184 lines
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184 lines
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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>Conceptual flexibility and the meaning of Covid-19: evidence from the first Italian lockdown</strong> -
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<div>
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Several studies highlighted the flexible character of our conceptual system. However, less is known about the construction of meaning and the impact of novel concepts on the structuring of our conceptual space. We addressed these questions by collecting free listing data from Italian participants on a newly–and yet nowadays critical–introduced concept, i.e., Covid-19, during the first Italian lockdown. We also collected data for other five illness-related concepts. Our results show that Covid-19’s representation is mostly couched in the emotional sphere, predominantly evoking fear—linked to both possible health-related concerns and social-emotional ones. In contrast with initial public debates participants did not assimilate Covid-19 neither completely to severe illnesses (e.g., tumor) nor completely to mild illnesses (e.g., flu). Moreover, we also found that Covid-19 has shaped conceptual relations of other concepts in the illness domain, making certain features and associations more salient (e.g., flu-fear; disease-mask). Overall, our results show for the first time how a novel, real concept molds existing conceptual relations, testifying the malleability of our conceptual system.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/4ndb8/" target="_blank">Conceptual flexibility and the meaning of Covid-19: evidence from the first Italian lockdown</a>
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<li><strong>Pandemics Initially Spread Among People of High (not Low) Social Status: Evidence from COVID-19 and the Spanish Flu</strong> -
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According to a staple in the social sciences, pandemics particularly spread among people of lower social status. Challenging this staple, we hypothesize that it holds true in later phases of pandemics only. In the initial phases, by contrast, people of higher social status should be at the center of the spread. To test this hypothesis, we conducted two studies. In Study 1, we analyzed region-level COVID-19 infection data from 3,132 U.S. regions, 299 English regions, and 400 German regions. In Study 2, we analyzed historical data from 1,159,920 U.S. residents who witnessed the 1918/1919 Spanish Flu pandemic. Both studies supported our hypothesis in full. During the initial phases of both pandemics, the virus spread more rapidly among people of higher social status. In later phases, that effect consistently reversed, rendering people of lower social status the primarily exposed. Our results provide novel insights into the center of the spread during the critical initial phases of pandemics.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/vdqpa/" target="_blank">Pandemics Initially Spread Among People of High (not Low) Social Status: Evidence from COVID-19 and the Spanish Flu</a>
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</div></li>
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<li><strong>Microsecond simulation unravel the structural dynamics of SARS-CoV-2 Spike-C-terminal cytoplasmic tail (residues 1242-1273)</strong> -
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<div>
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Spike protein of human coronaviruses has been a vital drug and vaccine target. The multifunctionality of this protein including host receptor binding and apoptosis has been proved in several coronaviruses. It also interacts with other viral proteins such as membrane (M) protein through its C-terminal domain. The specific dibasic motif signal present in cytosolic region at C-terminal of spike protein helps it to localize within the endoplasmic reticulum (ER). However, the structural conformation of cytosolic region is not known in SARS-CoV-2 using which it interacts with other proteins and transporting vesicles. Therefore, we have demonstrated the conformation of cytosolic region and its dynamics through computer simulations up to microsecond timescale using OPLS and CHARMM forcefields. The simulations have revealed the unstructured conformation of cytosolic region (residues 1242-1273). Also, in temperature dependent replica-exchange molecular dynamics simulations it has shown to form secondary structures. We believe that our findings will surely help us understand the structure-function relationship of the spike protein's cytosolic region.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.11.426227v1" target="_blank">Microsecond simulation unravel the structural dynamics of SARS-CoV-2 Spike-C-terminal cytoplasmic tail (residues 1242-1273)</a>
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</div></li>
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<li><strong>Impact of South African 501.V2 Variant on SARS-CoV-2 Spike Infectivity and Neutralization: A Structure-based Computational Assessment</strong> -
