Corpus overview


Overview

MeSH Disease

Human Phenotype

Pneumonia (304)

Fever (167)

Cough (107)

Hypertension (91)

Respiratory distress (91)


Transmission

age categories (586)

Transmission (495)

asymptotic cases (252)

gender (244)

fomite (192)


Seroprevalence
    displaying 51 - 60 records in total 2851
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    Unexpected Co-infection MESHD with Different Strains of SARS-CoV-2 in Patients with COVID-19

    Authors: Hayder O. Hashim; Mudher K. Mohammed; Mazin J. Mousa; Hadeer H. Abdulameer; Alaa T.S. Alhassnawi; Safa A. Hassan; Mohammed Baqur S. Al-Shuhaib

    id:10.20944/preprints202009.0375.v1 Date: 2020-09-17 Source: Preprints.org

    There is a rising global concern for the ongoing outbreak of SARS-CoV-2 due to its high transmission TRANS rate and unavailability of treatment. Through the binding of its spike glycoprotein with angiotensin type 2 (ACE2), SARS-CoV-2 can efficiently get in the cells of patients and start its pandemic cycle. Herein, the biological diversity of SARS-CoV-2 infection MESHD was assessed in Babylon province of Iraq by investigating the possible genetic variations of the spike glycoprotein. A specific coding region of 795 bp within the viral spike (S) gene was amplified from 19 patients who suffered from obvious symptoms of SARS-CoV-2 infection MESHD. Sequencing results identified fifteen novel nucleic acid variations with a variety of distributions within the investigated samples. The electropherograms of all the identified variations showed obvious co-infections MESHD with at least two different viral strains per sample. Within these co-infections, the majority of samples exhibited three nonsense single nucleotide polymorphism (SNP)s, p.301Cdel, p.380Ydel, and p.436del, which yielded three truncated SARS-CoV-2 spike glycoproteins of 301, 380, and 436 amino acids length, respectively. The network and phylogenetic analyses indicated that for all viral infections were derived from multi-ancestral origins. Results inferred from the specific clade-based tree entailed that some viral strains were derived from European G-clade sequences. In conclusion, our data demonstrated the absence of any single strain infection MESHD among all investigated viral samples in the studied area, which may entail a higher risk of SARS-CoV-2 in this country. Through the identified high frequency of truncated spike proteins, we suggest that defective SARS-CoV-2 may depend on helper strains having intact spikes in its infection. Alternatively, another putative ACE2-independent route of viral infection MESHD way also suggested. To the best of our knowledge, this is the first report to describe the co-infection MESHD of multiple strains of SARS-CoV-2 in patients with COVID-19.

    Topography, spike dynamics and nanomechanics of individual native SARS-CoV-2 virions MESHD

    Authors: Balint Kiss; Zoltan Kis; Bernadett Palyi; Miklos Kellermayer; Kevin R Bewley; Karen E Gooch; Stephanie Longet; Holly E Humphries; Robert J Watson; Laura Hunter; Kathryn A Ryan; Yper Hall; Laura Sibley; Charlotte Sarfas; Lauren Allen; Marilyn Aram; Emily Brunt; Phillip Brown; Karen R Buttigieg; Breeze E Cavell; Rebecca Cobb; Naomi S Coombes; Owen Daykin-Pont; Michael J Elmore; Konstantinos Gkolfinos; Kerry J Godwin; Jade Gouriet; Rachel Halkerston; Debbie J Harris; Thomas Hender; Catherine M.K. Ho; Chelsea L Kennard; Daniel Knott; Stephanie Leung; Vanessa Lucas; Adam Mabbutt; Alexandra L Morrison; Didier Ngabo; Jemma Paterson; Elizabeth J Penn; Steve Pullan; Irene Taylor; Tom Tipton; Stephen Thomas; Julia A Tree; Carrie Turner; Nadina Wand; Nathan R Wiblin; Sue Charlton; Bassam Hallis; Geoffrey Pearson; Emma L Rayner; Andrew G Nicholson; Simon G Funnell; Mike J Dennis; Fergus V Gleeson; Sally Sharpe; Miles W Carroll

