Highlights d SARS-CoV-2 spike protein interacts with heparan sulfate and ACE2 through the RBD d Heparan sulfate promotes Spike-ACE2 interaction d SARS-CoV-2 infection is co-dependent on heparan sulfate and ACE2 d Heparin and non-anticoagulant derivatives block SARS-CoV-2 binding and infection
We present a comprehensive study of the evolution of the nematic electronic structure of FeSe using high resolution angle-resolved photoemission spectroscopy (ARPES), quantum oscillations in the normal state and elastoresistance measurements. Our high resolution ARPES allows us to track the Fermi surface deformation from four-fold to two-fold symmetry across the structural transition at ~87 K which is stabilized as a result of the dramatic splitting of bands associated with dxz and dyz character. The low temperature Fermi surface is that a compensated metal consisting of one hole and two electron bands and is fully determined by combining the knowledge from ARPES and quantum oscillations. A manifestation of the nematic state is the significant increase in the nematic susceptibility as approaching the structural transition that we detect from our elastoresistance measurements on FeSe. The dramatic changes in electronic structure cannot be explained by the small lattice effects and, in the absence of magnetic fluctuations above the structural transition, points clearly towards an electronically driven transition in FeSe stabilized by orbital-charge ordering.Comment: Latex, 8 pages, 4 figure
Cd3As2 is a candidate three-dimensional Dirac semi-metal which has exceedingly high mobility and nonsaturating linear magnetoresistance that may be relevant for future practical applications. We report magnetotransport and tunnel diode oscillation measurements on Cd3As2, in magnetic fields up to 65 T and temperatures between 1.5 K to 300 K. We find the non-saturating linear magnetoresistance persist up to 65 T and it is likely caused by disorder effects as it scales with the high mobility, rather than directly linked to Fermi surface changes even when approaching the quantum limit. From the observed quantum oscillations, we determine the bulk three-dimensional Fermi surface having signatures of Dirac behaviour with non-trivial Berry's phase shift, very light effective quasiparticle masses and clear deviations from the band-structure predictions. In very high fields we also detect signatures of large Zeeman spin-splitting (g ∼ 16).
We show that SARS-CoV-2 spike protein interacts with cell surface heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain. Docking studies suggest a putative heparin/heparan sulfate-binding site adjacent to the domain that binds to ACE2. In vitro, binding of ACE2 and heparin to spike protein ectodomains occurs independently and a ternary complex can be generated using heparin as a template. Contrary to studies with purified components, spike protein binding to heparan sulfate and ACE2 on cells occurs codependently. Unfractionated heparin, non-anticoagulant heparin, treatment with heparin lyases, and purified lung heparan sulfate potently block spike protein binding and infection by spike protein-pseudotyped virus and SARS-CoV-2 virus. These findings support a model for SARS-CoV-2 infection in which viral attachment and infection involves formation of a complex between heparan sulfate and ACE2. Manipulation of heparan sulfate or inhibition of viral adhesion by exogenous heparin may represent new therapeutic opportunities.
Magnetoresistivity ρxx and Hall resistivity ρxy in ultra high magnetic fields up to 88 T are measured down to 0.15 K to clarify the multiband electronic structure in high-quality single crystals of superconducting FeSe. At low temperatures and high fields we observe quantum oscillations in both resistivity and Hall effect, confirming the multiband Fermi surface with small volumes. We propose a novel approach to identify the sign of the charge carriers corresponding to a particular cyclotron orbit in a compensated metal from magnetotransport measurements. The observed significant differences in the relative amplitudes of the quantum oscillations between the ρxx and ρxy components, together with the positive sign of the high-field ρxy, reveal that the largest pocket should correspond to the hole band. The low-field magnetotransport data in the normal state suggest that, in addition to one hole and one almost compensated electron bands, the orthorhombic phase of FeSe exhibits an additional tiny electron pocket with a high mobility.
We present results from a survey of weak Mg ii absorbers in the VLT/UVES spectra of 81 QSOs obtained from the ESO archive. In this survey, we identified 112 weak Mg ii systems within the redshift interval 0:4 < z < 2:4 with 86% completeness down to a rest-frame equivalent width of W r (2796) ¼ 0:02 8, covering a cumulative redshift path length of ÁZ $ 77:3. From this sample, we estimate that the number of weak absorbers per unit redshift (dN/dz) increases from 1:06 AE 0:04 at z h i ¼ 1:9 to 1:76 AE 0:08 at z h i ¼ 1:2 and thereafter decreases to 1:51 AE 0:09 at z h i ¼ 0:9 and 1:06 AE 0:10 at z h i ¼ 0:6. Thus, we find evidence for an evolution in the population of weak Mg ii absorbers, with their number density peaking at z ¼ 1:2. We also determine the equivalent width distribution of weak systems at z h i ¼ 0:9 and z h i ¼ 1:9. At 0:4 < z < 1:4, there is evidence for a turnover from a power law of the form n(W r ) / W À1:04 r at W r (2796) < 0:1 8. This turnover is more extreme at 1:4 < z < 2:4, where the equivalent width distribution is close to an extrapolation of the exponential distribution function found for strong Mg ii absorbers. Based on these results, we discuss the possibility that some fraction of weak Mg ii absorbers, particularly single cloud systems, are related to satellite clouds surrounding strong Mg ii systems. These structures could also be analogs to Milky Way high-velocity clouds. In this context, the paucity of high-redshift weak Mg ii absorbers is caused by a lack of isolated clouds accreting onto galaxies during that epoch.
SARS-CoV-2 proteases Mpro and PLpro are promising targets for antiviral drug development. In this study, we present an antiviral screening strategy involving a novel in-cell protease assay, antiviral and biochemical activity assessments, as well as structural determinations for rapid identification of protease inhibitors with low cytotoxicity. We identified eight compounds with anti-SARS-CoV-2 activity from a library of 64 repurposed drugs and modeled at protease active sites by in silico docking. We demonstrate that Sitagliptin and Daclatasvir inhibit PLpro, and MG-101, Lycorine HCl, and Nelfinavir mesylate inhibit Mpro of SARS-CoV-2. The X-ray crystal structure of Mpro in complex with MG-101 shows a covalent bond formation between the inhibitor and the active site Cys145 residue indicating its mechanism of inhibition is by blocking the substrate binding at the active site. Thus, we provide methods for rapid and effective screening and development of inhibitors for blocking virus polyprotein processing as SARS-CoV-2 antivirals. Additionally, we show that the combined inhibition of Mpro and PLpro is more effective in inhibiting SARS-CoV-2 and the delta variant.
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