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<div>
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Motivation: The SARS-CoV-2 variants emerging from South Africa (501.V2) and the UK (B.1.1.7) necessitate rapid assessment of the effects of the corresponding amino acid substitutions in the spike (S) receptor-binding domain (RBD) of the variants on the interactions with the human ACE2 receptor and monoclonal antibodies (mAbs) reported earlier to neutralize the spike. Results: Molecular modeling and simulations reveal that N501Y, shared by both variants, increases ACE2 binding affinity, and may impact the collective dynamics of the ACE2-RBD complex, occupying a central hinge site that modulates the overall dynamics of the complex. In contrast, the substitutions K417N and E484K in the South African variant 501.V2 would reduce the ACE2-binding affinity by abolishing two interfacial salt bridges that facilitate RBD binding to ACE2, K417(S)-D30(ACE2) and E484 (S)-K31(ACE2). These two mutations may thus be more than compensating the attractive effect induced by N501Y, overall resulting in an ACE2-binding affinity comparable to that of the wildtype RBD. Further analysis of the impact of these mutations on the interactions with mAbs targeting the spike indicate that the substitutions K417N and E484K may also abolish the salt bridges between the spike and selected mAbs, such as REGN10933, BD23, H11_H4, and C105, thus reducing the binding affinity and effectiveness of these mAbs.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.10.426143v1" target="_blank">Impact of South African 501.V2 Variant on SARS-CoV-2 Spike Infectivity and Neutralization: A Structure-based Computational Assessment</a>
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</div></li>
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<li><strong>Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA SARS 2 S in preclinical vaccination</strong> -
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<div>
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The severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavirus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evaluation with our vector vaccine based on vaccinia virus MVA against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here, we describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust synthesis of S antigen, make it a suitable candidate vaccine for industrial scale production. Vaccinated mice produced S antigen-specific CD8+ T cells and serum antibodies binding to S glycoprotein that neutralized SARS-CoV 2. Prime-boost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.09.426032v1" target="_blank">Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA SARS 2 S in preclinical vaccination</a>
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</div></li>
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<li><strong>Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces shedding of SARS-CoV-2 D614G in rhesus macaques</strong> -
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<div>
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Intramuscular vaccination with ChAdOx1 nCoV-19/AZD1222 protected rhesus macaques against pneumonia but did not reduce shedding of SARS-CoV-2. Here we investigate whether intranasally administered ChAdOx1 nCoV-19 reduces shedding, using a SARS-CoV-2 virus with the D614G mutation in the spike protein. Viral load in swabs obtained from intranasally vaccinated hamsters was significantly decreased compared to controls and no viral RNA or infectious virus was found in lung tissue, both in a direct challenge and a transmission model. Intranasal vaccination of rhesus macaques resulted in reduced shedding and a reduction in viral load in bronchoalveolar lavage and lower respiratory tract tissue. In conclusion, intranasal vaccination reduced shedding in two different SARS-CoV-2 animal models, justifying further investigation as a potential vaccination route for COVID-19 vaccines.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.09.426058v1" target="_blank">Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces shedding of SARS-CoV-2 D614G in rhesus macaques</a>
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</div></li>
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<li><strong>COVID-19 Severity Is Associated with Differential Antibody Fc-mediated Innate Immune Functions</strong> -
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<div>
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Beyond neutralization, antibodies elicit several innate immune functions including complement deposition (ADCD), phagocytosis (ADCP), and cytotoxicity (ADCC). These functions can be both beneficial (by clearing pathogens) and/or detrimental (by inducing inflammation). We tested the possibility that qualitative differences in SARS-CoV-2 specific antibody-mediated innate immune functions contribute to Coronavirus disease 2019 (COVID-19) severity. We found that antibodies from hospitalized COVID-19 patients elicited higher ADCD but lower ADCP compared to antibodies from non-hospitalized COVID-19 patients. Consistently, higher ADCD was associated with higher systemic inflammation during COVID-19. Our study points to qualitative, differential features of anti-SARS-CoV-2 antibodies as potential contributors to COVID-19 severity.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.11.426209v1" target="_blank">COVID-19 Severity Is Associated with Differential Antibody Fc-mediated Innate Immune Functions</a>
