Corpus overview


MeSH Disease

Human Phenotype


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    A single-dose live-attenuated YF17D-vectored SARS-CoV2 vaccine candidate

    Authors: Lorena Sanchez Felipe; Thomas Vercruysse; Sapna Sharma; Ji Ma; Viktor Lemmens; Dominique van Looveren; Mahadesh Prasad Arkalagud Javarappa; Robbert Boudewijns; Bert Malengier-Devlies; Suzanne F. Kaptein; Laurens Liesenborghs; Carolien De Keyzer; Lindsey Bervoets; Madina Rasulova; Laura Seldeslachts; Sander Jansen; Michael Bright Yakass; Osbourne Quaye; Li-Hsin Li; Xin Zhang; Sebastiaan ter Horst; Niraj Mishra; Lotte Coelmont; Christopher Cawthorne; Koen Van Laere; Ghislain Opdenakker; Greetje Van de Velde; Birgit Weynand; Dirk E. Teuwen; Patrick Matthys; Johan Neyts; Hendrik Jan Thibaut; Kai Dallmeier

    doi:10.1101/2020.07.08.193045 Date: 2020-07-09 Source: bioRxiv

    The explosively expanding COVID-19 pandemic urges the development of safe, efficacious and fast-acting vaccines to quench the unrestrained spread of SARS-CoV-2. Several promising vaccine platforms, developed in recent years, are leveraged for a rapid emergency MESHD response to COVID-191. We employed the live-attenuated yellow fever MESHD fever HP 17D (YF17D) vaccine as a vector to express the prefusion form of the SARS-CoV-2 Spike antigen. In mice, the vaccine candidate, tentatively named YF-S0, induces high levels of SARS-CoV-2 neutralizing antibodies SERO and a favorable Th1 cell-mediated immune response. In a stringent hamster SARS-CoV-2 challenge model2, vaccine candidate YF-S0 prevents infection MESHD with SARS-CoV-2. Moreover, a single dose confers protection from lung disease MESHD in most vaccinated animals even within 10 days. These results warrant further development of YF-S0 as a potent SARS-CoV-2 vaccine candidate.

    Benefit-risk analysis of health benefits of routine childhood immunisation against the excess risk of SARS-CoV-2 infections MESHD during the Covid-19 pandemic in Africa

    Authors: Kaja Abbas; Simon R Procter; Kevin van Zandvoort; Andrew Clark; Sebastian Funk; - LSHTM CMMID Covid-19 Working Group; Tewodaj Mengistu; Dan Hogan; Emily Dansereau; Mark Jit; Stefan Flasche

