Corpus overview


Overview

MeSH Disease

HGNC Genes

Transmission

age categories (4237)

Transmission (3651)

gender (1909)

fomite (1442)

contact tracing (1365)


Seroprevalence
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    The N-glycosylation sites and Glycan-binding ability of S-protein HGNC in SARS-CoV-2 Coronavirus

    Authors: Wentian Chen; Ziye Hui; Xiameng Ren; Yijie Luo; Jian Shu; Hanjie Yu; Zheng Li

    doi:10.1101/2020.12.01.406025 Date: 2020-12-01 Source: bioRxiv

    The emerging acute respiratory disease MESHD, COVID-19 MESHD, caused by SARS-CoV-2 Coronavirus (SARS2 CoV) has spread fastly all over the word. As a member of RNA viruses, the glycosylation of envelope glycoprotein plays the crucial role in protein folding, evasing host immune system, invading host cell membrane, even affecting host preference. Therefore, detail glyco-related researches have been adopted in the Spike protein ( S-protein HGNC) of SARS2 CoV from the bioinformatic perspective. Phylogenic analysis of S-protein HGNC sequences revealed the evolutionary relationship of N-glycosylation sites in different CoVs. Structural comparation of S-proteins indicated their similarity and distributions of N-glycosylation sites. Further potential sialic acid or galactose affinity domains have been described in the S-protein HGNC by docking analysis. Molecular dynamic simulation for the glycosylated complexus of S-protein HGNC- ACE2 HGNC implied that the complicate viral binding of receptor-binding domain may be influenced by peripheric N-glycans from own and adjacent monoers. These works will contribute to investigate the N-glycosylation in S-protein HGNC and explain the highly contagious of COVID-19 MESHD.

    Guidelines for accurate genotyping of SARS-CoV-2 using amplicon-based sequencing of clinical samples

    Authors: Slawomir Kubik; Ana Claudia Marques; Xiaobin Xing; Janine Silvery; Claire Bertelli; Flavio De Maio; Spyros Pournaras; Tom Burr; Yannis Duffourd; Helena Siemens; Chakib Alloui; Lin Song; Yvan Wenger; Alexandra Saitta; Morgane Macheret; Ewan W Smith; Philippe Menu; Marion Brayer; Lars M Steinmetz; Ali Si-Mohammed; Josiane Chuisseu; Richard Stevens; Pantelis Constantoulakis; Michela Sali; Gilbert Greub; Carsten Tiemann; Vicent Pelechano; Adrian Willig; Zhenyu Xu

    doi:10.1101/2020.12.01.405738 Date: 2020-12-01 Source: bioRxiv

    Background: SARS-CoV-2 genotyping has been instrumental to monitor virus evolution and transmission TRANS during the pandemic. The reliability of the information extracted from the genotyping efforts depends on a number of aspects, including the quality of the input material, applied technology and potential laboratory-specific biases. These variables must be monitored to ensure genotype reliability. The current lack of guidelines for SARS-CoV-2 genotyping leads to inclusion of error-containing genome sequences in studies of viral spread and evolution. Results: We used clinical samples and synthetic viral genomes to evaluate the impact of experimental factors, including viral load and sequencing depth, on correct sequence determination using an amplicon-based approach. We found that at least 1000 viral genomes are necessary to confidently detect variants in the genome at frequencies of 10% or higher. The broad applicability of our recommendations was validated in >200 clinical samples from six independent laboratories. The genotypes of clinical isolates with viral load above the recommended threshold cluster by sampling location and period. Our analysis also supports the rise in frequency of 20A.EU1 and 20A.EU2, two recently reported European strains whose dissemination was favoured by travelling TRANS during the summer 2020. Conclusions: We present much-needed recommendations for reliable determination of SARS-CoV-2 genome sequence and demonstrate their broad applicability in a large cohort of clinical samples.

