X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (M^(pro)), which is essential for viral replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to M^(pro). In subsequent cell-based viral reduction assays, one peptidomimetic and six non-peptidic compounds showed antiviral activity at non-toxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2

Magmatism, serpentinization and life: Insights through drilling the Atlantis Massif (IODP Expedition 357)

IODP Expedition 357 used two seabed drills to core 17 shallow holes at 9 sites across Atlantis Massif ocean core complex (Mid-Atlantic Ridge 30°N). The goals of this expedition were to investigate serpentinization processes and microbial activity in the shallow subsurface of highly altered ultramafic and mafic sequences that have been uplifted to the seafloor along a major detachment fault zone. More than 57 m of core were recovered, with borehole penetration ranging from 1.3 to 16.4 meters below seafloor, and core recovery as high as 75% of total penetration in one borehole. The cores show highly heterogeneous rock types and alteration associated with changes in bulk rock chemistry that reflect multiple phases of magmatism, fluid-rock interaction and mass transfer within the detachment fault zone. Recovered ultramafic rocks are dominated by pervasively serpentinized harzburgite with intervals of serpentinized dunite and minor pyroxenite veins; gabbroic rocks occur as melt impregnations and veins. Dolerite intrusions and basaltic rocks represent the latest magmatic activity. The proportion of mafic rocks is volumetrically less than the amount of mafic rocks recovered previously by drilling the central dome of Atlantis Massif at IODP Site U1309. This suggests a different mode of melt accumulation in the mantle peridotites at the ridge-transform intersection and/or a tectonic transposition of rock types within a complex detachment fault zone. The cores revealed a high degree of serpentinization and metasomatic alteration dominated by talc-amphibole-chlorite overprinting. Metasomatism is most prevalent at contacts between ultramafic and mafic domains (gabbroic and/or doleritic intrusions) and points to channeled fluid flow and silica mobility during exhumation along the detachment fault. The presence of the mafic lenses within the serpentinites and their alteration to mechanically weak talc, serpentine and chlorite may also be critical in the development of the detachment fault zone and may aid in continued unroofing of the upper mantle peridotite/gabbro sequences. New technologies were also developed for the seabed drills to enable biogeochemical and microbiological characterization of the environment. An in situ sensor package and water sampling system recorded real-time variations in dissolved methane, oxygen, pH, oxidation reduction potential (Eh), and temperature and during drilling and sampled bottom water after drilling. Systematic excursions in these parameters together with elevated hydrogen and methane concentrations in post-drilling fluids provide evidence for active serpentinization at all sites. In addition, chemical tracers were delivered into the drilling fluids for contamination testing, and a borehole plug system was successfully deployed at some sites for future fluid sampling. A major achievement of IODP Expedition 357 was to obtain microbiological samples along a west–east profile, which will provide a better understanding of how microbial communities evolve as ultramafic and mafic rocks are altered and emplaced on the seafloor. Strict sampling handling protocols allowed for very low limits of microbial cell detection, and our results show that the Atlantis Massif subsurface contains a relatively low density of microbial life

Kristina G. Dunkel's Quick Files

The Quick Files feature was discontinued and it’s files were migrated into this Project on March 11, 2022. The file URL’s will still resolve properly, and the Quick Files logs are available in the Project’s Recent Activity

Ophicarbonates of the Feragen Ultramafic Body, central Norway

The carbonation of ultramafic rocks is a common alteration process in ophiolites and can occur in various settings. We provide the first detailed description of the carbonated peridotites (ophicarbonates) of the Feragen Ultramafic Body, central Norway, which have unusually variable compositions and microstructures. Lithologies range from pervasively carbonated serpentinites through carbonated serpentinite breccias to carbonated ultramafic conglomerates. Carbonate phases are Ca-carbonate, magnesite and dolomite. Some breccias are also cemented by coarsegrained brucite. This variability records strong variations in fluid chemistry and/or pressure and temperature conditions, both spatially and temporally. By analysing these altered ultramafic rocks using field relationships, optical microscopy, electron microprobe analysis and oxygen and carbon isotope compositions, we elucidate the history of the Feragen Ultramafic Body in more detail and emphasise the importance of deformation for the extent and type of alteration

