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We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property–free knowledge base for future anticoronavirus drug discovery.more » « lessFree, publicly-accessible full text available November 10, 2024
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Abstract Carrion is long recognized as important to scavengers. How carrion may affect soil microbial biodiversity and ecosystem processes in natural systems is comparatively unknown, but is important for the intersection of vertebrate food webs, below‐ground processes and ecological heterogeneity.
We assessed in situ soil and plant responses to wolf‐killed mammal carrion in Yellowstone National Park, USA.
Bison and elk carcasses increased soil respiration and vegetation nutrient concentration and the carcasses contain altered bacterial and fungal communities compared to control plots. The ‘fingerprints’ of soil microbial taxa associated with bison compared to elk carcasses differed considerably and taxa are found dependent upon abiotic gradients and soil properties.
We found evidence that soil microbial community changes associated with carcasses may not be as generalizable as previously thought, which is important for a mechanistic understanding of the links between carrion and soil heterogeneity and potentially for applications in forensic science.
This work demonstrates the importance of carrion studies in natural systems. Our findings show that carrion creates distinct ecological patterns that contribute to both above‐ and below‐ground biological heterogeneity, linking carrion distribution dynamics with soil microbial biodiversity and ecosystem functions.
