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We examined cardiac volumes (using echocardiography), intra-arterial blood pressure (BP), and intrathoracic pressure (ITP) in healthy males performing leg press exercise to failure at 95% of their maximum dynamic strength. Compared with preexercise, during the lifting phase of exercise, end-diastolic volume (EDV; 147 +/- 8 to 103 +/- 7 ml) and end-systolic volume (ESV; 54 +/- 5 to 27 +/- 4 ml) decreased (P < 0.05); heart rate (82 +/- 6 to 143 +/- 5 beats/min), systolic BP (160 +/- 6 to 270 +/- 21 Torr), diastolic BP (91 +/- 2 to 183 +/- 18 Torr), ITP (0.8 +/- 0.8 to 57.8 +/- 24 Torr), and peak systolic BP/ESV (SBP/ESV; 3.0 +/- 0.3 to 11.0 +/- 1.5 Torr/ml) increased (P < 0.05); and stroke volume decreased (94 +/- 3 to 77 +/- 4 ml; P > 0.05). Full knee extension was associated with most values returning to preexercise levels except for ESV (38 +/- 7 ml), heart rate (130 +/- 9 beats/min), and ITP (-12.5 +/- 2.1 Torr). During the lowering phase, significant decreases in EDV to 105 +/- 14 ml and ESV to 27 +/- 7 ml were observed with increases in systolic BP to 207 +/- 23 Torr, diastolic BP to 116 +/- 8 Torr, and SBP/ESV to 10.0 +/- 2.5 Torr/ml. Stroke volume decreased to 78 +/- 9 ml (P > 0.05). Thus rapid changes in cardiac volumes, contractility, and pressure occur during weight lifting that are related to different phases of the lift.

Herein we provide a living summary of the data generated during the COVID Moonshot project focused on the development of SARS-CoV-2 main protease (Mpro) inhibitors. Our approach uniquely combines crowdsourced medicinal chemistry insights with high throughput crystallography, exascale computational chemistry infrastructure for simulations, and machine learning in triaging designs and predicting synthetic routes. This manuscript describes our methodologies leading to both covalent and non-covalent inhibitors displaying protease IC50 values under 150 nM and viral inhibition under 5 uM in multiple different viral replication assays. Furthermore, we provide over 200 crystal structures of fragment-like and lead-like molecules in complex with the main protease. Over 1000 synthesized and ordered compounds are also reported with the corresponding activity in Mpro enzymatic assays using two different experimental setups. The data referenced in this document will be continually updated to reflect the current experimental progress of the COVID Moonshot project, and serves as a citable reference for ensuing publications. All of the generated data is open to other researchers who may find it of use.

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