Corpus overview


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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (1492)

ProteinN (428)

NSP5 (315)

ComplexRdRp (187)

ProteinE (102)


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SARS-CoV-2 Proteins
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    Characterising contact in disease outbreaks via a network model of spatial-temporal proximity

    Authors: Ashleigh C Myall; Robert L Peach; Yu Wan; Siddharth Mookerjee; Elita Jauneikaite; Frankie Bolt; James Richard Price; Frances Davies; Andrea Yeong Wiesse; Alison Holmes; Mauricio Barahona

    doi:10.1101/2021.04.07.21254497 Date: 2021-04-09 Source: medRxiv

    Contact tracing is a key tool in epidemiology to identify and control outbreaks of infectious diseases MESHD. Existing contact tracing methodologies produce contact maps of individuals based on a binary definition of contact which can be hampered by missing data and indirect contacts. Here, we present our Spatial-temporal Epidemiological Proximity (StEP) model to recover contact maps in disease outbreaks based on movement data. The StEP model accounts for imperfect data by considering probabilistic contacts between individuals based on spatial-temporal proximity of their movement trajectories, creating a robust movement network despite possible missing data and unseen transmission routes. We showcase the potential of StEP for contact tracing with outbreaks of multidrug-resistant bacteria and COVID-19 MESHD in a large hospital group in London, UK. In addition to the core structure of contacts that can be recovered using traditional methods of contact tracing, the StEP model reveals missing contacts that connect seemingly separate outbreaks. Comparison with genomic data further confirmed that these additional contacts indeed improve characterisation of disease transmission and so highlights how the StEP framework can inform effective strategies of infection control and prevention.

    Social, demographic and behavioural determinants of SARS-CoV-2 infection MESHD: A case-control study carried out during mass community testing of asymptomatic individuals in South Wales, December 2020

    Authors: Daniel Rhys Thomas; Laia Fina; James Adamson; Clare Sawyer; Angela Jones; Kelechi Nnoaham; Alicia Barrasa; Giri Shankar; Christopher Williams

    doi:10.1101/2021.04.06.21253465 Date: 2021-04-09 Source: medRxiv

    Background Between 21 November and 22 December 2020, a SARS-CoV-2 community testing pilot took place in the South Wales Valleys. Lateral flow tests were offered to all people aged over 10 years living, studying or working in the area. Methods We conducted a case-control study in adults taking part in the pilot using an anonymous online questionnaire. Social, demographic and behavioural factors were compared in people with a positive test (cases) and a sample of negatives (controls). Population attributable fractions (PAF) were calculated for factors with significantly increased odds following multivariate analysis. Results A total of 199 cases and 2,621 controls were recruited by SMS HGNC (response rates: 27.1% and 37.6% respectively). Following adjustment, cases were more likely to work in the hospitality sector (aOR: 3.39, 95% CI: 1.43-8.03), social care (aOR: 2.63, 95% CI: 1.22-5.67) or healthcare (aOR: 2.31, 95% CI: 1.29-4.13), live with someone self-isolating due to contact with a case (aOR: 3.07, 95% CI: 2.03-4.62), visit a pub (aOR: 2.87, 95% CI: 1.11-7.37), and smoke or vape (aOR: 1.54, 95% CI: 1.02-2.32). In this community, and at this point in the epidemic, reducing transmission from a household contact who is self-isolating would have the biggest public health impact (PAF: 0.2). Conclusion Infection prevention and control should be strengthened to help reduce household transmission. As restrictions on social mixing are relaxed, hospitality venues will become of greater public health importance, and those working in this sector should be adequately protected. Smoking or vaping may be an important modifiable risk factor.

    Identifiability and Predictability of Integer- and Fractional-Order Epidemiological Models Using Physics-Informed Neural Networks

    Authors: Ehsan Kharazmi; Min Cai; Xiaoning Zheng; Guang Lin; George Em Karniadakis

    doi:10.1101/2021.04.05.21254919 Date: 2021-04-09 Source: medRxiv

    We analyze a plurality of epidemiological models through the lens of physics-informed neural networks (PINNs) that enable us to identify multiple time-dependent parameters and to discover new data-driven fractional differential operators. In particular, we consider several variations of the classical susceptible-infectious-removed (SIR) model by introducing more compartments and delay in the dynamics described by integer-order, fractional-order, and time-delay models. We report the results for the spread of COVID-19 MESHD in New York City, Rhode Island and Michigan states, and Italy, by simultaneously inferring the unknown parameters and the unobserved dynamics. For integer-order and time-delay models, we fit the available data by identifying time-dependent parameters, which are represented by neural networks (NNs). In contrast, for fractional differential models, we fit the data by determining different time-dependent derivative orders for each compartment, which we represent by NNs. We investigate the identifiability of these unknown functions for different datasets, and quantify the uncertainty associated with NNs and with control measures in forecasting the pandemic.