    doi:10.1101/2020.09.17.302380 Date: 2020-09-17 Source: bioRxiv

    SARS-CoV-2, the virus responsible for the current COVID-19 pandemic, displays a corona-shaped layer of spikes which play fundamental role in the infection process. Recent structural data suggest that the spikes possess orientational freedom and the ribonucleoproteins segregate into basketlike structures. How these structural features regulate the dynamic and mechanical behavior of the native virion, however, remain unknown. By imaging and mechanically manipulating individual, native SARS-CoV-2 virions MESHD with atomic force microscopy, here we show that their surface displays a dynamic brush owing to the flexibility and rapid motion of the spikes. The virions are highly compliant and able to recover from drastic mechanical perturbations. Their global structure is remarkably temperature resistant, but the virion surface becomes progressively denuded of spikes upon thermal exposure. Thus, both the infectivity and thermal sensitivity SERO of SARS-CoV-2 rely on the dynamics and the mechanics of the virus.

    Monocytes and macrophages, targets of SARS-CoV-2: the clue for Covid-19 immunoparalysis

    Authors: Asma Boumaza; Laetitia Gay; Soraya Mezouar; Aissatou Bailo Diallo; Moise Michel; Benoit Desnues; Didier Raoult; Bernard LA SCOLA; Philippe Halfon; Joana Vitte; Daniel Olive; Jean-Louis Mege

    doi:10.1101/2020.09.17.300996 Date: 2020-09-17 Source: bioRxiv

    To date, the Covid-19 pandemic affected more than 18 million individuals and caused more than 690, 000 deaths. Its clinical expression is pleiomorphic and severity is related to age TRANS and comorbidities such as diabetes MESHD and hypertension HP hypertension MESHD. The pathophysiology of the disease relies on aberrant activation of immune system and lymphopenia HP lymphopenia MESHD that has been recognized as a prognosis marker. We wondered if the myeloid compartment was affected in Covid-19 and if monocytes and macrophages could be infected by SARS-CoV-2. We show here that SARS-CoV-2 efficiently infects MESHD monocytes and macrophages without any cytopathic effect. Infection was associated with the secretion of immunoregulatory cytokines (IL-6, IL-10, TGF-b) and the induction of a macrophagic specific transcriptional program characterized by the upregulation of M2-type molecules. In addition, we found that in vitro macrophage polarization did not account for the permissivity to SARS-CoV-2, since M1- and M2-type macrophages were similarly infected. Finally, in a cohort of 76 Covid-19 patients ranging from mild to severe clinical expression, all circulating monocyte subsets were decreased, likely related to massive emigration into tissues. Monocytes from Covid-19 patients exhibited decreased expression of HLA-DR and increased expression of CD163, irrespective of the clinical status. Hence, SARS-CoV-2 drives circulating monocytes and macrophages inducing immunoparalysis of the host for the benefit of Covid-19 disease progression.

    Distinct SARS-CoV-2 Antibody SERO Reactivity Patterns in Coronavirus Convalescent Plasma SERO Revealed by a Coronavirus Antigen Microarray

    Authors: Rafael Ramiro de Assis; Aarti Jain; Rie Nakajima; Algis Jasinskas; Saahir Khan; Larry J Dumont; Kathleen Kelly; Graham Simmons; Mars Stone; Clara Di Germanio; Michael P Busch; Philip L Felgner

