Structural biology of SARS-CoV-2 and implications for therapeutic development.
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ABSTRACT:
SUBMITTER: Yang H
PROVIDER: S-EPMC8447893 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:It has been said that COVID-19 is a generational challenge in many ways. But, at the same time, it becomes a catalyst for collective action, innovation, and discovery. Realizing the full potential of artificial intelligence (AI) for structure determination of unknown proteins and drug discovery are some of these innovations. Potential applications of AI include predicting the structure of the infectious proteins, identifying drugs that may be effective in targeting these proteins, and proposing new chemical compounds for further testing as potential drugs. AI and machine learning (ML) allow for rapid drug development including repurposing existing drugs. Algorithms were used to search for novel or approved antiviral drugs capable of inhibiting SARS-CoV-2. This paper presents a survey of AI and ML methods being used in various biochemistry of SARS-CoV-2, from structure to drug development, in the fight against the deadly COVID-19 pandemic. It is envisioned that this study will provide AI/ML researchers and the wider community an overview of the current status of AI applications particularly in structural biology, drug repurposing, and development, and motivate researchers in harnessing AI potentials in the fight against COVID-19.
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Project description:Interventions: Group 1: A qualitative interview study as well as a cross-sectional questionnaire survey is conducted with patients, oncologists and nurses working in the field of oncology (subproject 1). This is complemented by retrospective analysis of quantitative data derived from the registry of colon cancer centres (subproject 2) and data from the statutory health insurance (subproject 3).
Primary outcome(s): Aim: Assessment of ethical and psychosocial challenges in cancer care via semi-structured interviews with stakeholders (oncologists, nurses, patients) between January and July 2021. Assessment of psychosocial burden of oncologists, nurses and patients between February and July 2021 via questionnaires.
patients: Mini-SCL, EORTC QLQ-C30, NCCN Distress Thermometer, FACT-19
oncologists: PHQ-9, PHQ-15, GAD-7, Maslach Burnout Inventory, Moral Distress Thermometer, FACT-19, sociodemographic questionnaire
nurses: PHQ-9, PHQ-15, GAD-7, Maslach Burnout Inventory, Moral Distress Thermometer, FACT-19, BERNCA, sociodemographic questionnaire
Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: other
| 2439669 | ecrin-mdr-crc
Project description:BackgroundInterleukin-6 (IL-6) is elevated in SARS-CoV-2 infection. IL-6 regulates acute-phase proteins, such as alpha-1 antitrypsin (AAT), a key lung anti-protease. We investigated the protease-anti-protease balance in the circulation and pulmonary compartments in SARS-CoV-2 acute respiratory distress syndrome (ARDS) compared to non-SARS-CoV-2 ARDS (nsARDS) and the effects of tocilizumab (IL-6 receptor antagonist) on anti-protease defence in SARS-CoV-2 infection.MethodsLevels and activity of AAT and neutrophil elastase (NE) were measured in plasma, airway tissue and tracheal secretions (TA) of people with SARS-CoV-2 ARDS or nsARDS. AAT and IL-6 levels were evaluated in people with moderate SARS-CoV-2 infection who received standard of care +/- tocilizumab.FindingsAAT plasma levels doubled in SARS-CoV-2 ARDS. In lung parenchyma AAT levels were increased, as was the percentage of neutrophils involved in NET formation. A protease-anti-protease imbalance was detected in TA with active NE and no active AAT. The airway anti-protease, secretory leukoprotease inhibitor was decreased in SARS-CoV-2-infected lungs and cleaved in TA. In nsARDS, plasma AAT levels were elevated but TA samples had less AAT cleavage, with no detectable active NE in most samples. Induction of AAT in ARDS occurred mainly through IL-6. Tocilizumab down-regulated AAT during SARS-CoV-2 infection.InterpretationThere is a protease-anti-protease imbalance in the airways of SARS-CoV-2-ARDS patients. This imbalance is a target for anti-protease therapy.FundingNIH Serological Sciences Network, National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases.
| S-EPMC8861575 | biostudies-literature