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</div></li>
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<li><strong>Immunogenicity and Protective Efficacy of an Intranasal Live-attenuated Vaccine Against SARS-CoV-2 in Preclinical Animal Models</strong> -
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The global deployment of an effective and safe vaccine is currently a public health priority to curtail the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we evaluated a Newcastle disease virus (NDV)-based intranasal vectored-vaccine in mice and hamsters for its immunogenicity, safety and protective efficacy in challenge studies with SARS-CoV-2. The recombinant (r)NDV-S vaccine expressing spike (S) protein of SARS-CoV-2 administrated via intranasal route in mice induced high levels of SARS-CoV-2-specific neutralizing immunoglobulin A (IgA) and IgG2a antibodies and T cell-mediated immunity. Hamsters vaccinated with two doses of vaccine showed complete protection from clinical disease including lung infection, inflammation, and pathological lesions after SARS-CoV-2 challenge. Importantly, a single or double dose of intranasal rNDV-S vaccine completely blocked SARS-CoV-2 shedding in nasal turbinate and lungs within 4 days of vaccine administration in hamsters. Taken together, intranasal administration of rNDV-S has the potential to control infection at the site of inoculation, which should prevent both the clinical disease and transmission to halt the spread of the COVID-19 pandemic.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.08.425974v1" target="_blank">Immunogenicity and Protective Efficacy of an Intranasal Live-attenuated Vaccine Against SARS-CoV-2 in Preclinical Animal Models</a>
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<li><strong>Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class</strong> -
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<div>
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Antibodies with heavy chains that derive from the VH1-2 gene constitute some of the most potent SARS-CoV-2-neutralizing antibodies yet identified. To provide insight into whether these genetic similarities inform common modes of recognition, we determined structures of the SARS-CoV-2 spike in complex with three VH1-2-derived antibodies: 2-15, 2-43, and H4. All three utilized VH1-2-encoded motifs to recognize the receptor-binding domain (RBD), with heavy chain N53I enhancing binding and light chain tyrosines recognizing F486RBD. Despite these similarities, class members bound both RBD up and down conformations of the spike, with a subset of antibodies utilizing elongated CDRH3s to recognize glycan N343 on a neighboring RBD - a quaternary interaction accommodated by an increase in RBD separation of up to 12 angstrom. The VH1-2-antibody class thus utilizes modular recognition encoded by modular genetic elements to effect potent neutralization, with VH-gene component specifying recognition of RBD and CDRH3 component specifying quaternary interactions.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.11.426218v1" target="_blank">Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class</a>
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<li><strong>Molecular Dynamics Analysis of a Flexible Loop at the Binding Interface of the SARS-CoV-2 Spike Protein Receptor-Binding Domain</strong> -
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<div>
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Since the identification of the SARS-CoV-2 virus as the causative agent of the current COVID-19 pandemic, considerable effort has been spent characterizing the interaction between the Spike protein receptor-binding domain (RBD) and the human angiotensin converting enzyme 2 (ACE2) receptor. This has provided a detailed picture of the end point structure of the RBD-ACE2 binding event, but what remains to be elucidated is the conformation and dynamics of the RBD prior to its interaction with ACE2. In this work we utilize molecular dynamics simulations to probe the flexibility and conformational ensemble of the unbound state of the receptor-binding domain from SARS-CoV-2 and SARS-CoV. We have found that the unbound RBD has a localized region of dynamic flexibility in Loop 3 and that mutations identified during the COVID-19 pandemic in Loop 3 do not affect this flexibility. We use a loop-modeling protocol to generate and simulate novel conformations of the CoV2-RBD Loop 3 region that sample conformational space beyond the ACE2 bound crystal structure. This has allowed for the identification of interesting substates of the unbound RBD that are lower energy than the ACE2-bound conformation, and that block key residues along the ACE2 binding interface. These novel unbound substates may represent new targets for therapeutic design.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.08.425965v1" target="_blank">Molecular Dynamics Analysis of a Flexible Loop at the Binding Interface of the SARS-CoV-2 Spike Protein Receptor-Binding Domain</a>