    doi:10.1101/2020.09.16.300871 Date: 2020-09-17 Source: bioRxiv

    A coronavirus antigen microarray (COVAM) was constructed containing 11 SARS-CoV-2, 5 SARS-1, 5 MERS, and 12 seasonal coronavirus recombinant proteins. The array is designed to measure immunoglobulin isotype and subtype levels in serum SERO or plasma SERO samples against each of the individual antigens printed on the array. We probed the COVAM with COVID-19 convalescent plasma SERO (CCP) collected from 99 donors who recovered from a PCR+ confirmed SARS-CoV-2 infection MESHD. The results were analyzed using two computational approaches, a generalized linear model (glm) and Random Forest (RF) prediction model, to classify individual specimens as either Reactive or Non-Reactive against the SARS-CoV-2 antigens. A training set of 88 pre-COVID-19 specimens (PreCoV) collected in August 2019 and 102 positive specimens from SARS-CoV-2 PCR+ confirmed COVID-19 cases was used for these analyses. Results compared with an FDA emergency use authorized (EUA) SARS-CoV2 S1-based total Ig chemiluminescence immunoassay SERO (Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 Total, CoV2T) and with a SARS-CoV-2 S1-S2 spike-based pseudovirus micro neutralization assay (SARS-CoV-2 reporter viral particle neutralization titration (RVPNT) showed high concordance between the 3 assays. Three CCP specimens that were negative by the VITROS CoV2T immunoassay SERO were also negative by both COVAM and the RVPNT assay. Concordance between VITROS CoV2T and COVAM was 96%, VITROS CoV2T and RVPNT 93%, and RVPNT and COVAM 95%. The discordances were all weakly reactive samples near the cutoff threshold of the VITROS CoV2T immunoassay SERO. The multiplex COVAM allows CCP to be grouped according to antibody SERO reactivity patterns against 11 SARS-CoV-2 antigens. Unsupervised K-means analysis, via the gap statistics, as well as hierarchical clustering analysis revealed 3 main clusters with distinct reactivity intensities and patterns. These patterns were not recapitulated by adjusting the VITROS CoV2T or RVPNT assay thresholds. Plasma SERO classified according to these reactivity patterns may be better associated with CCP treatment efficacy than antibody SERO levels alone. The use of a SARS-CoV-2 antigen array may be useful to qualify CCP for administration as a treatment for acute COVID-19 and to interrogate vaccine immunogenicity and performance SERO in preclinical and clinical studies to understand and recapitulate antibody SERO responses associated with protection from infection and disease.

    Identification of novel antiviral drug combinations in vitro and tracking their development

    Authors: Aleksandr Ianevski; Rouan Yao; Svetlana Biza; Eva Zusinaite; Andres Mannik; Gaily Kivi; Anu Planken; Kristiina Kurg; Eva-Maria Tombak; Mart Ustav Jr.; Nastassia Shtaida; Evgeny Kulesskiy; Eunji Jo; Jaewon Yang; Hilde Lysvand; Kirsti Loseth; Valentyn Oksenych; Per Arne Aas; Tanel Tenson; Astra Vitkauskiene; Marc P. Windisch; Mona H Fenstad; Svein Arne Nordbo; Mart Ustav; Magnar Bjoras; Denis E Kainov

    doi:10.1101/2020.09.17.299933 Date: 2020-09-17 Source: bioRxiv

    Combination therapies have become a standard for the treatment for HIV and HCV infections MESHD. They are advantageous over monotherapies due to better efficacy and reduced toxicity MESHD, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections MESHD. Here, we identify several new synergistic combinations against emerging and re-emerging viral infections in vitro. We observed synergistic activity of nelfinavir with investigational drug EIDD-2801 and convalescent serum SERO against SARS-CoV-2 infection MESHD in human lung epithelial Calu-3 cells. We also demonstrated synergistic activity of vemurafenib combination with emetine, homoharringtonine, gemcitabine, or obatoclax against echovirus 1 infection MESHD in human lung epithelial A549 cells. We also found that combinations of sofosbuvir with brequinar and niclosamide were synergistic against HCV infection MESHD in hepatocyte derived Huh-7.5 cells, whereas combinations of monensin with lamivudine and tenofovir were synergistic against HIV-1 infection MESHD in human cervical TZM-bl cells. Finally, we present an online resource that summarizes novel and known antiviral drug combinations and their developmental status. Overall, the development of combinational therapies could have a global impact improving the preparedness and protection of the general population from emerging and re-emerging viral threats.