    Role of Long-range Allosteric Communication in Determining the Stability and Disassembly of SARS-COV-2 in Complex with ACE2

    Authors: Mauro Lorenzo Mugnai; Clark Templeton; Ron Elber; Dave Thirumalai; Claire Bertelli; Flavio De Maio; Spyros Pournaras; Tom Burr; Yannis Duffourd; Helena Siemens; Chakib Alloui; Lin Song; Yvan Wenger; Alexandra Saitta; Morgane Macheret; Ewan W Smith; Philippe Menu; Marion Brayer; Lars M Steinmetz; Ali Si-Mohammed; Josiane Chuisseu; Richard Stevens; Pantelis Constantoulakis; Michela Sali; Gilbert Greub; Carsten Tiemann; Vicent Pelechano; Adrian Willig; Zhenyu Xu

    doi:10.1101/2020.11.30.405340 Date: 2020-12-01 Source: bioRxiv

    Severe acute respiratory syndrome MESHD (SARS) and novel coronavirus disease MESHD ( COVID-19 MESHD) are caused by two closely related beta-coronaviruses, SARS-CoV and SARS-CoV-2 MESHD, respectively. The envelopes surrounding these viruses are decorated with spike proteins, whose receptor binding domains (RBDs) initiate invasion by binding to the human angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC). Subtle changes at the interface with ACE2 HGNC seem to be responsible for the enhanced affinity for the receptor of the SARS-CoV-2 RBD compared to SARS-CoV RBD MESHD. Here, we use Elastic Network Models (ENMs) to study the response of the viral RBDs and ACE2 HGNC upon dissassembly of the complexes. We identify a dominant detachment mode, in which the RBD rotates away from the surface of ACE2 HGNC, while the receptor undergoes a conformational transition which stretches the active-site cleft. Using the Structural Perturbation Method, we determine the network of residues, referred to as the Allostery Wiring Diagram (AWD), which drives the large-scale motion activated by the detachment of the complex. The AWD for SARS-CoV and SARS-CoV-2 MESHD are remarkably similar, showing a network that spans the interface of the complex and reaches the active site of ACE2 HGNC, thus establishing an allosteric connection between RBD binding and receptor catalytic function. Informed in part by the AWD, we used Molecular Dynamics simulations to probe the effect of interfacial mutations in which SARS-CoV-2 residues are replaced by their SARS-CoV counterparts. We focused on a conserved glycine (G502 in SARS-CoV-2, G488 in SARS-CoV MESHD) because it belongs to a region that initiates the dissociation of the complex along the dominant detachment mode, and is prominent in the AWD. Molecular Dynamics simulations of SARS-CoV-2 wild-type and G502P mutant show that the affinity for the human receptor of the mutant is drastically diminished. Our results suggest that in addition to residues that are in direct contact with the interface those involved in long range allosteric communication are also a determinant of the stability of the RBD- ACE2 HGNC complex.

    Prospective mapping of viral mutations that escape antibodies SERO used to treat COVID-19 MESHD

    Authors: Tyler N. Starr; Allison J. Greaney; Amin Addetia; William H. Hannon; Adam S. Dingens; Jesse D Bloom; Spyros Pournaras; Tom Burr; Yannis Duffourd; Helena Siemens; Chakib Alloui; Lin Song; Yvan Wenger; Alexandra Saitta; Morgane Macheret; Ewan W Smith; Philippe Menu; Marion Brayer; Lars M Steinmetz; Ali Si-Mohammed; Josiane Chuisseu; Richard Stevens; Pantelis Constantoulakis; Michela Sali; Gilbert Greub; Carsten Tiemann; Vicent Pelechano; Adrian Willig; Zhenyu Xu

    doi:10.1101/2020.11.30.405472 Date: 2020-12-01 Source: bioRxiv

    Antibodies SERO are becoming a frontline therapy for SARS-CoV-2, but the risk of viral evolutionary escape remains unclear. Here we map how all mutations to SARS-CoV-2's receptor-binding domain (RBD) affect binding by the antibodies SERO in Regeneron's REGN-COV2 cocktail and Eli Lilly's LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies SERO targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected MESHD patient treated with REGN-COV2, as well as in lab viral escape selections. Finally, the maps reveal that mutations escaping each individual antibody SERO are already present in circulating SARS-CoV-2 strains. Overall, these complete escape maps enable immediate interpretation of the consequences of mutations observed during viral surveillance.

    Neutrophil and monocyte dysfunctional effector response towards bacterial challenge in critically-ill COVID-19 MESHD patients