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<li><strong>Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2 and heparan sulfate</strong> -
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A main clinical parameter of Covid-19 pathophysiology is hypoxia. Here we show that hypoxia decreases the attachment of the receptor binding domain (RBD) and the S1 subunit (S1) of the spike protein to epithelial cells. In Vero E6 cells, hypoxia reduces the protein levels of ACE2, which might in part explain the observed reduction of the infection rate. However, hypoxia also inhibits the binding of the spike to human lung epithelial cells lacking ACE2 expression, indicating that hypoxia modulates the expression of additional binding partners of SARS-CoV-2. We show that hypoxia also decreases the total cell surface levels of heparan sulfate, a known attachment receptor of SARS-CoV-2, by reducing the expression of syndecan-1 and syndecan3, the main proteoglycans containing heparan sulfate. Our study indicates that hypoxia acts to prevent SARS-CoV-2 infection, suggesting that the hypoxia signaling pathway might offer therapeutic opportunities for the treatment of Covid-19.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.09.426021v1" target="_blank">Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2 and heparan sulfate</a>
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<li><strong>Potent SARS-CoV-2 Neutralizing Antibodies Directed Against Spike N-Terminal Domain Target a Single Supersite</strong> -
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Numerous antibodies that neutralize SARS-CoV-2 have been identified, and these generally target either the receptor-binding domain (RBD) or the N-terminal domain (NTD) of the viral spike. While RBD-directed antibodies have been extensively studied, far less is known about NTD-directed antibodies. Here we report cryo-EM and crystal structures for seven potent NTD-directed neutralizing antibodies in complex with spike or isolated NTD. These structures defined several antibody classes, with at least one observed in multiple convalescent donors. The structures revealed all seven antibodies to target a common surface, bordered by glycans N17, N74, N122, and N149. This site - formed primarily by a mobile {beta}-hairpin and several flexible loops - was highly electropositive, located at the periphery of the spike, and the largest glycan-free surface of NTD facing away from the viral membrane. Thus, in contrast to neutralizing RBD-directed antibodies that recognize multiple non-overlapping epitopes, potent NTD-directed neutralizing antibodies target a single supersite.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.10.426120v1" target="_blank">Potent SARS-CoV-2 Neutralizing Antibodies Directed Against Spike N-Terminal Domain Target a Single Supersite</a>
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<li><strong>The landscape of human brain immune response in patients with severe COVID-19</strong> -
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In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between brain tropism, neuroinflammation and host immune response has not been well characterized. We analyzed 68,557 single-nucleus transcriptomes from three brain regions (dorsolateral prefrontal cortex, medulla oblongata and choroid plexus) and identified an increased proportion of stromal cells and monocytes in the choroid plexus of COVID-19 patients. Differential gene expression, pseudo-temporal trajectory and gene regulatory network analyses revealed microglial transcriptome perturbations, mediating a range of biological processes, including cellular activation, mobility and phagocytosis. Quantification of viral spike S1 protein and SARS-CoV-2 transcripts did not support the notion of brain tropism. Overall, our findings suggest extensive neuroinflammation in patients with acute COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.01.08.425999v1" target="_blank">The landscape of human brain immune response in patients with severe COVID-19</a>
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<li><strong>Ca2+-dependent mechanism of membrane insertion and destabilization by the SARS-CoV-2 fusion peptide</strong> -
