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Whiteite-(MnMnMn), Mn2+Mn2+Mn2+2Al2(PO4)4(OH)2⋅8H2O, is a new whiteite-subgroup member of the jahnsite group from the Foote Lithium Company mine, Kings Mountain district, Cleveland County, North Carolina, USA. It was found in small vugs of partially oxidised pegmatite minerals on the East dump of the mine, in association with eosphorite, hureaulite, fairfieldite, mangangordonite, whiteite-(CaMnMn) and jasonsmithite. It occurs as sugary aggregates of blade-like crystals up to 0.1 mm long and as epitaxial overgrowths on whiteite-(CaMnMn). The crystals are colourless to very pale brown, with a vitreous lustre and a white streak. The blades are flattened on {001} and elongated along [010], with poor cleavage on {001}. The calculated density is 2.82 g⋅cm–3. Optically it is biaxial (–) with α = 1.599(2), β = 1.605(2), γ = 1.609(2) (white light); 2V (calc.) = 78.2°, having no observable dispersion or pleochroism, and with orientation X = b. Electron microprobe analyses and structure refinement gave the empirical formula (Mn2+0.59Ca0.38Na0.03)Σ1.00Mn1.00(Mn2+1.04Fe3+0.58Fe2+0.23Zn0.16Mg0.08)Σ2.09Al2.04(PO4)3.89(OH)3.18(H2O)7.26. Whiteite-(MnMnMn) is monoclinic, P2/a, a = 15.024(3) Å, b = 6.9470(14) Å, c = 9.999(2) Å, β = 110.71(3)°, V = 976.2(4) Å3 and Z = 2. The crystal structure was refined using synchrotron single-crystal data to wRobs = 0.057 for 2014 reflections with I > 3σ(I). Site occupancy refinements confirm the ordering of dominant Mn in the X, M1 and M2 sites of the general jahnsite-group formula XM1(M2)2(M3)2(H2O)8(OH)2(PO4)4. A review of published crystallochemical data for jahnsite-group minerals shows a consistent chemical pressure effect in these minerals, manifested as a contraction of the unit-cell parameter, a, as the mean size of the X and M1 site cations increases. This is analogous to negative thermal expansion, but with increasing cation size, rather than heating, inducing octahedral rotations that result in an anisotropic contraction of the unit cell.

The general structural formula for the walentaite group is [((A1yA1’1–y), A2)(H2O)n][Bx(As2)2–x(As3)M1(M2)2(TO4)2(O,OH)7], based on heteropolyhedral layers of configuration [M1(M2)2(TO4)2(O,OH)6], with surface-coordinated species at the B, As2 and As3 sites, and with interlayer hydrated cation groups centred at the A sites. The group is divided into walentaite and halilsarpite subgroups based on T = P5+ and As5+, respectively. Alcantarillaite, (IMA2019-072), [Fe3+0.5□0.5(H2O)4][CaAs3+2(Fe3+2.5W6+0.5)(AsO4)2O7], is a new member of the walentaite group from the Alcantarilla wolframite mine, Belalcázar, Córdoba, Andalusia, Spain. It occurs most commonly as lemon-yellow fillings together with massive scorodite in fissures and cracks in quartz adjacent to löllingite. It is also found as tiny yellow rosettes lining vugs and as spheroids of ultrathin blades. It is associated with scorodite, pharmacosiderite, ferberite and schneiderhöhnite. Optically it is biaxial (–), with α = 1.703(calc), β = 1.800(5), γ = 1.850(5) and 2V = 68(1)° (white light). Dispersion is r > v, moderate. The optical orientation is X = a, Y = c and Z = b. The calculated density is 3.06 g cm–3. Electron microprobe analyses together with crystal structure refinement results gives the empirical formula [Fe3+0.52□0.48(H2O)4][(Ca0.44K0.11Na0.05Fe2+0.24□0.42)As3+1.83][Fe3+2.54Al0.03W6+0.43)((As0.65P0.35)O4)2O5.86(OH)1.14]. Alcantarillaite is orthorhombic, with an average structure described in Imma, and with a = 24.038(8) Å, b = 7.444(3) Å, c = 10.387(3) Å, V = 1858.6(11) Å3 and Z = 4. The structure (wRobs = 0.078 for 651 reflections to a resolution of 0.91 Å) differs most significantly from other walentaite-group members in having an interlayer A2 site occupied. Square-pyramidal polyhedra centred at the A2 sites form edge-shared dimers, (Fe3+)2O4(H2O)4. The dimers share vertices with TO4 anions in the layers on either side to form 8-sided channels along [010] occupied by H2O molecules.

