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.

Pathogenic thrombus formation accounts for the etiology of many serious conditions including myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism. Despite the development of numerous anticoagulants and antiplatelet agents, the mortality rate associated with these diseases remains high. In recent years, however, significant epidemiological evidence and clinical models have emerged to suggest that modulation of the glycoprotein VI (GPVI) platelet receptor could be harnessed as a novel antiplatelet strategy. As such, many peptidic agents have been described in the past decade, while more recent efforts have focused on the development of small molecule modulators. Herein the rationale for targeting GPVI is summarized and the published GPVI modulators are reviewed, with particular focus on small molecules. A qualitative pharmacophore hypothesis for small molecule ligands at GPVI is also presented.

) S U M M A R YPolyribosomes and ribosomes were isolated from vegetative Myxococcus xanthus FB and myxospores. The sedimentation coefficients of monoribosomes and ribosomal subunits were the same as those for equivalent particles from Escherichia coli. Conditions for the dissociation of the ribosomes and the unfolding of the subunits (in strong salt or very low concentrations of magnesium salts) differed from those required for analogous processes in E. coli. The stability of the 30 S subunits differed in preparations from vegetative M. xanthus and myxospores. Spermidine promoted the unfolding of the larger (50 S) subunit in low-magnesium buffer.Proteins were isolated from ribosomal subunits of Myxococcus xanthus, fractionated by polyacrylamide-gel electrophoresis and a catalogue was compiled. The proteins derived from 'native' subunits and from subunits partly unfolded in strong salt and from ribosomal subunits derived from vegetative cells and myxospores were compared. A difference in the profile of proteins from the 30 S subunits of myxospores and vegetative cells was found. The significance of these results is discussed in the light of the dissociation properties of the ribosomes and also the morphogenetic cycle of M . xanthus.

<div><div><div><p>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.<br></p></div></div></div>

S U M M A R YRNA was isolated from vegetative Myxococcus xanthus FB and myxospores. Organisms were labelled with [32P]orthophosphate during encystment and the metabolic stability of the radioactive RNA was followed by fractionating purified RNA from ' pulse-chased ' cultures by polyacrylamide gel electrophoresis. Much of the label was in heterodisperse (messenger-like) RNA but the stable RNA (present in the mature myxospores) was largely high-molecular weight ribosomal RNA and its precursors.The role of RNA synthesis in the morphogenetic cycle of Myxococcus xanthus is discussed in the light of these data and of the properties of the ribosomes and ribosomal proteins from this organism.