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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 Ca2+ ions to the FPs of corona viruses, but the mechanisms of membrane insertion and destabilization remain unclear. We have predicted the preferred positions of Ca2+ binding to the SARS-CoV-2-FP, the role of Ca2+ ions in mediating peptide-membrane interactions, the preferred mode of insertion of the Ca2+-bound SARS-CoV-2-FP and consequent effects on the lipid bilayer from extensive atomistic molecular dynamics (MD) simulations and trajectory analyses. In a systematic sampling of the interactions of the Ca2+-bound peptide models with lipid membranes SARS-CoV-2-FP penetrated the bilayer and disrupted its organization only in two modes involving different structural domains. In one, the hydrophobic residues F833/I834 from the middle region of the peptide are inserted. In the other, more prevalent mode, the penetration involves residues L822/F823 from the LLF motif which is conserved in CoV-2-like viruses, and is achieved by the binding of Ca2+ ions to the D830/D839 and E819/D820 residue pairs. FP penetration is shown to modify the molecular organization in specific areas of the bilayer, and the extent of membrane binding of the SARS-CoV-2 FP is significantly reduced in the absence of Ca2+ ions. These findings provide novel mechanistic insights regarding the role of Ca2+ in mediating SARS-CoV-2 fusion and provide a detailed structural platform to aid the ongoing efforts in rational design of compounds to inhibit SARS-CoV-2 cell entry.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.12.03.410472v2" target="_blank">Ca2+-dependent mechanism of membrane insertion and destabilization by the SARS-CoV-2 fusion peptide</a>
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<li><strong>CoronaHiT: High throughput sequencing of SARS-CoV-2 genomes</strong> -
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The COVID-19 pandemic has spread to almost every country in the world since it started in China in late 2019. Controlling the pandemic requires a multifaceted approach including whole genome sequencing to support public health interventions at local and national levels. One of the most widely used methods for sequencing is the ARTIC protocol, a tiling PCR approach followed by Oxford Nanopore sequencing (ONT) of up to 96 samples at a time. There is a need, however, for a flexible, platform agnostic, method that can provide multiple throughput options depending on changing requirements as the pandemic peaks and troughs. Here we present CoronaHiT, a method capable of multiplexing up to 96 small genomes on a single MinION flowcell or >384 genomes on Illumina NextSeq, using transposase mediated addition of adapters and PCR based addition of barcodes to ARTIC PCR products. We demonstrate the method by sequencing 95 and 59 SARS-CoV-2 genomes for routine and rapid outbreak response runs, respectively, on Nanopore and Illumina platforms and compare to the standard ARTIC LoCost nanopore method. Of the 154 samples sequenced using the three approaches, genomes with [≥] 90% coverage (GISAID criteria) were generated for 64.3% of samples for ARTIC LoCost, 71.4% for CoronaHiT-ONT, and 76.6% for CoronaHiT-Illumina and have almost identical clustering on a maximum likelihood tree. In conclusion, we demonstrate that CoronaHiT can multiplex up to 96 SARS-CoV-2 genomes per MinION flowcell and that Illumina sequencing can be performed on the same libraries, which will allow significantly higher throughput. CoronaHiT provides increased coverage for higher Ct samples, thereby increasing the number of high quality genomes that pass the GISAID QC threshold. This protocol will aid the rapid expansion of SARS-CoV-2 genome sequencing globally, to help control the pandemic.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.06.24.162156v2" target="_blank">CoronaHiT: High throughput sequencing of SARS-CoV-2 genomes</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>Rapid Diagnosis of COVID-19 by Chemical Analysis of Exhaled Air</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Diagnostic Test: Performance evaluation (sensitivity and specificity) for COVID-19 diagnosis of the Vocus PTR-TOF process<br/><b>Sponsor</b>: Hospices Civils de Lyon<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 Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adult</strong> - <b>Condition</b>: Covid19 Vaccine<br/><b>Interventions</b>: Biological: MVC-COV1901(S protein with adjuvant); Biological: MVC-COV1901(Saline)<br/><b>Sponsor</b>: Medigen Vaccine Biologics Corp.<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>The Safety and Efficacy of Pyronaridine-artesunate (Pyramax® or Artecom®)in COVID-19 Patients</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Artecom® (pyronaridine-artesunate); Drug: Placebo<br/><b>Sponsor</b>: Shin Poong Pharmaceutical Co. Ltd.<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>Safety and Immunogenicity of Two Different Strengths of the Inactivated COVID-19 Vaccine ERUCOV-VAC</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Interventions</b>: Biological: ERUCOV-VAC; Other: Placebo Vaccine<br/><b>Sponsors</b>: Health Institutes of Turkey; TC Erciyes University<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>Study to Evaluate the Safety, Tolerability, and Efficacy of BGE-175 in Participants ≥ 60 Years of Age and Hospitalized With Coronavirus Disease 2019 (COVID-19) That Are Not in Respiratory Failure</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: BGE-175; Other: Placebo<br/><b>Sponsor</b>: BioAge Labs, 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>The Effect of Deep Breathing Exercise on Dyspnea, Anxiety and Quality of Life in Patients Treated for COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Deep