    doi:10.1101/2020.05.19.20106278 Date: 2020-05-26 Source: medRxiv

    Background: National immunisation programmes globally are at risk of suspension due to the severe health system constraints and physical distancing measures in place to mitigate the ongoing COVID-19 pandemic. Our aim is to compare the health benefits of sustaining routine childhood immunisation in Africa against the risk of acquiring SARS-CoV-2 infections MESHD through visiting routine vaccination service delivery points. Methods: We used two scenarios to approximate the child TRANS deaths MESHD that may be caused by immunisation coverage reductions during COVID-19 outbreaks. First, we used previously reported country-specific child TRANS mortality impact estimates of childhood immunisation for diphtheria MESHD, tetanus MESHD, pertussis, hepatitis B MESHD hepatitis HP, Haemophilus influenzae type b, pneumococcal, rotavirus, measles MESHD, meningitis MESHD meningitis HP A, rubella MESHD, and yellow fever MESHD fever HP (DTP3, HepB3, Hib3, PCV3, RotaC, MCV1, MCV2, MenA, RCV, YFV) to approximate the future deaths MESHD averted before completing five years of age TRANS by routine childhood vaccination during a 6-month COVID-19 risk period without catch-up campaigns. Second, we analysed an alternative scenario that approximates the health benefits of sustaining routine childhood immunisation to only the child TRANS deaths MESHD averted from measles MESHD outbreaks during the COVID-19 risk period. The excess number of infections MESHD due to additional SARS-CoV-2 exposure during immunisation visits assumes that contact reducing interventions flatten the outbreak curve during the COVID-19 risk period, that 60% of the population will have been infected by the end of that period, that children TRANS can be infected by either vaccinators or during transport and that upon child TRANS infection MESHD the whole household would be infected. Country specific household age TRANS structure estimates and age TRANS dependent infection MESHD fatality rates are then applied to calculate the number of deaths MESHD attributable to the vaccination clinic visits. We present benefit-risk ratios for routine childhood immunisation alongside 95% uncertainty range estimates from probabilistic sensitivity SERO analysis. Findings: For every one excess COVID-19 death MESHD attributable to SARS-CoV-2 infections MESHD acquired during routine vaccination clinic visits, there could be 84 (14-267) deaths MESHD in children TRANS prevented by sustaining routine childhood immunisation in Africa. The benefit-risk ratio for the vaccinated children TRANS, siblings, parents TRANS or adult TRANS care-givers, and older adults TRANS in the households of vaccinated children TRANS are 85,000 (4,900 - 546,000), 75,000 (4,400 - 483,000), 769 (148 - 2,700), and 96 (14 - 307) respectively. In the alternative scenario that approximates the health benefits to only the child TRANS deaths MESHD averted from measles MESHD outbreaks, the benefit-risk ratio to the households of vaccinated children TRANS is 3 (0 - 10) under these highly conservative assumptions and if the risk to only the vaccinated children TRANS is considered, the benefit-risk ratio is 3,000 (182 - 21,000). Interpretation: Our analysis suggests that the health benefits of deaths MESHD prevented by sustaining routine childhood immunisation in Africa far outweighs the excess risk of COVID-19 deaths MESHD associated with vaccination clinic visits, especially for the vaccinated children TRANS. However, there are other factors that must be considered for strategic decision making to sustain routine childhood immunisation in African countries during the COVID-19 pandemic. These include logistical constraints of vaccine supply chain problems caused by the COVID-19 pandemic, reallocation of immunisation providers to other prioritised health services, healthcare staff shortages caused by SARS-CoV-2 infections MESHD among the staff, decreased demand for vaccination arising from community reluctance to visit vaccination clinics for fear of contracting SARS-CoV-2 infections MESHD, and infection MESHD infection risk TRANS infection risk TRANS risk to healthcare staff providing immunisation services as well as to their households and onward SARS-CoV-2 transmission TRANS into the wider community.

    Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19

    Authors: Arindam Banerjee; Rudra Prosad Goswami; Moumita Chatterjee

    doi:10.21203/ Date: 2020-04-28 Source: ResearchSquare

    Whenever some phenomenon can be represented as a graph or a network it seems pertinent to explore how much the mathematical properties of that network impact the phenomenon. In this study we explore the same philosophy in the context of immunology. Our objective was to assess the correlation of “size” (number of edges and minimum vertex cover) of the JAK/STAT network with treatment effect in rheumatoid arthritis MESHD rheumatoid arthritis HP (RA), phenotype of viral infection MESHD and effect of immunosuppressive agents on a system infected with the coronavirus. We extracted the JAK/STAT pathway from Kyoto Encyclopedia of Genes and Genomes (KEGG, hsa04630). The effects of the following drugs, and their combinations, commonly used in RA were tested: methotrexate, prednisolone, rituximab, tocilizumab, tofacitinib and baricitinib. Following viral systems were also tested for their ability to evade the JAK/STAT pathway: Measles MESHD, Influenza A, West Nile virus, Japanese B virus, Yellow Fever MESHD Fever HP virus, respiratory syncytial virus, Kaposi’s sarcoma MESHD sarcoma HP virus, Hepatitis B MESHD Hepatitis HP and C virus, cytomegalovirus, Hendra and Nipah virus and Coronavirus. Good correlation of edges and minimum vertex cover with clinical efficacy were observed (for edge, rho= -0.815, R2= 0.676, p=0.007, for vertex cover rho= -0.793, R2= 0.635, p=0.011). In the viral systems both edges and vertex cover were associated with acuteness of viral infections MESHD. In the JAK/STAT system already infected with coronavirus, maximum reduction in size was achieved with baricitinib. To conclude, algebraic and combinatorial invariant of a network may explain its biological behaviour. At least theoretically, baricitinib may be an attractive target for treatment of coronavirus infection MESHD.

