><b>Intervention</b>: Biological: BCG vaccine<br/><b>Sponsors</b>: Universidade Federal do Rio de Janeiro; Ministry of Science and Technology, Brazil<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>At-Home Infusion Using Bamlanivimab in Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: bamlanivimab<br/><b>Sponsors</b>: Daniel Griffin, MD PhD; Eli Lilly and Company; Optum, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of High-dose Vitamin C Combined With Chinese Medicine Against Coronavirus Pneumonia (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C; Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose; Drug: Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment<br/><b>Sponsor</b>: Xi’an International Medical Center Hospital<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IFN-beta 1b and Remdesivir for COVID19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Interferon beta-1b; Drug: Remdesivir<br/><b>Sponsor</b>: The University of Hong Kong<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 And Geko Evaluation: The CAGE Study</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Device: geko T3<br/><b>Sponsor</b>: Lawson Health Research Institute<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Biological: AT-100<br/><b>Sponsor</b>: Airway Therapeutics, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>LYT-100 in Post-acute COVID-19 Respiratory Disease</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: LYT-100; Other: Placebo<br/><b>Sponsors</b>: PureTech; Clinipace Worldwide; Novotech (Australia) Pty Limited<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Resolving Inflammatory Storm in COVID-19 Patients by Omega-3 Polyunsaturated Fatty Acids -</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Omegaven®; Drug: Sodium chloride<br/><b>Sponsor</b>: Karolinska University Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>WHO COVID-19 Solidarity Trial for COVID-19 Treatments</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Remdesivir; Drug: Acalabrutinib; Drug: Interferon beta-1a; Other: Standard of Care<br/><b>Sponsor</b>: The University of The West Indies<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Thrombosis Prevention Trials: Post-hospital Thromboprophylaxis</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Apixaban 2.5 MG; Drug: Placebo<br/><b>Sponsors</b>: Thomas Ortel, M.D., Ph.D.; National Heart, Lung, and Blood Institute (NHLBI)<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Urine Alkalinisation to Prevent AKI in COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: Sodium Bicarbonate 150Meq/L/D5W Inj<br/><b>Sponsor</b>: Guy’s and St Thomas’ NHS Foundation Trust<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Outpatient Pragmatic Platform Study (COPPS) - Master Protocol</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Acebilustat; Drug: Camostat<br/><b>Sponsor</b>: Stanford University<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Candidate Binding Sites for Allosteric Inhibition of the SARS-CoV-2 Main Protease from the Analysis of Large-Scale Molecular Dynamics Simulations</strong> - We analyzed a 100 μs MD trajectory of the SARS-CoV-2 main protease by a non-parametric data analysis approach which allows characterizing a free energy landscape as a simultaneous function of hundreds of variables. We identified several conformations that, when visited by the dynamics, are stable for several hundred nanoseconds. We explicitly characterize and describe these metastable states. In some of these configurations, the catalytic dyad is less accessible. Stabilizing them by a suitable…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Coronavirus disease 2019 (COVID-19), human erythrocytes and the PKC-alpha/-beta inhibitor chelerythrine -possible therapeutic implication</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. Until now, diverse drugs have been used for the treatment of COVID-19. These drugs are associated with severe side effects, e.g. induction of erythrocyte death, named eryptosis. This massively affects the oxygen (O(2)) supply of the organism. Therefore, three elementary aspects should be considered simultaneously: (1) a potential drug should directly attack the virus, (2) eliminate virus-infected host cells and (3)…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>First Report of Tocilizumab Use in a Cohort of Latin American Patients Hospitalized for Severe COVID-19 Pneumonia</strong> - Introduction/objectives: An interleukin-6 inhibition strategy could be effective in selected COVID-19 patients. The objective is to present our experience of tocilizumab use in patients with severe COVID-19. Methods: Observational retrospective cohort study. Hospitalized patients were evaluated by our multidisciplinary team for eventual use of tocilizumab. Patients with progressive ventilatory impairment and evidence of a hyperinflammatory state despite usual treatment received tocilizumab 8…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Repurposing Known Drugs as Covalent and Non-covalent Inhibitors of the SARS-CoV-2 Papain-Like Protease</strong> - In the absence of an approved vaccine, developing effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antivirals is essential to tackle the current pandemic health crisis due to the coronavirus disease 2019 (COVID-19) spread. As any traditional drug discovery program is a time-consuming and costly process requiring more than one decade to be completed, in silico repurposing of existing drugs is the preferred way for rapidly selecting promising clinical candidates. We present a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Proton pump inhibitors and the risk of severe COVID-19: a post-hoc analysis from the Korean nationwide cohort</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Silybin B and Cianidanol Inhibit M pro and Spike Protein of SARS-CoV-2: Evidence from in Silico Molecular Docking Studies</strong> - CONCLUSION: Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural Products Homoharringtonine and Emetine Alkaloids for SARSCoV-2 Treatment Options</strong> - CONCLUSION: This review specifically focuses on the recent findings of these alkaloids against coronaviruses and possible treatment options for SARS-CoV-2. It is expected that natural products as alkaloids from herbal plants could be considered as novel and valuable candidates for the new antiviral drugs against SARS-CoV-2.