Breathing Exercise with Triflo<br/><b>Sponsor</b>: Ankara University<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>RU Anti-SARS-CoV-2 (COVID-19) mAbs in Healthy Volunteers</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Biological: C144-LS and C-135-LS<br/><b>Sponsor</b>: Rockefeller University<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>Study in Adults to Determine the Safety and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, Given in Combination With rAd26-S, Recombinant Adenovirus Type 26 Component of Gam-COVID-Vac Vaccine, for the Prevention of COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AZD1222; Biological: rAd26-S<br/><b>Sponsors</b>: R-Pharm; AstraZeneca<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>Surgical Face Mask Effects in Patients With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Other: Sit-To-Stand test<br/><b>Sponsor</b>: Cliniques universitaires Saint-Luc- Université Catholique de Louvain<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>Glutathione, Oxidative Stress and Mitochondrial Function in COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Dietary Supplement: Glycine; Dietary Supplement: N-acetylcysteine; Dietary Supplement: Alanine<br/><b>Sponsor</b>: Baylor College of Medicine<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>RespiraConNosotros:a Mobile Application for COVID-19 Respiratory Rehabilitation.</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Other: Breathing exercise<br/><b>Sponsor</b>: University of Salamanca<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 of Favipiravir in Treatment of Mild & Moderate COVID-19 Infection in Nepal</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Favipiravir; Drug: Placebo; Drug: Remdesivir<br/><b>Sponsor</b>: Nepal Health Research Council<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>Dendritic Cell Vaccine, AV-COVID-19, to Prevent COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AV-COVID-19; Other: GM-CSF<br/><b>Sponsors</b>: Aivita Biomedical, Inc.; PT AIVITA Biomedika Indonesia; Indonesia Ministry of Health; National Institute of Health Research and Development, Ministry of Health Republic of Indonesia<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>Study of the Immunological and Virological Response of Patients With COVID-19 and Presenting an Asymptomatic or Pauci-symptomatic Form (AMBUCOV)</strong> - <b>Conditions</b>: Covid19; SARS-CoV-2<br/><b>Interventions</b>: Diagnostic Test: Blood count; Diagnostic Test: Blood collection; Diagnostic Test: Nasopharyngeal swab; Diagnostic Test: Saliva samples; Diagnostic Test: Faeces samples; Genetic: Genetic blood collection; Other: Data collection<br/><b>Sponsors</b>: Assistance Publique - Hôpitaux de Paris; Fonds IMMUNOV<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 Real World Study of Bamlanivimab in Participants With Mild-to-moderate Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Bamlanivimab<br/><b>Sponsors</b>: Eli Lilly and Company; AbCellera Biologics Inc.<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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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>Upregulation of DUSP6 impairs infectious bronchitis virus replication by negatively regulating ERK pathway and promoting apoptosis</strong> - Elucidating virus-cell interactions is fundamental to understanding viral replication and identifying targets for therapeutic control of viral infection. The extracellular signal-regulated kinase (ERK) pathway has been shown to regulate pathogenesis during many viral infections, but its role during coronavirus infection is undetermined. Infectious bronchitis virus is the representative strain of Gammacoronavirus, which causes acute and highly contagious diseases in the poultry farm. In this...</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 existing drugs: identification of SARS-CoV-2 3C-like protease inhibitors</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). Since its emergence, the COVID-19 pandemic has not only distressed medical services but also caused economic upheavals, marking urgent the need for effective therapeutics. The experience of combating SARS-CoV and MERS-CoV has shown that inhibiting the 3-chymotrypsin-like protease (3CLpro) blocks the replication of the virus. Given the well-studied properties of FDA-approved drugs,...</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>Experimental Models to Study COVID-19 Effect in Stem Cells</strong> - The new strain of coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) emerged in 2019 and hence is often referred to as coronavirus disease 2019 (COVID-19). This disease causes hypoxic respiratory failure and acute respiratory distress syndrome (ARDS), and is considered as the cause of a global pandemic. Very limited reports in addition to ex vivo model systems are available to understand the mechanism of action of this virus, which can be used for testing of any drug...