    LY6E Restricts the Entry of Human Coronaviruses, including the currently pandemic SARS-CoV-2

    Authors: Xuesen Zhao; Shuangli Zheng; Danying Chen; Mei Zheng; Xinglin Li; Guoli Li; Hanxin Lin; Jinhong Chang; Hui Zeng; Ju-Tao Guo

    doi:10.1101/2020.04.02.021469 Date: 2020-04-05 Source: bioRxiv

    C3A is a sub-clone of human hepatoblastoma MESHD hepatoblastoma HP HepG2 cell line with the strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection MESHD than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an effort to search for the host cellular protein(s) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection MESHD, we found that ADAP2, GILT and LY6E, three cellular proteins with known activity of interfering virus entry, expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of HCoV-OC43. While overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection MESHD of HCoV-OC43, knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection MESHD. Moreover, we found that LY6E also efficiently restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFITM3 restriction of human coronavirus entry, but did not compromise the effect of LY6E on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E is a critical antiviral immune effector that controls CoV infection MESHD and pathogenesis via a distinct mechanism. ImportanceVirus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control by host innate and adaptive immune responses. In the last decade, several interferon inducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH and LY6E, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E was recently identified as host factors to facilitate the entry of several human pathogenic viruses, including human immunodeficiency HP virus, influenza A virus and yellow fever MESHD fever HP virus. Identification of LY6E as a potent restriction factor of coronaviruses expands the biological function of LY6E and sheds new light on the immunopathogenesis of human coronavirus infection MESHD.

    Topoisomerase III-beta is required for efficient replication of positive-sense RNA viruses

    Authors: K. Reddisiva Prasanth; Minato Hirano; W. Samuel Fagg; Eileen McAnarney; Shao Chan; Xuping Xie; Adam Hage; Colette Pietzsch; Alexander Bukreyev; Ricardo Rajsbaum; Pei-Yong Shi; Mark Bedford; Shelton Bradrick; Vineet D Menachery; Mariano A Garcia-Blanco

    doi:10.1101/2020.03.24.005900 Date: 2020-03-27 Source: bioRxiv

    Based on genome-scale loss-of-function screens we discovered that Topoisomerase III-{beta} (TOP3B), a human topoisomerase that acts on DNA and RNA, is required for yellow fever MESHD fever HP virus and dengue MESHD virus-2 replication. Remarkably, we found that TOP3B is required for efficient replication of all positive-sense-single stranded RNA viruses tested, including SARS-CoV-2. While there are no drugs that specifically inhibit this topoisomerase, we posit that TOP3B is an attractive anti-viral target.

    Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes

    Authors: Sara Cleemput; Wim Dumon; Vagner Fonseca; Wasim Abdool Karim; Marta Giovanetti; Luiz C. J. Alcantara; Koen Deforche; Tulio de Oliveira

    doi:10.1101/2020.01.31.928796 Date: 2020-02-02 Source: bioRxiv

    SummaryGenome Detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever MESHD Fever HP Virus in Brazil. Here, we present The Genome Detective Coronavirus Typing Tool that can accurately identify novel coronavirus (2019-nCoV) sequences isolated in China and around the world. The tool can accept up to 2,000 sequences per submission and the analysis of a new whole genome sequence will take approximately one minute. The tool has been tested and validated with hundreds of whole genomes from ten coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for 2019-nCoV. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines. AvailabilityAvailable online: * and Supplementary informationSupplementary data is available online.

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MeSH Disease
Human Phenotype

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