    COVID-19 MESHD vaccination acceptability in the UK at the start of the vaccination programme: a nationally representative cross-sectional survey (CoVAccS wave 2)

    Authors: Susan Mary Sherman; Julius Sim; Megan Cutts; Hannah Dasch; Richard Amlot; James Rubin; Nick Sevdalis; Louise E. Smith

    doi:10.1101/2021.04.06.21254973 Date: 2021-04-08 Source: medRxiv

    Aim: To investigate factors associated with intention to have the COVID-19 MESHD vaccination following initiation of the UK national vaccination programme. Methods: 1,500 adults completed an online cross-sectional survey (13th to 15th January 2021). Linear regression analyses were used to investigate associations between intention to be vaccinated for COVID-19 MESHD and sociodemographic factors, previous influenza vaccination, attitudes and beliefs about COVID-19 MESHD, attitudes and beliefs about COVID-19 MESHD vaccination and vaccination in general. Participants main reasons for likely vaccination uptake/decline were also solicited. Results: 73.5% of participants (95% CI 71.2%, 75.7%) reported being likely to be vaccinated against COVID-19 MESHD, 17.3% were unsure (95% CI 15.4%, 19.3%), and 9.3% (95% CI 7.9%, 10.8%) reported being unlikely to be vaccinated. The full regression model explained 69.8% of the variance in intention. Intention was associated with having been/intending to be vaccinated for influenza last winter/this winter, and with stronger beliefs about social acceptability of a COVID-19 MESHD vaccine; the need for vaccination; adequacy of information about the vaccine; and weaker beliefs that the vaccine is unsafe. Beliefs that only those at serious risk of illness should be vaccinated and that the vaccines are just a means for manufacturers to make money were negatively associated with vaccination intention. Conclusions: Most participants reported being likely to get the COVID-19 MESHD vaccination. COVID-19 MESHD vaccination attitudes and beliefs are a crucial factor underpinning vaccine intention. Continued engagement with the public with a focus on the importance and safety of vaccination is recommended.

    SARS-CoV-2 infection MESHD in the Syrian hamster model causes inflammation MESHD as well as type I interferon dysregulation MESHD in both respiratory and non-respiratory tissues including the heart and kidney

    Authors: Magen Francis; Una Goncin; Andrea Kroeker; Cynthia Swan; Robyn Ralph; Yao Lu; Athema Etzioni; Darryl Falzarano; Volker Gerdts; Steve Machtaler; Jason Kindrachuk; Alyson Ann Kelvin

    doi:10.1101/2021.04.07.438843 Date: 2021-04-08 Source: bioRxiv

    COVID-19 MESHD ( coronavirus disease 2019 MESHD) caused SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection MESHD is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 MESHD as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection MESHD in Syrian hamsters. We found significant increases in inflammatory cytokines ( IL-6 HGNC, IL-1beta HGNC, and TNF HGNC) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation MESHD in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of mycarditis and microthrombi while the kidney had tubular inflammation MESHD. These results give insight into the multiorgan disease experienced by people with COVID-19 MESHD and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).

    Examining changes in sleep duration associated with the onset of the COVID-19 pandemic MESHD: Who is sleeping and who is not?

