6 research outputs found

    SARS-CoV-2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms

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    We modeled 3D structures of all SARS-CoV-2 proteins, generating 2,060 models that span 69% of the viral proteome and provide details not available elsewhere. We found that ˜6% of the proteome mimicked human proteins, while ˜7% was implicated in hijacking mechanisms that reverse post-translational modifications, block host translation, and disable host defenses; a further ˜29% self-assembled into heteromeric states that provided insight into how the viral replication and translation complex forms. To make these 3D models more accessible, we devised a structural coverage map, a novel visualization method to show what is-and is not-known about the 3D structure of the viral proteome. We integrated the coverage map into an accompanying online resource (https://aquaria.ws/covid) that can be used to find and explore models corresponding to the 79 structural states identified in this work. The resulting Aquaria-COVID resource helps scientists use emerging structural data to understand the mechanisms underlying coronavirus infection and draws attention to the 31% of the viral proteome that remains structurally unknown or dark

    SARS-CoV-2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms

    Get PDF
    Abstract We modeled 3D structures of all SARS‐CoV‐2 proteins, generating 2,060 models that span 69% of the viral proteome and provide details not available elsewhere. We found that ˜6% of the proteome mimicked human proteins, while ˜7% was implicated in hijacking mechanisms that reverse post‐translational modifications, block host translation, and disable host defenses; a further ˜29% self‐assembled into heteromeric states that provided insight into how the viral replication and translation complex forms. To make these 3D models more accessible, we devised a structural coverage map, a novel visualization method to show what is—and is not—known about the 3D structure of the viral proteome. We integrated the coverage map into an accompanying online resource (https://aquaria.ws/covid) that can be used to find and explore models corresponding to the 79 structural states identified in this work. The resulting Aquaria‐COVID resource helps scientists use emerging structural data to understand the mechanisms underlying coronavirus infection and draws attention to the 31% of the viral proteome that remains structurally unknown or dark

    One single large intramuscular dose of naloxone is effective and safe in suspected heroin poisoning

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    Objective: Naloxone is an established antidote for the treatment of heroin poisoning; however, dosing regimens vary widely, with a current trend towards small titrated intravenous dosing. This study aims to characterise naloxone use in the treatment of patients presenting with suspected heroin poisoning. Methods: This was a retrospective review of poisoned patients presenting to a clinical toxicology unit in Brisbane from January 2015 to December 2017. Patient demographics, clinical effects, naloxone dosing, observation periods and complications were extracted from the patient's medical records. Results: There were 117 presentations accounted for by 108 patients. Prehospital naloxone was provided to 57 (49%) patients, 46 of which received a standardised 1.6 mg i.m. dose. The remaining 60 (51%) patients received their first naloxone in hospital, with 58 (97%) receiving this by titrated i.v. doses. A subsequent naloxone infusion was required significantly more often in those treated with i.v. titrated naloxone compared to i.m. dose (27/69 [39%] vs 5/48 [10%], P = 0.0006). The need for parenteral sedation to manage acute behavioural disturbance following naloxone provision was rare (3/117 [3%]). Conclusions: In this retrospective observational study, a single large i.m. dose of naloxone reversed the toxicity of suspected heroin overdose in the majority of patients. In addition, patients were less likely to require repeated intermittent doses or naloxone infusion than those treated solely with i.v. naloxone. Further comparison in a prospective study is warranted to validate these observations in confirmed heroin overdose. Requirement for sedation secondary to acute behavioural disturbance was rare regardless of the route

    Abstracts of National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020

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    This book presents the abstracts of the papers presented to the Online National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020 (RDMPMC-2020) held on 26th and 27th August 2020 organized by the Department of Metallurgical and Materials Science in Association with the Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, India. Conference Title: National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020Conference Acronym: RDMPMC-2020Conference Date: 26–27 August 2020Conference Location: Online (Virtual Mode)Conference Organizer: Department of Metallurgical and Materials Engineering, National Institute of Technology JamshedpurCo-organizer: Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, IndiaConference Sponsor: TEQIP-
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