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At least 163 records · Page 9

3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice

Pathogenic coronaviruses are a major threat to global public health, as exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound 1 day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses.

60 APPLIED LIFE SCIENCES↗

Seismic Monitoring at the Farnsworth CO2-EOR Field Using Time-Lapse Elastic-Waveform Inversion of 3D-3C VSP Data

During the Development Phase of the U.S. Southwest Regional Partnership on Carbon Sequestration, supercritical CO2 was continuously injected into the deep oil-bearing Morrow B formation of the Farnsworth Unit in Texas for Enhanced Oil Recovery (EOR). The project injected approximately 94 kilotons of CO2 to study geologic carbon storage during CO2-EOR. A three-dimensional (3D) surface seismic dataset was acquired in 2013 to characterize the subsurface structures of the Farnsworth site. Following this data acquisition, the baseline and three time-lapse three-dimensional three-component (3D-3C) vertical seismic profiling (VSP) data were acquired at a narrower surface area surrounding the CO2 injection and oil/gas production wells between 2014 and 2017 for monitoring CO2 injection and migration. With these VSP datasets, we inverted for subsurface velocity models to quantitatively monitor the CO2 plume within the Morrow B formation. We first built 1D initial P-wave (Vp) and S-wave (Vs) velocity models by upscaling the sonic logs. We improved the deep region of the Vp and Vs models by incorporating the deep part of a migration velocity model derived from the 3D surface seismic data. We improved the shallow region of 3D Vp and Vs models using 3D traveltime tomography of first arrivals of VSP downgoing waves. We further improved the 3D baseline velocity models using elastic-waveform inversion (EWI) of the 3D baseline VSP upgoing data. Our advanced EWI method employs alternative tomographic and conventional gradients and total-variation-based regularization to ensure the high-fidelity updates of the 3D baseline Vp and Vs models. We then sequentially applied our 3D EWI method to the three time-lapse datasets to invert for spatiotemporal changes of Vp and Vs in the reservoir. Our inversion results reveal the volumetric changes of the time-lapse Vp and Vs models and show the evolution of the CO2 plume from the CO2 injection well to the oil/gas production wells.

42 ENGINEERING↗

The Energetics of the Central Engine in the Powerful Quasar 3C 298

The compact steep-spectrum radio source 3C 298 (redshift of 1.44) has the largest 178 MHz luminosity in the Third Cambridge Revised Catalogue (3CR); its radio lobes are among the most luminous in the universe. The plasma state of the radio lobes is modeled with the aid of interferometric radio observations (in particular, the new Low Frequency Array observation and archival MERLIN data) and archival single-station data. It is estimated that the long-term time-averaged jet power required to fill these lobes with leptonic plasma is $\overline{Q}\,\approx 1.28\pm 0.51\times {10}^{47}\,\mathrm{erg}\,{{\rm{s}}}^{-1}$, rivaling the largest time-averaged jet powers from any quasar. Supporting this notion of extraordinary jet power is a 0.5–10 keV luminosity of ≈ 5.2 × 10 46 erg s –1 , comparable to luminous blazars, yet there is no other indication of strong relativistic beaming. We combine two new high signal-to-noise ratio optical spectroscopic observations from the Hobby-Eberly Telescope with archival Hubble Space Telescope, Two Micron All Sky Survey, and Galaxy Evolutionary Explorer data to compute a bolometric luminosity from the accretion flow of L bol ≈ 1.55 ± 0.15 × 10 47 erg s –1 . The ratio, $\overline{Q}/{L}_{\mathrm{bol}}\approx 1$, is the approximate upper limit for quasars. Characteristic of a large $\overline{Q}/{L}_{\mathrm{bol}}$, we find an extreme-ultraviolet (EUV) spectrum that is very steep (the "EUV deficit" of powerful radio quasars relative to radio-quiet quasars), and this weak ionizing continuum is likely a contributing factor to the relatively small equivalent widths of the broad emission lines in this quasar.

79 ASTRONOMY AND ASTROPHYSICS↗

Lunar Occultation of 3C 132

Diameter and position of radio source 3C 132 determined by lunar occultation, confirming identification with red galaxy

LUNAR OCCULTATION↗