    Authors: Srikanth Mairpady Shambat; Alejandro Gomez-Mejia; Tiziano A. Schweizer; Markus Huemer; Chun-Chi Chang; Claudio Acevedo; Judith Bergada Pijuan; Clement Vulin; Nataliya Miroshnikova; Daniel A. Hofmanner; Pedro D. Wendel Garcia; Matthias P. Hilty; Philipp Karl Buehler; Reto A. Schuepbach; Silvio D Brugger; Annelies S. Zinkernagel; Philippe Menu; Marion Brayer; Lars M Steinmetz; Ali Si-Mohammed; Josiane Chuisseu; Richard Stevens; Pantelis Constantoulakis; Michela Sali; Gilbert Greub; Carsten Tiemann; Vicent Pelechano; Adrian Willig; Zhenyu Xu

    doi:10.1101/2020.12.01.406306 Date: 2020-12-01 Source: bioRxiv

    COVID-19 MESHD displays diverse disease severities and symptoms. Elevated inflammation MESHD mediated by hypercytokinemia induces a detrimental dysregulation of immune cells. However, there is limited understanding of how SARS-CoV-2 pathogenesis impedes innate immune signaling and function against secondary bacterial infections MESHD. We assessed the influence of COVID-19 MESHD hypercytokinemia on the functional responses of neutrophils and monocytes upon bacterial challenges from acute and corresponding recovery COVID-19 MESHD ICU patients. We show that severe hypercytokinemia in COVID-19 MESHD patients correlated with bacterial superinfections. Neutrophils and monocytes from acute COVID-19 MESHD patients showed severely impaired microbicidal capacity, reflected by abrogated ROS and MPO HGNC production as well as reduced NETs upon bacterial challenges. We observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes leading to a suppressive autocrine and paracrine signaling during bacterial challenges. Our data provide insights into the innate immune status of COVID-19 MESHD patients mediated by their hypercytokinemia and its transient effect on immune dysregulation upon subsequent bacterial infections

    Differential effects of antiseptic mouth rinses on SARS-CoV-2 infectivity in vitro

    Authors: Chuan Xu; Annie Wang; Eileen R Hoskin; Carla Cugini; Kenneth Markowitz; Theresa L Chang; Daniel H Fine; Clement Vulin; Nataliya Miroshnikova; Daniel A. Hofmanner; Pedro D. Wendel Garcia; Matthias P. Hilty; Philipp Karl Buehler; Reto A. Schuepbach; Silvio D Brugger; Annelies S. Zinkernagel; Philippe Menu; Marion Brayer; Lars M Steinmetz; Ali Si-Mohammed; Josiane Chuisseu; Richard Stevens; Pantelis Constantoulakis; Michela Sali; Gilbert Greub; Carsten Tiemann; Vicent Pelechano; Adrian Willig; Zhenyu Xu

    doi:10.1101/2020.12.01.405662 Date: 2020-12-01 Source: bioRxiv

    SARS-CoV-2 is detectable in saliva from asymptomatic TRANS individuals, suggesting the potential necessity for the use of mouth rinses to suppress viral load to reduce virus spread. Published studies on anti-SARS-CoV-2 activities of antiseptics determined by virus-induced cytotoxic effects cannot exclude antiseptic-associated cytotoxicity MESHD. Here, we determined the effect of commercially available mouth rinses and antiseptic povidone-iodine on the infectivity of pseudotyped SARS-CoV-2 virus. We first determined the effect of mouth rinses on cell viability to ensure that antiviral activity was not a consequence of mouth rinse-induced cytotoxicity MESHD. Colgate Peroxyl (hydrogen peroxide) exhibited the most cytotoxicity MESHD, followed by povidone-iodine-10% solution, chlorhexidine gluconate-0.12% (CHG), and Listerine (essential oils and alcohol). Analysis of the anti-viral activity of mouth rinses at non-cytotoxic concentrations showed that 1.5% (v/v) diluted CHG was a potent inhibitor when present in cells during infection, but the potency was reduced when CHG was removed after viral attachment, suggesting that the prolonged effect of mouth rinses on cells impacts the anti-viral activity. To minimalize mouth rinse-associated cytotoxicity MESHD, we pelleted treated-viruses to remove most of the mouth rinse prior to infection of cells. Colgate Peroxyl or povidone-iodine at 5% (v/v) completely blocked the viral infectivity. Listerine or CHG at 5% (v/v) had a moderate suppressive effect on the virus, and 50% (v/v) Listerine or CHG blocked the viral infectivity completely. Prolonged incubation of virus with mouth rinses was not required to block viral infectivity. Our results indicate that mouth rinses can significantly reduce virus infectivity, suggesting their potential use to reduce SARS-CoV-2 spread.