    Structural and Functional Comparison of SARS-CoV-2-Spike Receptor Binding Domain Produced in Pichia pastoris and Mammalian Cells

    Authors: - Argentinian AntiCovid Consortium; Claudia R. Arbeitman; Gabriela Auge; Matias Blaustein; Luis Bredeston; Enrique S. Corapi; Patricio O. Craig; Leandro A. Cossio; Liliana Dain; Fernanda Elias; Natalia B. Fernandez; Javier Gasulla; Natalia Gorojovsky; Gustavo E. Gudesblat; Maria G. Herrera; Lorena I. Ibañez; Tommy Idrovo; Matias Iglesias Rando; Laura Kamenetzky; Alejandro D Nadra; Diego G. Noseda; Carlos H. Pavan; Maria F. Pavan; Maria F. Pignataro; Ernesto Roman; Lucas A.M Ruberto; Natalia Rubinstein; Javier Santos; Francisco Velazquez; Alicia M. Zelada; Catherine M.K. Ho; Chelsea L Kennard; Daniel Knott; Stephanie Leung; Vanessa Lucas; Adam Mabbutt; Alexandra L Morrison; Didier Ngabo; Jemma Paterson; Elizabeth J Penn; Steve Pullan; Irene Taylor; Tom Tipton; Stephen Thomas; Julia A Tree; Carrie Turner; Nadina Wand; Nathan R Wiblin; Sue Charlton; Bassam Hallis; Geoffrey Pearson; Emma L Rayner; Andrew G Nicholson; Simon G Funnell; Mike J Dennis; Fergus V Gleeson; Sally Sharpe; Miles W Carroll

    doi:10.1101/2020.09.17.300335 Date: 2020-09-17 Source: bioRxiv

    The yeast Pichia pastoris is a cost-effective and easily scalable system for recombinant protein production. In this work we compared the conformation of the receptor binding domain (RBD) from SARS-CoV-2 Spike MESHD protein expressed in P. pastoris and in the well established HEK-293T mammalian cell system. RBD obtained from both yeast and mammalian cells was properly folded, as indicated by UV-absorption, circular dichroism and tryptophan fluorescence. They also had similar stability, as indicated by temperature-induced unfolding (observed Tm were 50 {degrees}C and 52 {degrees}C for RBD produced in P. pastoris and HEK-293T cells, respectively). Moreover, the stability of both variants was similarly reduced when the ionic strength was increased, in agreement with a computational analysis predicting that a set of ionic interactions may stabilize RBD structure. Further characterization by HPLC, size-exclusion chromatography and mass spectrometry revealed a higher heterogeneity of RBD expressed in P. pastoris relative to that produced in HEK-293T cells, which disappeared after enzymatic removal of glycans. The production of RBD in P. pastoris was scaled-up in a bioreactor, with yields above 45 mg/L of 90% pure protein, thus potentially allowing large scale immunizations to produce neutralizing antibodies SERO, as well as the large scale production of serological tests SERO for SARS-CoV-2.

    In Silico Screening for Natural Ligands to Non-Structural Nsp7 Conformers of Coronaviruses

    Authors: Rafael Blasco; Julio Coll

    doi:10.26434/chemrxiv.12952115.v1 Date: 2020-09-17 Source: ChemRxiv

    The non-structural protein 7 (nsp7) of Severe Acute Respiratory Syndrome MESHD (SARS) coronaviruses was selected as a new target to potentially interfere with viral replication. The nsp7s are one of the most conserved, unique and small coronavirus proteins having a critical, yet intriguing participation on the replication of the long viral RNA genome after complexing with nsp8 and nsp12. Despite the difficulties of having no previous binding pocket, two high-throughput virtual blind screening of 158240 natural compounds > 400 Da by AutoDock Vina against nsp7.1ysy identified 655 leads displaying predicted binding affinities between 10 to 1100 nM. The leads were then screened against 14 available conformations of nsp7 by both AutoDock Vina and seeSAR programs employing different binding score algorithms, to identify 20 consensus top-leads. Further in silico predictive analysis of physiological and toxicity ADMET criteria (chemical properties, adsorption, metabolism, toxicity) narrowed top-leads to a few drug-like ligands many of them showing steroid-like structures. A final optimization by search for structural similarity to the top drug-like ligand that were also commercially available, yielded a collection of predicted novel ligands with ~100-fold higher-affinity whose antiviral activity may be experimentally validated. Additionally, these novel nsp7-interacting ligands and/or their further optimized derivatives, may offer new tools to investigate the intriguing role of nsp7 on replication of coronaviruses.