Exceptionally large crystals of posnjakite, Cu4SO4(OH)6(H2O), formed during corrosion of a Swagelock(tm) Snubber copper gasket within the MX1 beamline at the ANSTO-Melbourne, Australian Synchrotron. The crystal structure was solved using synchrotron radiation and revealed a structure based upon [Cu4(OH)6(H2O)O] sheets, which contain Jahn–Teller-distorted Cu octa­hedra., Exceptionally large crystals of posnjakite, Cu4SO4(OH)6(H2O), formed during corrosion of a Swagelock(tm) Snubber copper gasket within the MX1 beamline at the ANSTO-Melbourne, Australian Synchrotron. The crystal structure was solved using synchrotron radiation to R 1 = 0.029 and revealed a structure based upon [Cu4(OH)6(H2O)O] sheets, which contain Jahn–Teller-distorted Cu octa­hedra. The sulfate tetra­hedra are bonded to one side of the sheet via corner sharing and linked to successive sheets via extensive hydrogen bonds. The sulfate tetra­hedra are split and rotated, which enables additional hydrogen bonds.

CD8+ T cells are crucial for anti-viral immunity; however, understanding T cell responses requires the identification of epitopes presented by human leukocyte antigens (HLA). To date, few SARS-CoV-2-specific CD8+ T cell epitopes have been described. Internal viral proteins are typically more conserved than surface proteins and are often the target of CD8+ T cells. Therefore, we have characterized eight peptides derived from the internal SARS-CoV-2 nucleocapsid protein predicted to bind HLA-A∗02:01, the most common HLA molecule in the global population. We determined not all peptides could form a complex with HLA-A∗02:01, and the six crystal structures determined revealed that some peptides adopted a mobile conformation. We therefore provide a molecular understanding of SARS-CoV-2 CD8+ T cell epitopes. Furthermore, we show that there is limited pre-existing CD8+ T cell response toward these epitopes in unexposed individuals. Together, these data show that SARS-CoV-2 nucleocapsid might not contain potent epitopes restricted to HLA-A∗02:01., Graphical abstract, Immunology; structural biology; virology

Significant efforts are being made worldwide to understand the immune response to SARS-CoV-2, responsible for the COVID-19 pandemic, including the role of pre-existing T cell immunity. Understanding the mechanisms that promote cross-recognition by T cells induced by seasonal coronaviruses will be critical for future predictions on the role of pre-existing immunity in protection against severe disease. We demonstrate that the SARS-CoV-2 nucleocapsid (N) protein induces an immunodominant response in HLA-B7+ COVID-19-recovered individuals that is also readily detectable in unexposed donors. This immunodominant response is driven by a single N-encoded epitope that displays a high degree of conservation with the homologous region in circulating coronaviruses. We show that T cell-mediated cross-reactivity can be detected towards the circulating OC43/HKU-1 coronaviruses, but not the 229E or NL63 coronaviruses, due to different peptide conformations. This cross-reactivity is driven by private T cell receptor repertoires with a bias for TRBV27 and a long CDR3b loop in unexposed and COVID-19-recovered individuals. Together, our findings demonstrate the basis of pre-existing immunity to a conserved and highly immunogenic SARS-CoV-2 epitope driven by cross-reactive memory T cells, suggesting long-lived protective immunity. Funding: This work was supported by generous donations from the QIMR Berghofer COVID 19 appeal, and financial contributions from Monash University, Australian Nuclear Science and Technology Organisation (ANSTO, AISNE ECR grants), Australian Research Council (ARC), National Health and Medical Research Council (NHMRC), and the Medical Research Future Fund (MRFF). H.S. is supported by an Australian Government Research Training Program Scholarship, E.J.G. was supported by an NHMRC CJ Martin Fellowship (#1110429) and is supported by an Australian Research Council DECRA (DE210101479), K.R.S.is supported by an Australian Research Council DECRA (DE180100512), S.G. is supported by and NHMRC SRF (#1159272). Conflict of Interest: The authors declare no competing interests. Ethical Approval: This study was performed according to the principles of the Declaration of Helsinki.Ethics approval to undertake the research was obtained from the QIMR Berghofer Medical Research Institute Human Research Ethics Committee and Monash University Human Research Ethics Committee.