</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>Drug Repurposing: Dipeptidyl Peptidase IV (DPP4) Inhibitors as Potential Agents to Treat SARS-CoV-2 (2019-nCoV) Infection</strong> - The current outbreak of severe acute respiratory distress syndrome (SARS) or nCOVID-19 pandemic, caused by the coronavirus-2 (CoV-2), continues to wreak havoc globally. As novel vaccines are being discovered and developed, small molecule drugs still constitute a viable treatment option for SARS-CoV-2 infections due to their advantages such as superior patient compliance for oral therapies, reduced manufacturing costs and ease of large scale distribution due to better stability and storage...</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>Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease</strong> - Neutrophils are primary effector cells of innate immunity and fight infection by phagocytosis and degranulation. Activated neutrophils also release neutrophil extracellular traps (NETs) in response to a variety of stimuli. These NETs are net-like complexes composed of cell-free DNA, histones and neutrophil granule proteins. Besides the evolutionarily conserved mechanism to capture and eliminate pathogens, NETs are also associated with pathophysiological processes of various diseases. Here, we...</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 in teriflunomide-treated patients with multiple sclerosis: A case report and literature review</strong> - CONCLUSION: Available data suggest that teriflunomide therapy should not be discontinued in MS patients who develop SARS-CoV-2 infection, also in presence of significant comorbidities or clinical conditions requiring hospitalization. Additional studies are necessary to assess if the drug can also have a protective role 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>A systematic review of experimental evidence for antiviral effects of ivermectin and an in-silico analysis of ivermectin's possible mode of action against SARS-CoV-2</strong> - Viral infections remain a major cause of economic loss with an unmet need for novel therapeutic agents. Ivermectin is a putative antiviral compound; the proposed mechanism is the inhibition of nuclear translocation of viral proteins, facilitated by mammalian host importins, a necessary process for propagation of infections. We systematically reviewed the evidence for the applicability of ivermectin against viral infections including SARS-CoV-2 regarding efficacy, mechanisms and selective...</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>ACE2-derived peptides interact with the RBD domain of SARS-CoV-2 spike glycoprotein, disrupting the interaction with the human ACE2 receptor</strong> - Vaccines could be the solution to the current SARS-CoV-2 outbreak. However, some studies have shown that the immunological memory only lasts three months. Thus, it is imperative to develop pharmacological treatments to cope with COVID-19. Here, the in silico approach by molecular docking, dynamic simulations and quantum biochemistry revealed that ACE2-derived peptides strongly interact with the SARS-CoV-2 RBD domain of spike glycoprotein (S-RBD). ACE2-Dev-PepI, ACE2-Dev-PepII, ACE2-Dev-PepIII...</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>Ifenprodil Stereoisomers: Synthesis, Absolute Configuration, and Correlation with Biological Activity</strong> - Ifenprodil (1) is a potent GluN2B-selective N-methyl-d-aspartate (NMDA) receptor antagonist that is used as a cerebral vasodilator and has been examined in clinical trials for the treatment of drug addiction, idiopathic pulmonary fibrosis, and COVID-19. To correlate biological data with configuration, all four ifenprodil stereoisomers were prepared by diastereoselective reduction and subsequent separation of enantiomers by chiral HPLC. The absolute configuration of ifenprodil stereoisomers was...</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>ACE-2-interacting Domain of SARS-CoV-2 (AIDS) Peptide Suppresses Inflammation to Reduce Fever and Protect Lungs and Heart in Mice: Implications for COVID-19 Therapy</strong> - COVID-19 is an infectious respiratory illness caused by the virus strain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and until now, there is no effective therapy against COVID-19. Since SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) for entering into host cells, to target COVID-19 from therapeutic angle, we engineered a hexapeptide corresponding to the ACE2-interacting domain of SARS-CoV-2 (AIDS) that inhibits the association between receptor-binding...</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>Potentials of Interferons and Hydroxychloroquine for the Prophylaxis and Early Treatment of COVID-19</strong> - The symptoms of the COVID-19 range from asymptomatic or mild disease to severe disease that results in acute respiratory distress syndrome (ARDS) and eventually death. Understanding the molecular mechanisms responsible for the progression from mild to severe disease is the key to decreasing the mortality of COVID-19. Compared to mild cases, severe cases of the COVID-19 have decreased interferon (IFN) α, β, λ production. Type I (IFN α/β) and III IFNs (λ) work coordinately to induce inhibition of...