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Protease-activated receptor 1 as a potential therapeutic target for COVID-19</strong> - Acute respiratory disease caused by a novel coronavirus (SARS-CoV-2) has spread all over the world, since its discovery in 2019, Wuhan, China. This disease is called COVID-19 and already killed over 1 million people worldwide. The clinical symptoms include fever, dry cough, dyspnea, headache, dizziness, generalized weakness, vomiting, and diarrhea. Unfortunately, so far, there is no validated vaccine, and its management consists mainly of supportive care. Venous thrombosis and pulmonary embolism…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of SARS-CoV-2 Entry into Host Cells Using Small Molecules</strong> - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a virus belonging to the Coronavirus family, is now known to cause Coronavirus Disease (Covid-19) which was first recognized in December 2019. Covid-19 leads to respiratory illnesses ranging from mild infections to pneumonia and lung failure. Strikingly, within a few months of its first report, Covid-19 has spread worldwide at an exceptionally high speed and it has caused enormous human casualties. As yet, there is no specific…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Topoisomerase 1 inhibition therapy protects against SARS-CoV-2-induced inflammation and death in animal models</strong> - The ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro and in vivo analyses, we report that Topoisomerase 1 (Top1) inhibition suppresses lethal inflammation…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures</strong> - The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, has rendered our understanding of coronavirus biology more essential than ever. Small molecule chemical probes offer to both reveal novel aspects of virus replication and to serve as leads for antiviral therapeutic development. The RNA-biased amiloride scaffold was recently tuned to target a viral RNA structure critical for translation in enterovirus 71, ultimately uncovering a novel mechanism to modulate positive-sense…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ca (2+) -dependent mechanism of membrane insertion and destabilization by the SARS-CoV-2 fusion peptide</strong> - Cell penetration after recognition of the SARS-CoV-2 virus by the ACE2 receptor, and the fusion of its viral envelope membrane with cellular membranes, are the early steps of infectivity. A region of the Spike protein (S) of the virus, identified as the “fusion peptide” (FP), is liberated at its N-terminal site by a specific cleavage occurring in concert with the interaction of the receptor binding domain of the Spike. Studies have shown that penetration is enhanced by the required binding of Ca…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Repurposing the Ebola and Marburg Virus Inhibitors Tilorone, Quinacrine and Pyronaridine: In vitro Activity Against SARS-CoV-2 and Potential Mechanisms</strong> - SARS-CoV-2 is a newly identified virus that has resulted in over 1.3 M deaths globally and over 59 M cases globally to date. Small molecule inhibitors that reverse disease severity have proven difficult to discover. One of the key approaches that has been widely applied in an effort to speed up the translation of drugs is drug repurposing. A few drugs have shown in vitro activity against Ebola virus and demonstrated activity against SARS-CoV-2 in vivo . Most notably the RNA polymerase targeting…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A proposed molecular mechanism for pathogenesis of severe RNA-viral pulmonary infections</strong> - Background: Certain riboviruses can cause severe pulmonary complications leading to death in some infected patients. We propose that DNA damage induced-apoptosis accelerates viral release, triggered by depletion of host RNA binding proteins (RBPs) from nuclear RNA bound to replicating viral sequences. Methods: Information theory-based analysis of interactions between RBPs and individual sequences in the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), Influenza A (H3N1), HIV-1, and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Emerging role of artificial intelligence in therapeutics for COVID-19: a systematic review</strong> - To elucidate the role of artificial intelligence (AI) in therapeutics for coronavirus disease 2019 (COVID-19). Five databases were searched (December 2019-May 2020). We included both published and pre-print original articles in English that applied AI, machine learning or deep learning in drug repurposing, novel drug discovery, vaccine and antibody development for COVID-19. Out of 31 studies included, 16 studies applied AI for drug repurposing, whereas 10 studies utilized AI for novel drug…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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