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SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this interaction presents an attractive possibility for suppressing SARS-CoV-2 replication. Here, we report the isolation and characterization of an alpaca-derived single domain antibody fragment, Ty1, that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike, directly preventing ACE2 engagement. Ty1 binds the RBD with high affinity, occluding ACE2. A cryo-electron microscopy structure of the bound complex at 2.9 Å resolution reveals that Ty1 binds to an epitope on the RBD accessible in both the ‘up’ and ‘down’ conformations, sterically hindering RBD-ACE2 binding. While fusion to an Fc domain renders Ty1 extremely potent, Ty1 neutralizes SARS-CoV-2 spike pseudovirus as a 12.8 kDa nanobody, which can be expressed in high quantities in bacteria, presenting opportunities for manufacturing at scale. Ty1 is therefore an excellent candidate as an intervention against COVID-19. Here, Hanke et al. immunize an alpaca with SARS-CoV-2 spike protein domains and identify a nanobody that binds the receptor binding domain of spike in both the up and down conformations and sterically hinders ACE2 engagement.

The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Therapeutic neutralizing antibodies constitute a key short-to-medium term approach to tackle COVID-19. However, traditional antibody production is hampered by long development times and costly production. Here, we report the rapid isolation and characterization of nanobodies from a synthetic library, known as sybodies (Sb), that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Several binders with low nanomolar affinities and efficient neutralization activity were identified of which Sb23 displayed high affinity and neutralized pseudovirus with an IC 50 of 0.6 µg/ml. A cryo-EM structure of the spike bound to Sb23 showed that Sb23 binds competitively in the ACE2 binding site. Furthermore, the cryo-EM reconstruction revealed an unusual conformation of the spike where two RBDs are in the ‘up’ ACE2-binding conformation. The combined approach represents an alternative, fast workflow to select binders with neutralizing activity against newly emerging viruses. Here, the authors isolate several nanobodies from a synthetic library that bind the receptor-binding domain (RBD) of SARS-CoV-2 spike protein (S) and neutralize S pseudotyped viruses. Cryo-EM structure of Spike with one nanobody and further biophysical analysis shows competition with ACE2 binding.

Antibodies binding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike have therapeutic promise, but emerging variants show the potential for virus escape. This emphasizes the need for therapeutic molecules with distinct and novel neutralization mechanisms. Here we describe the isolation of a nanobody that interacts simultaneously with two RBDs from different spike trimers of SARS-CoV-2, rapidly inducing the formation of spike trimer–dimers leading to the loss of their ability to attach to the host cell receptor, ACE2. We show that this nanobody potently neutralizes SARS-CoV-2, including the beta and delta variants, and cross-neutralizes SARS-CoV. Furthermore, we demonstrate the therapeutic potential of the nanobody against SARS-CoV-2 and the beta variant in a human ACE2 transgenic mouse model. This naturally elicited bispecific monomeric nanobody establishes an uncommon strategy for potent inactivation of viral antigens and represents a promising antiviral against emerging SARS-CoV-2 variants. Here, the authors isolate and characterize a bispecific monomeric nanobody that induces dimerization of SARS-CoV-2 spike trimers, neutralizes variants of concerns as well as SARS-CoV, and inhibits SARS-CoV-2 infection in mice.

We report on interfacial characteristics and chemistry of bonded Mg-Fe interfaces welded using friction stir assisted scribe technique (FaST). Two pairs of dissimilar joints: (AZ31-DP590) and (Pure Mg-DP590) were studied to shed light on joining mechanisms responsible for bonding of “immiscible” pairs of Mg and Fe. We present first direct experimental evidence of presence of oxide layer, Al segregation by atom probe tomography and nano steel grains close to interface by transmission electron microscopy study.

The continued evolution of SARS-CoV-2 underscores the need to understand qualitative aspects of the humoral immune response elicited by spike immunization. Here, we combine monoclonal antibody (mAb) isolation with deep B cell receptor (BCR) repertoire sequencing of rhesus macaques immunized with prefusion-stabilized spike glycoprotein. Longitudinal tracing of spike-sorted B cell lineages in multiple immune compartments demonstrates increasing somatic hypermutation and broad dissemination of vaccine-elicited B cells in draining and non-draining lymphoid compartments, including the bone marrow, spleen and, most notably, periaortic lymph nodes. Phylogenetic analysis of spike-specific monoclonal antibody lineages identified through deep repertoire sequencing delineates extensive intra-clonal diversification that shaped neutralizing activity. Structural analysis of the spike in complex with a broadly neutralizing mAb provides a molecular basis for the observed differences in neutralization breadth between clonally related antibodies. Our findings highlight that immunization leads to extensive intra-clonal B cell evolution where members of the same lineage can both retain the original epitope specificity and evolve to recognize additional spike variants not previously encountered. In this study, the authors investigate the dissemination and evolution of vaccination-induced antibody lineages in macaques and show that members of neutralizing lineages acquire different breadths allowing recognition of both previously encountered and not encountered viral variants.