</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molecular Docking Studies on the Anti-viral Effects of Compounds From Kabasura Kudineer on SARS-CoV-2 3CL(pro)</strong> - The COVID-19 has now been declared a global pandemic by the World Health Organization. No approved drug is currently available; therefore, an urgent need has been developed for any antiviral therapy for COVID-19. Main protease 3CL^(pro) of this novel Coronavirus (SARS-CoV-2) play a critical role in the disease propagation, and hence represent a crucial target for the drug discovery. Herein, we have applied a bioinformatics approach for drug repurposing to identify the possible potent inhibitors...</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>Computational Prediction of Potential Inhibitors of the Main Protease of SARS-CoV-2</strong> - The rapidly developing pandemic, known as coronavirus disease 2019 (COVID-19) and caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently spread across 213 countries and territories. This pandemic is a dire public health threat-particularly for those suffering from hypertension, cardiovascular diseases, pulmonary diseases, or diabetes; without approved treatments, it is likely to persist or recur. To facilitate the rapid discovery of inhibitors with clinical...</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>Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (M(pro)) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study</strong> - Since the outbreak of the COVID-19 (coronavirus disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants using a molecular docking approach to inhibit the main protease (M^(pro)) and spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the...</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>In silico evaluation of flavonoids as effective antiviral agents on the spike glycoprotein of SARS-CoV-2</strong> - The novel coronavirus pandemic has spread over in 213 countries as of July 2020. Approximately 12 million people have been infected so far according to the reports from World Health Organization (WHO). Preventive measures are being taken globally to avoid the rapid spread of virus. In the current study, an in silico approach is carried out as a means of inhibiting the spike protein of the novel coronavirus by flavonoids from natural sources that possess both antiviral and anti-inflammatory...</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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<ul>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Covid 19 - Chewing Gum</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313269181">link</a></p></li>
|
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313300659">link</a></p></li>
|
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19</strong> - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN313339294">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313251184">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU313251182">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>抑制病毒受体ACE2的COVID-19防治药物及其应用</strong> - 本发明提供了一种抑制病毒受体ACE2的COVID‑19防治药物及其应用。具体地说,本发明提供了中药鹅不食草在制备调节ACE2表达量的药物中的应用。本发明还提供了中药鹅不食草单独或与其它药物组合在制备COVID‑19防治药物中的应用。本发明发现鹅不食草能够使正常肺上皮细胞中ACE2的表达降低,从而降低新型冠状病毒(SARS‑CoV‑2)感染的风险,发挥预防SARS‑CoV‑2感染及治疗COVID‑19的作用。中药鹅不食草成本低,毒副作用小,疗效显著,为COVID‑19的治疗提供了新策略。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN313773195">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>"AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2."</strong> - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN312324209">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>제2형 중증급성호흡기증후군 코로나바이러스 감염 질환의 예방 또는 치료용 조성물</strong> - 본 발명은 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염; 및 글루카곤 수용체 작용제(glucagon receptor agonist), 위 억제 펩타이드(gastric inhibitory peptide, GIP), 글루카곤-유사 펩타이드 1(glucagon-like peptide 1, GLP-1) 및 글루카곤 수용체/위 억제 펩타이드/글루카곤-유사 펩타이드 1(Glucagon/GIP/GLP-1) 삼중 완전 작용제(glucagon receptors, gastric inhibitory peptide and glucagon-like peptide 1 (Glucagon/GIP/GLP-1) triple full agonist)로 이루어진 군으로부터 선택된 1종 이상;을 포함하는 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환 예방 또는 치료용 약학적 조성물을 제공한다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR313434044">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Haptens, hapten conjugates, compositions thereof and method for their preparation and use</strong> - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU311608060">link</a></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mundschutz für Brillenträger und Brillenadapter</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Mundschutz bestehend aus einem Abdeckteil für den Mund- und gegebenenfalls den Nasenbereich des Gesichts und einem Bandteil mit mindestens einem Halteband, welches mit den Seiten des Abdeckteil verbunden ist und zur Befestigung des Mundschutzes dient, wobei das Halteband am seitlichen Ende des Abdeckteils fixiert ist und eine Schlaufe bildet, dadurch gekennzeichnet, dass an der Schlaufe des Haltebands ein Clip befestigt ist.</p></li>
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<li><a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=DE313866570">link</a></li>
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