Pristine microstructures in pseudotachylytes formed in dry lower crust, Lofoten, Norway

Feldspar-rich pseudotachylytes from the island of Moskenesøya, Lofoten, formed in dry granulites under lower crustal conditions during the Caledonian orogeny. The central parts of the pseudotachylytes, where the cooling rates were slowest, are characterized by microlites and spherulites of plagioclase and K-feldspar. K-feldspar surrounding plagioclase is consistent with crystallization from a melt during cooling instead of devitrification as the origin of the spherulites. Very thin (a few micrometres wide) injection veins, which experienced very rapid quenching, contain amorphous or cryptocrystalline material. The preservation of this material and of the fine-grained microstructures shows that, under fluid-absent conditions, recrystallization and reactions are slow and the original microstructures of the pseudotachylytes can be preserved. This article is part of a discussion meeting issue ‘Understanding earthquakes using the geological record’

Transfer of olivine crystallographic orientation through a cycle of serpentinisation and dehydration

Our ability to decipher the mechanisms behind metamorphic transformation processes depends in a major way on the extent to which crystallographic and microstructural information is transferred from one stage to another. Within the Leka Ophiolite Complex in the Central Norwegian Caledonides, prograde olivine veins that formed by dehydration of serpentinite veins in dunites exhibit a characteristic distribution of microstructures: The outer part of the veins comprises coarse-grained olivine that forms an unusual, brick-like microstructure. The inner part of the veins, surrounding a central fault, is composed of fine-grained olivine. Where the fault movement included a dilational component, optically clear, equant olivine occurs in the centre. Electron backscatter diffraction mapping reveals that the vein olivine has inherited its crystallographic preferred orientation (CPO) from the olivine in the porphyroclastic host rock; however, misorientation is weaker and associated to different rotation axes. We propose that prograde olivine grew epitaxially on relics of mantle olivine and thereby acquired its CPO. Growth towards pre-existing microfractures along which serpentinisation had occurred led to straight grain boundaries and a brick-like microstructure in the veins. When dehydration embrittlement induced slip, a strong strain localisation on discrete fault planes prevented distortion of the CPO due to cataclastic deformation; grain size reduction did not significantly modify the olivine CPO. This illustrates how a CPO can be preserved though an entire metamorphic cycle, including hydration, dehydration, and deformation processes, and that the CPO and the microstructures (e.g. grain shape) of one phase do not necessarily record the same event. © 2017 Springer Verla

Localized slip controlled by dehydration embrittlement of partly serpentinized dunites, Leka Ophiolite Complex, Norway

Dehydration of partly or completely serpentinized ultramafic rocks can increase the pore fluid pressure and induce brittle failure, a process referred to as dehydration embrittlement. However the extents of strain localization and unstable frictional sliding during deserpentinization are still under debate. In the layered ultramafic sections of the Leka Ophiolite Complex in the Central Norwegian Caledonides, prograde metamorphism of serpentinite veins led to local fluid production and to the growth of Mg-rich and coarse-grained olivine with abundant magnetite inclusions and δ18O values ‰ below the host rock. Embrittlement associated with the dehydration caused faulting along highly localized (<10 μm-wide) slip planes near the centers of the original serpentinite veins and pulverization of wall rock olivine. These features along with an earthquake-like size distribution of fault offsets suggest unstable frictional sliding rather than slower creep. Structural heterogeneities in the form of serpentinite veins clearly have first-order controls on strain localization and frictional sliding during dehydration. As most of the oceanic lithosphere is incompletely serpentinized, heterogeneities represented by a non-uniform distribution of serpentinite are common and may increase the likelihood that dehydration embrittlement triggers earthquakes