The data currently available on how the immune system recognises the SARS-CoV-2 virus is growing rapidly. While there are structures of some SARS-CoV-2 proteins in complex with antibodies, which helps us understand how the immune system is able to recognise this new virus, however, we lack data on how T cells are able to recognise this virus. T cells, especially the cytotoxic CD8+ T cells, are critical for viral recognition and clearance. Here we report the X-ray crystallography structure of a T cell receptor, shared among unrelated individuals (public TCR) in complex with a dominant spike-derived CD8+ T cell epitope (YLQ peptide). We show that YLQ activates a polyfunctional CD8+ T cell response in COVID-19 recovered patients. We detail the molecular basis for the shared TCR gene usage observed in HLA-A*02:01+ individuals, providing an understanding of TCR recognition towards a SARS-CoV-2 epitope. Interestingly, the YLQ peptide conformation did not change upon TCR binding, facilitating the high-affinity interaction observed.

The SARS‐CoV‐2 coronavirus encodes an essential papain‐like protease domain as part of its non‐structural protein (nsp)‐3, namely SARS2 PLpro, that cleaves the viral polyprotein, but also removes ubiquitin‐like ISG15 protein modifications as well as, with lower activity, Lys48‐linked polyubiquitin. Structures of PLpro bound to ubiquitin and ISG15 reveal that the S1 ubiquitin‐binding site is responsible for high ISG15 activity, while the S2 binding site provides Lys48 chain specificity and cleavage efficiency. To identify PLpro inhibitors in a repurposing approach, screening of 3,727 unique approved drugs and clinical compounds against SARS2 PLpro identified no compounds that inhibited PLpro consistently or that could be validated in counterscreens. More promisingly, non‐covalent small molecule SARS PLpro inhibitors also target SARS2 PLpro, prevent self‐processing of nsp3 in cells and display high potency and excellent antiviral activity in a SARS‐CoV‐2 infection model., Crystal structure and biochemical analysis explains the specificity of SARS‐CoV‐2 PLpro for ISG15 and longer Lys48‐linked ubiquitin chains leading to the identification of inhibitors that show promising antiviral activity in a SARS‐CoV‐2 infection model.

Coronaviruses, including SARS-CoV-2, encode multifunctional proteases that are essential for viral replication and evasion of host innate immune mechanisms. The papain-like protease PLpro cleaves the viral polyprotein, and reverses inflammatory ubiquitin and anti-viral ubiquitin-like ISG15 protein modifications1,2. Drugs that target SARS-CoV-2 PLpro (hereafter, SARS2 PLpro) may hence be effective as treatments or prophylaxis for COVID-19, reducing viral load and reinstating innate immune responses3. We here characterise SARS2 PLpro in molecular and biochemical detail. SARS2 PLpro cleaves Lys48-linked polyubiquitin and ISG15 modifications with high activity. Structures of PLpro bound to ubiquitin and ISG15 reveal that the S1 ubiquitin binding site is responsible for high ISG15 activity, while the S2 binding site provides Lys48 chain specificity and cleavage efficiency. We further exploit two strategies to target PLpro. A repurposing approach, screening 3727 unique approved drugs and clinical compounds against SARS2 PLpro, identified no compounds that inhibited PLpro consistently or that could be validated in counterscreens. More promisingly, non-covalent small molecule SARS PLpro inhibitors were able to inhibit SARS2 PLpro with high potency and excellent antiviral activity in SARS-CoV-2 infection models.

A microfocus macromolecular crystallography beamline at the Australian Synchrotron is presented., MX2 is an in-vacuum undulator-based crystallography beamline at the 3 GeV Australian Synchrotron. The beamline delivers hard X-rays in the energy range 4.8–21 keV to a focal spot of 22 × 12 µm FWHM (H × V). At 13 keV the flux at the sample is 3.4 × 1012 photons s−1. The beamline endstation allows robotic handling of cryogenic samples via an updated SSRL SAM robot. This beamline is ideal for weakly diffracting hard-to-crystallize proteins, virus particles, protein assemblies and nucleic acids as well as smaller molecules such as inorganic catalysts and organic drug molecules. The beamline is now mature and has enjoyed a full user program for the last nine years. This paper describes the beamline status, plans for its future and some recent scientific highlights.