    A pomegranate peel extract as inhibitor of SARS-CoV-2 Spike binding to human ACE2 HGNC (in vitro): a promising source of novel antiviral drugs

    Authors: Annalisa Tito; Antonio Colantuono; Luciano Pirone; Emilia Maria Pedone; Daniela Intartaglia; Giuliana Giamundo; Ivan Conte; Paola Vitaglione; Fabio Apone; Daniel A. Hofmanner; Pedro D. Wendel Garcia; Matthias P. Hilty; Philipp Karl Buehler; Reto A. Schuepbach; Silvio D Brugger; Annelies S. Zinkernagel; Philippe Menu; Marion Brayer; Lars M Steinmetz; Ali Si-Mohammed; Josiane Chuisseu; Richard Stevens; Pantelis Constantoulakis; Michela Sali; Gilbert Greub; Carsten Tiemann; Vicent Pelechano; Adrian Willig; Zhenyu Xu

    doi:10.1101/2020.12.01.406116 Date: 2020-12-01 Source: bioRxiv

    Plant extracts are rich in bioactive compounds, such as polyphenols, sesquiterpenes and triterpenes, with potential antiviral activities. As the dramatic outbreak of the pandemic COVID-19 MESHD, caused by the SARS-CoV-2 virus, thousands of scientists are working tirelessly trying to understand the biology of this new virus and the disease pathophysiology, with the main goal to discover effective preventive treatments and therapeutic agents. Plant-derived secondary metabolites may play key roles in preventing and counteracting the rapid spread of SARS-CoV-2 infections MESHD by inhibiting the activity of several viral proteins, in particular those involved in the virus entry into the host cells and its replication. In this study, by using different in vitro approaches, we uncovered the role of a pomegranate peel extract in attenuating the interaction between the SARS-CoV-2 Spike glycoprotein and the human Angiotensin-Converting Enzyme 2 HGNC ( ACE2 HGNC) receptor, and in inhibiting the activity of the virus 3CL protease. Although further studies will be determinant to assess the efficacy of this extract in vivo, our results open up new promising opportunities to employ natural extracts for the development of effective and innovative therapies in the fight against SARS-CoV-2.

    Topoisomerase 1 inhibition therapy protects against SARS-CoV-2-induced inflammation MESHD and death MESHD in animal models.

    Authors: Jessica Sook Yuin Ho; Bobo Wing-Yee Mok; Laura Campisi; Tristan Jordan; Soner Yildiz; Natasha N Gaudreault; David A Meekins; Sabarish V Indran; Igor Morozov; Jessie D Trujillo; Yesai S Fstkchyan; Raveen Rathnasinghe; Zeyu Zhu; Simin Zheng; Nan Zhao; Kris White; Helen Ray-Jones; Valeriya Malysheva; Michiel J Thiecke; Siu-Ying Lau; Honglian Liu; Anna Junxia Zhang; Andrew Chak-Yiu Lee; Wen-Chun Liu; Teresa Aydillo; Betsaida S Melo; Ernesto Guccione; Robert Sebra; Elaine Shum; Jan Bakker; David A Kaufman; Andre Moreira; Mariano Carossino; Udeni B R Balasuriya; Minji Byun; Randy A Albrecht; Michael Schotsaert; Adolfo Garcia-Sastre; Sumit K Chanda; Anand D Jeyasekharan; Benjamin R TenOever; Mikhail Spivakov; Sven Heinz; Honglin Chen; Christopher Benner; Juergen A Richt; Ivan Marazzi

    doi:10.1101/2020.12.01.404483 Date: 2020-12-01 Source: bioRxiv

    The ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (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 MESHD induced by SARS-CoV-2. Therapeutic treatment with two doses of Topotecan (TPT), a FDA-approved Top1 inhibitor, suppresses infection-induced inflammation MESHD in hamsters. TPT treatment as late as four days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of Top1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection MESHD. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing Top1 inhibitors for COVID-19 MESHD in humans.

    Designed proteins assemble antibodies SERO into modular nanocages

    Authors: Robby Divine; Ha V. Dang; George Ueda; Jorge A. Fallas; Ivan Vulovic; William Sheffler; Shally Saini; Yan Ting Zhao; Infencia Xavier Raj; Peter A. Morawski; Madeleine F. Jennewein; Leah J. Homad; Yu-Hsin Wan; Marti R. Tooley; Franziska Seeger; Mitchell L. Fahning; Ali Etemadi; James Lazarovits; Alex Roederer; Alexandra C. Walls; Lance Stewart; Mohammadali Mazloomi; Neil P. King; Daniel J. Campbell; Andrew T. McGuire; Leonidas Stamatatos; Hannele Ruohola-Baker; Julie Mathieu; David Veesler; David Baker; David A Kaufman; Andre Moreira; Mariano Carossino; Udeni B R Balasuriya; Minji Byun; Randy A Albrecht; Michael Schotsaert; Adolfo Garcia-Sastre; Sumit K Chanda; Anand D Jeyasekharan; Benjamin R TenOever; Mikhail Spivakov; Sven Heinz; Honglin Chen; Christopher Benner; Juergen A Richt; Ivan Marazzi