    Mutational signatures in countries affected by SARS-CoV-2: Implications in host-pathogen interactome

    Authors: Syed Asad Rahman; Jasdeep Singh; Hina Singh; Anindita Basu; Michaela Gack; Savas Tay; Patricio O. Craig; Leandro A. Cossio; Liliana Dain; Fernanda Elias; Natalia B. Fernandez; Javier Gasulla; Natalia Gorojovsky; Gustavo E. Gudesblat; Maria G. Herrera; Lorena I. Ibañez; Tommy Idrovo; Matias Iglesias Rando; Laura Kamenetzky; Alejandro D Nadra; Diego G. Noseda; Carlos H. Pavan; Maria F. Pavan; Maria F. Pignataro; Ernesto Roman; Lucas A.M Ruberto; Natalia Rubinstein; Javier Santos; Francisco Velazquez; Alicia M. Zelada; Catherine M.K. Ho; Chelsea L Kennard; Daniel Knott; Stephanie Leung; Vanessa Lucas; Adam Mabbutt; Alexandra L Morrison; Didier Ngabo; Jemma Paterson; Elizabeth J Penn; Steve Pullan; Irene Taylor; Tom Tipton; Stephen Thomas; Julia A Tree; Carrie Turner; Nadina Wand; Nathan R Wiblin; Sue Charlton; Bassam Hallis; Geoffrey Pearson; Emma L Rayner; Andrew G Nicholson; Simon G Funnell; Mike J Dennis; Fergus V Gleeson; Sally Sharpe; Miles W Carroll

    doi:10.1101/2020.09.17.301614 Date: 2020-09-17 Source: bioRxiv

    We are in the midst of the third severe coronavirus outbreak caused by SARS-CoV-2 with unprecedented health and socio-economic consequences due to the COVID-19. Globally, the major thrust of scientific efforts has shifted to the design of potent vaccine and anti-viral candidates. Earlier genome analyses have shown global dominance of some mutations purportedly indicative of similar infectivity and transmissibility TRANS of SARS-CoV-2 worldwide. Using high-quality large dataset of 25k whole-genome sequences, we show emergence of new cluster of mutations as result of geographic evolution of SARS-CoV-2 in local population ({greater than or equal to}10%) of different nations. Using statistical analysis, we observe that these mutations have either significantly co-occurred in globally dominant strains or have shown mutual exclusivity in other cases. These mutations potentially modulate structural stability of proteins, some of which forms part of SARS-CoV-2-human interactome. The high confidence druggable host proteins are also up-regulated during SARS-CoV-2 infection MESHD. Mutations occurring in potential hot-spot regions within likely T-cell and B-cell epitopes or in proteins as part of host-viral interactome, could hamper vaccine or drug efficacy in local population. Overall, our study provides comprehensive view of emerging geo-clonal mutations which would aid researchers to understand and develop effective countermeasures in the current crisis.

    Baricitinib treatment resolves lower airway inflammation MESHD and neutrophil recruitment in SARS-CoV-2-infected rhesus MESHD macaques

    Authors: Timothy N Hoang; Maria Pino; Arun K Boddapati; Elise G Viox; Carly E Starke; Amit A Upadhyay; Sanjeev Gumber; Kathleen Busman-Sahay; Zachary Strongin; Justin L Harper; Gregory K Tharp; Kathryn L Pellegrini; Shannon Kirejczyk; Keivan Zandi; Sijia Tao; Tristan R Horton; Elizabeth N Beagle; Ernestine A Mahar; Michelle YH Lee; Joyce Cohen; Sherrie Jean; Jennifer S Wood; Fawn Connor-Stroud; Rachelle L Stammen; Olivia M Delmas; Shelly Wang; Kimberly A Cooney; Michael N Sayegh; Lanfang Wang; Daniela Weiskopf; Peter D Filev; Jesse Waggoner; Anne Piantadosi; Sudhir P Kasturi; Hilmi Al-Shakhshir; Susan P Ribeiro; Rafick P Sekaly; Rebecca D Levit; Jacob D Estes; Thomas H Vanderford; Raymond F Schinazi; Steven E Bosinger; Mirko Paiardini