    Authors: Salma Batool-Anwar; Rebecca Robbins; Shahmir H Ali; Ariadna Capasso; Joshua Foreman; Abbey M Jones; Yesim Tozan; Ralph J DiClemente; Stuart Quan

    doi:10.1101/2021.04.06.21254996 Date: 2021-04-08 Source: medRxiv

    Introduction The COVID-19 pandemic MESHD has resulted in social isolation and reports of insomnia MESHD. However, reports of changes in sleep duration and associated factors are few. Methods Data were from an online survey of adults recruited via social media that included a question asking whether the respondent slept less or more after the onset of the pandemic. Analyses determined the association between changes in sleep duration and self reported sociodemographic and occupational information; beliefs about COVID-19 MESHD; changes in sleep patterns; and responses pertaining to loneliness, anxiety MESHD, and depression MESHD. Results There were 5,175 respondents; 53.9% had a change in sleep duration. 17.1% slept less and 36.7% slept more. Sleeping more was related to greater education, being single/divorced/separated, unemployed or a student. Being retired, divorced/separated or a homemaker, and living in the Mountain or Central time zones were associated with less sleep. Beliefs that COVID-19 MESHD would result in personal adverse consequences was associated with both more and less sleep. However, the strongest associations with both more and less sleep were seen with depression MESHD, anxiety MESHD, and loneliness with adjusted odds ratios ranging from 1.92 (95% CI 1.67-2.21) for sleeping more and loneliness to 5.29 (95% CI 4.1-6.7) for sleeping less and anxiety MESHD. Conclusions Changes in sleep duration since the start of the COVID-19 pandemic MESHD were highly prevalent among social media users and were associated with several sociodemographic factors and beliefs that COVID-19 MESHD would have adverse personal impacts. However, the strongest associations occurred with worse mental health suggesting that improvements may occur with better sleep.

    Human pulmonary artery endothelial cells upregulate ACE2 HGNC expression in response to iron-regulatory elements: potential implications for SARS-CoV-2 infection MESHD of vascular endothelial cells.

    Authors: Quezia K Toe; Theo Issitt; Abdul Mahomed; Ioannis Panselinas; Fatma Almaghlouth; Anne Burke-Gaffney; Stephen John Wort; Gregory J Quinlan

    doi:10.1101/2021.04.08.437687 Date: 2021-04-08 Source: bioRxiv

    Emerging studies from the ongoing covid-19 pandemic MESHD have implicated vascular dysfunction MESHD and endotheliitis MESHD in many patients presenting with severe disease. However, there is limited evidence for the expression of ACE2 HGNC (the principal co-receptor for Sars-Cov-2 cellular attachment) in vascular endothelial cells which has prompted the suggestion that the virus does not infect these cell types. However, the studies presented here demonstrate enhanced expression of ACE2 HGNC at the level of both mRNA and protein, in human pulmonary artery endothelial cells (PAECs) challenged with either IL-6 HGNC or hepcidin HGNC. Notably elevated levels both these iron-regulatory elements have been described in Covid-19 MESHD patients with severe disease and are further associated with morbidity and mortality. Additionally, levels of both IL-6 HGNC and hepcidin HGNC are often elevated in the elderly and in chronic disease MESHD settings, these populations being at greater risk of adverse outcomes from Sars-Cov-2 infection MESHD. A role for IL-6 HGNC and hepcidin HGNC as modulators of ACE2 HGNC expression seems plausible, additional, studies are required to determine if viral infection MESHD can be demonstrated in PAECs challenged with either of these iron-regulatory elements.

    Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp12/7/8 RNA-dependent RNA Polymerase PROTEIN

    Authors: Rupert Beale; Agustina P Bertolin; Berta Canal; John FX Diffley; Lucy S Drury; Michael Howell; Jennifer Milligan; Viktor Posse; Rachel Ulferts; Florian Weissmann; Mary Wu; Jingkun Zeng