High transient stress in the lower crust: Evidence from dry pseudotachylytes in granulites, Lofoten Archipelago, northern Norway

Seismic activity below the standard seismogenic zone is difficult to investigate because the geological records of such earthquakes, pseudotachylytes, are typically reacted and/or deformed. Here, we describe unusually pristine pseudotachylytes in lower-crustal granulites from the Lofoten Archipelago, northern Norway. The pseudotachylytes have essentially the same mineralogical composition as their host (mainly plagioclase, alkali feldspar, orthopyroxene) and contain microstructures indicative of rapid cooling, i.e., feldspar microlites and spherulites and “cauliflower” garnets. Mylonites are absent, both in the wall rocks and among the pseudotachylyte clasts. The absence of features recording precursory ductile deformation rules out several commonly invoked mechanisms for triggering earthquakes in the lower crust, including thermal runaway, plastic instabilities, and downward propagation of seismic slip from the brittle to the ductile part of a fault. The anhydrous mineralogy of host and pseudotachylytes excludes dehydration-induced embrittlement. In the absence of such weakening mechanisms, stress levels in the lower crust must have been transiently high

Fragmentation of wall rock garnets during deep crustal earthquakes

Fractures and faults riddle the Earth’s crust on all scales, and the deformation associated with them is presumed to have had significant effects on its petrological and structural evolution. However, despite the abundance of directly observable earthquake activity, unequivocal evidence for seismic slip rates along ancient faults is rare and usually related to frictional melting and the formation of pseudotachylites. We report novel microstructures from garnet crystals in the immediate vicinity of seismic slip planes that transected lower crustal granulites during intermediate-depth earthquakes in the Bergen Arcs area, western Norway, some 420 million years ago. Seismic loading caused massive dislocation formations and fragmentation of wall rock garnets. Microfracturing and the injection of sulfide melts occurred during an early stage of loading. Subsequent dilation caused pervasive transport of fluids into the garnets along a network of microfractures, dislocations, and subgrain and grain boundaries, leading to the growth of abundant mineral inclusions inside the fragmented garnets. Recrystallization by grain boundary migration closed most of the pores and fractures generated by the seismic event. This wall rock alteration represents the initial stages of an earthquake-triggered metamorphic transformation process that ultimately led to reworking of the lower crust on a regional scale

Microstructural Records of Earthquakes in the Lower Crust and Associated Fluid-Driven Metamorphism in Plagioclase-Rich Granulites

Coseismic damage associated with earthquakes in the lower continental crust is accompanied by postseismic annealing and fluid‐mediated metamorphism that influence the physical and chemical development of the continental crust on regional scales. A transition from brittle deformation to crystal‐plastic recrystallization is a recurring characteristic of rocks affected by lower crustal earthquakes and is observed in plagioclase adjacent to pseudotachylytes in granulite facies anorthosites from the Bergen Arcs, western Norway. The microstructural and petrological records of this transition were investigated using electron microscopy, electron microprobe analysis, and electron backscatter diffraction analysis. Microfractures associated with mechanical twins are abundant within plagioclase and contain fine‐grained aggregates that formed by fragmentation with minor shear deformation. The presence of feather features, which are described for the first time in feldspar, suggests that fractures propagate at near the shear wave velocity into the wall rock of earthquake slip planes. Grain size insensitive recrystallization took place within the time frame of pseudotachylyte formation, forming high‐angle grain boundaries required for shear zone initiation. Fluid infiltration synfracture to postfracture facilitated the epitactic replacement of plagioclase by alkali feldspar and the nucleation of clinozoisite, kyanite, and quartz. The grain size reduction and crystallization associated with the microfractures create rheologically weak areas that have the potential to localize strain within the plagioclase‐rich lower crust. ©2018. American Geophysical Union. All Rights Reserved