    doi:10.1101/2020.12.01.406611 Date: 2020-12-01 Source: bioRxiv

    Antibodies SERO are widely used in biology and medicine, and there has been considerable interest in multivalent antibody SERO formats to increase binding avidity and enhance signaling pathway agonism. However, there are currently no general approaches for forming precisely oriented antibody SERO assemblies with controlled valency. We describe the computational design of two-component nanocages that overcome this limitation by uniting form and function. One structural component is any antibody SERO or Fc fusion and the second is a designed Fc-binding homo-oligomer that drives nanocage assembly. Structures of 8 antibody SERO nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies SERO per nanocage match the corresponding computational models. Antibody SERO nanocages targeting cell-surface receptors enhance signaling compared to free antibodies SERO or Fc-fusions in DR5-mediated apoptosis, Tie2 HGNC-mediated angiogenesis, CD40 HGNC activation, and T cell proliferation; nanocage assembly also increases SARS-CoV-2 pseudovirus neutralization by -SARS-CoV-2 monoclonal antibodies SERO and Fc-ACE2 fusion proteins. We anticipate that the ability to assemble arbitrary antibodies SERO without need for covalent modification into highly ordered assemblies with different geometries and valencies will have broad impact in biology and medicine.

    Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first six months of the COVID-19 pandemic MESHD

    Authors: Joseph H. Lubin; Christine Zardecki; Elliott M. Dolan; Changpeng Lu; Zhuofan Shen; Shuchismita Dutta; John D. Westbrook; Brian P. Hudson; David S. Goodsell; Jonathan K. Williams; Maria Voigt; Vidur Sarma; Lingjun Xie; Thejasvi Venkatachalam; Steven Arnold; Luz Helena Alfaro Alvarado; Kevin Catalfano; Aaliyah Khan; Erika McCarthy; Sophia Staggers; Brea Tinsley; Alan Trudeau; Jitendra Singh; Lindsey Whitmore; Helen Zheng; Matthew Benedek; Jenna Currier; Mark Dresel; Ashish Duvvuru; Britney Dyszel; Emily Fingar; Elizabeth M. Hennen; Michael Kirsch; Ali A. Khan; Charlotte Labrie-Cleary; Stephanie Laporte; Evan Lenkeit; Kailey Martin; Marilyn Orellana; Melanie Ortiz-Alvarez de la Campa; Isaac Paredes; Baleigh Wheeler; Allison Rupert; Andrew Sam; Katherine See; Santiago Soto Zapata; Paul A. Craig; Bonnie L. Hall; Jennifer Jiang; Julia R. Koeppe; Stephen A. Mills; Michael J. Pikaart; Rebecca Roberts; Yana Bromberg; J. Steen Hoyer; Siobain Duffy; Jay Tischfield; Francesc X. Ruiz; Eddy Arnold; Jean Baum; Jesse Sandberg; Grace Brannigan; Sagar D. Khare; Stephen K. Burley

    doi:10.1101/2020.12.01.406637 Date: 2020-12-01 Source: bioRxiv

    Three-dimensional structures of SARS-CoV-2 and other coronaviral proteins archived in the Protein Data Bank were used to analyze viral proteome evolution during the first six months of the COVID-19 pandemic MESHD. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48,000 viral proteome sequences showed how each one of the 29 viral study proteins have undergone amino acid changes. Structural models computed for every unique sequence variant revealed that most substitutions map to protein surfaces and boundary layers with a minority affecting hydrophobic cores. Conservative changes were observed more frequently in cores versus boundary layers/surfaces. Active sites and protein-protein interfaces showed modest numbers of substitutions. Energetics calculations showed that the impact of substitutions on the thermodynamic stability of the proteome follows a universal bi-Gaussian distribution. Detailed results are presented for six drug discovery targets and four structural proteins comprising the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and functional interfaces. Characterizing the evolution of the virus in three dimensions provides testable insights into viral protein function and should aid in structure-based drug discovery efforts as well as the prospective identification of amino acid substitutions with potential for drug resistance.

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MeSH Disease
HGNC Genes
Transmission
Seroprevalence


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