    doi:10.1101/2020.09.16.300277 Date: 2020-09-16 Source: bioRxiv

    Effective therapeutics aimed at mitigating COVID-19 symptoms are urgently needed. SARS-CoV- 2 induced hypercytokinemia and systemic inflammation MESHD are associated with disease severity. Baricitinib, a clinically approved JAK1/2 inhibitor with potent anti-inflammatory properties is currently being investigated in COVID-19 human clinical trials. Recent reports suggest that baricitinib may also have antiviral activity in limiting viral endocytosis. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection MESHD. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages and tissues was not reduced with baricitinib. Type I IFN antiviral responses and SARS-CoV-2 specific T cell responses remained similar between the two groups. Importantly, however, animals treated with baricitinib showed reduced immune activation, decreased infiltration of neutrophils into the lung, reduced NETosis activity, and more limited lung pathology. Moreover, baricitinib treated animals had a rapid and remarkably potent suppression of alveolar MESHD macrophage derived production of cytokines and chemokines responsible for inflammation MESHD and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for severe inflammation MESHD induced by SARS-CoV-2 infection MESHD.

    Bromelain Inhibits SARS-CoV-2 Infection MESHD in VeroE6 Cells

    Authors: Satish Sagar; Ashok Kumar Rathinavel; William E. Lutz; Lucas R Struble; Surender Khurana; Andy T Schnaubelt; Nitish K Mishra; Chittibabu Guda; Mara J Broadhurst; St Patrick Reid; Kenneth W Bayles; Gloria E.O Borgstahl; Prakash Radhakrishnan; Keivan Zandi; Sijia Tao; Tristan R Horton; Elizabeth N Beagle; Ernestine A Mahar; Michelle YH Lee; Joyce Cohen; Sherrie Jean; Jennifer S Wood; Fawn Connor-Stroud; Rachelle L Stammen; Olivia M Delmas; Shelly Wang; Kimberly A Cooney; Michael N Sayegh; Lanfang Wang; Daniela Weiskopf; Peter D Filev; Jesse Waggoner; Anne Piantadosi; Sudhir P Kasturi; Hilmi Al-Shakhshir; Susan P Ribeiro; Rafick P Sekaly; Rebecca D Levit; Jacob D Estes; Thomas H Vanderford; Raymond F Schinazi; Steven E Bosinger; Mirko Paiardini

    doi:10.1101/2020.09.16.297366 Date: 2020-09-16 Source: bioRxiv

    Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2). The initial interaction between Transmembrane Serine Protease 2 (TMPRSS2) primed SARS-CoV-2 spike MESHD (S) protein and host cell receptor angiotensin-converting enzyme 2 (ACE-2) is a pre-requisite step for this novel coronavirus pathogenesis. Here, we expressed a GFP-tagged SARS-CoV-2 S-Ectodomain in Tni insect cells. That contained sialic acid-enriched N- and O-glycans. Surface resonance plasmon (SPR) and Luminex assay showed that the purified S-Ectodomain binding to human ACE-2 and immunoreactivity with COVID-19 positive samples. We demonstrate that bromelain (isolated from pineapple stem and used as a dietary supplement) treatment diminishes the expression of ACE-2 and TMPRSS2 in VeroE6 cells and dramatically lowers the expression of S-Ectodomain. Importantly, bromelain treatment reduced the interaction between S-Ectodomain and VeroE6 cells. Most importantly, bromelain treatment significantly diminished the SARS-CoV-2 infection MESHD in VeroE6 cells. Altogether, our results suggest that bromelain or bromelain rich pineapple stem may be used as an antiviral against COVID-19.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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