    doi:10.1101/2021.04.07.438807 Date: 2021-04-08 Source: bioRxiv

    The coronavirus disease 2019 MESHD ( COVID-19 MESHD) global pandemic has turned into the largest public health and economic crisis in recent history impacting virtually all sectors of society. There is a need for effective therapeutics to battle the ongoing pandemic. Repurposing existing drugs with known pharmacological safety profiles is a fast and cost-effective approach to identify novel treatments. The COVID-19 MESHD etiologic agent is the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), a single-stranded positive-sense RNA virus. Coronaviruses rely on the enzymatic activity of the replication-transcription complex (RTC) to multiply inside host cells. The RTC core catalytic component is the RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN) holoenzyme. The RdRp PROTEIN is one of the key druggable targets for CoVs due to its essential role in viral replication, high degree of sequence and structural conservation and the lack of homologs in human cells. Here, we have expressed, purified and biochemically characterised active SARS-CoV-2 RdRp complexes PROTEIN. We developed a novel fluorescence resonance energy transfer (FRET)-based strand displacement assay for monitoring SARS-CoV-2 RdRp PROTEIN activity suitable for a high-throughput format. As part of a larger research project to identify inhibitors for all the enzymatic activities encoded by SARS-CoV-2, we used this assay to screen a custom chemical library of over 5000 approved and investigational compounds for novel SARS-CoV-2 RdRp PROTEIN inhibitors. We identified 3 novel compounds (GSK-650394, C646 and BH3I-1) and confirmed suramin and suramin-like compounds as in vitro SARS-CoV-2 RdRp PROTEIN activity inhibitors. We also characterised the antiviral efficacy of these drugs in cell-based assays that we developed to monitor SARS-CoV-2 growth.

    Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp15 Endoribonuclease

    Authors: Rupert Beale; Agustina P Bertolin; Berta Canal; Tom D Deegan; John FX Diffley; Lucy S Drury; Ryo Fujisawa; Michael Howell; Karim Labib; Allison W McClure; Rachel Ulferts; Florian Weissmann; Mary Wu; Jingkun Zeng

    doi:10.1101/2021.04.07.438811 Date: 2021-04-08 Source: bioRxiv

    SARS-CoV-2 is responsible for COVID-19 MESHD, a human disease that has caused over 2 million deaths, stretched health systems to near-breaking point and endangered the economies of countries and families around the world. Antiviral treatments to combat COVID-19 MESHD are currently lacking. Remdesivir, the only antiviral drug approved for the treatment of COVID-19 MESHD, can affect disease severity, but better treatments are needed. SARS-CoV-2 encodes 16 non-structural proteins (nsp) that possess different enzymatic activities with important roles in viral genome replication, transcription and host immune evasion. One key aspect of host immune evasion is performed by the uridine-directed endoribonuclease activity of nsp15. Here we describe the expression and purification of nsp15 recombinant protein. We have developed biochemical assays to follow its activity, and we have found evidence for allosteric behaviour. We screened a custom chemical library of over 5000 compounds to identify nsp15 endoribonuclease inhibitors, and we identified and validated NSC95397 as an inhibitor of nsp15 endoribonuclease in vitro. Although NSC95397 did not inhibit SARS-CoV-2 growth in VERO E6 cells, further studies will be required to determine the effect of nsp15 inhibition on host immune evasion.

    Identification of SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of the nsp14 RNA Cap Methyltransferase

    Authors: Clovis Basier; Souradeep Basu; Rupert Beale; Berta Canal; Victoria H Cowling; Joseph F Curran; Tom D Deegan; John FX Diffley; Lucy S Drury; Ryo Fujisawa; Michael Howell; Karim Labib; Chew Theng Lim; Tiffany Mak; Allison W McClure; Emma Roberts; Kang Wei Tan; Rachel Ulferts; Florian Weissmann; Mary Wu; Theresa U Zeisner

    doi:10.1101/2021.04.07.438810 Date: 2021-04-08 Source: bioRxiv

    The COVID-19 pandemic MESHD has presented itself as one of the most critical public health challenges of the century, with SARS-CoV-2 being the third member of the Coronaviridae family to cause fatal disease MESHD in humans. There is currently only one antiviral compound, remdesivir, that can be used for the treatment of COVID-19 MESHD. In order to identify additional potential therapeutics, we investigated the enzymatic proteins encoded in the SARS-CoV-2 genome. In this study, we focussed on the viral RNA cap methyltransferases, which play a key role in enabling viral protein translation and facilitating viral escape from the immune system. We expressed and purified both the guanine- N7 methyltransferase nsp14 PROTEIN, and the nsp16 2-O-methyltransferase with its activating cofactor, nsp10. We performed an in vitro high-throughput screen for inhibitors of nsp14 using a custom compound library of over 5,000 pharmaceutical compounds that have previously been characterised in either clinical or basic research. We identified 4 compounds as potential inhibitors of nsp14, all of which also show antiviral capacity in a cell based model of SARS-CoV-2 infection MESHD. Three of the 4 compounds also exhibited synergistic effects on viral replication with remdesivir.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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