Lattice distortions (LD) in 4H-silicon carbide (SiC) wafers were quantified using synchrotron X-ray rocking curve mapping (RCM), and were resolved into their two components of lattice strain (Δd/d) and lattice plane curvature (LPC) for 150 mm diameter wafers. The evolution of these LDs were investigated for three sequential substrates from the same boule, one of which was the substrate reference, and the other two had a 10 µm thick, 1 × 10 17 and 4 × 10 14  cm -3 n-type doped epitaxial layer. The lattice strain, Δd/d, was highest for the lowest doped wafer due to higher mismatch with the substrate wafer. After epitaxial layer growth, the LPC variation across the wafer increases by a factor of 2, irrespective of doping. The LPC maps indicate presence of a twist in the lattice planes that increases after epitaxial growth. The LPC component has higher influence on wafer shape change, which can reduce device yields. The lattice strain component predominantly affects the glide of basal plane dislocations (BPDs), thereby reducing device reliability. From analysis of peak widths, it was determined that threading dislocations in the top 6 microns of the wafer increase after epitaxial layer growth.

Friction stir welding has been attempted to evaluate joint strength of lap joint between aluminum sheet (AA6063) and zinc-coated steel (HIF-GA) sheet under different combination of rotational speed and traverse speed. The shear strength decreases significantly when rotational speed increases from 700 to 1,500 rpm at a traverse speed of 30 mm/min. At traverse speed of 50 mm/min, increasing rotational speed from 700 to 1,500 rpm, shear strength remains more or less the same. However, at a traverse speed of 100 mm/min, the shear strength increases significantly with increasing rotational speed from 700 to 1,500 rpm. Essentially, higher fracture load of the lap joint is obtained within a certain range of energy. The results have been correlated with the microstructural characteristics at the bond interface using energy dispersive X-ray spectroscopy, electron probe micro analyzer, and X-ray diffraction. The results show that characteristics of intermetallic compound formed at the interface derived from energy input takes predominating role towards lap joint of Al and coated steel. Furthermore, force and torque responses influenced by the processing parameters can be utilized as weld quality check.

This study focuses on the challenges with butt joining of 25 mm thick aluminum alloy 7175-T79. High-speed (150 mm/min) single-pass friction stir welding was employed as an effective technique for this purpose. The influence of quenching and cooling rate on critical performance level indicators such as joint strength and microstructure was investigated. A series of friction stir welding (FSW) trials, conducted both in air and with a trailing water spray using steel and composite backing plates (BP) revealed distinct hardness distribution in the nugget, heat-affected zone (HAZ), and HAZ minimum hardness. The influence of trailing water spray (TWS) on joint efficiency proves more significant than the impact of BP combinations, owing to their markedly different contributions to the quenching process. The ultimate tensile strength of TWS welds exhibited a notable 14% increase compared to the air welds. TWS also introduces multifaceted effects on FSW, including a reduction in processing temperature, an increase in X and Z forces, and decrease in Y force, and a narrowing of the HAZ. Lastly, the study employs digital image correlation (DIC)-based fracture mode analysis and grain size measurements, establishing correlations with the observed micro-hardness distribution.

The microstructure and mechanical properties of friction stir welded boron steel in butt joint configuration are experimentally studied. Two different friction stir welding (FSW) parameter combinations are used to successfully fabricate butt joints. Microstructural analysis exhibites that the stir zone (SZ) primarily consists of fine lath martensite, while the thermo-mechanically affected zone (TMAZ) comprises bainitic ferrite and granular bainite with a small amount of martensite. The presence of granular bainite in TMAZ suggests that alloying composition affects the phase transformation. The formation of recrystallized structures with lath martensites and high dislocation density in the SZ significantly enhance the hardness of the joints compared to that of the base metal. The results of the present study suggest that FSW can be used as a method for local hardening of structural components made of boron steels, without complicated heating and rapid cooling of a conventional hot stamping process.

A bimetallic ring component is forged by a friction stir assisted forging (FS-forging). A cylindrical bimetallic blank, magnesium AZ31 cylinder (Mg core) tightly fitted inside an aluminum 6061-T6 tube (Al skin), is used. In the FS-forging, the frictional heat and stirring of rotating tool forge the blank into a desired shape, while simultaneously generate a solid-state joint between the Mg core and the Al skin, without additional external heating, as confirmed by the microstructural analysis and mechanical tests. The microstructural analysis also shows that the characteristics of the solid-state joint can be different depending on the process parameters.