Neuropeptides,New Ligands of SARS-CoV-2 Nucleoprotein,a Potential Link between Replication,Inflammation and Neurotransmission

This work identifies new ligands of the nucleoprotein N of SARS-CoV-2 by in silico screening, which used a new model of N, built from an Alphafold model refined by molecular dynamic simulations. The ligands were neuropeptides, such as substance P (1-7) and enkephalin, bound at a large site of the C-terminal or associated with the N-terminal β−sheet. The BA4 and BA5 Omicron variants of N also exhibited a large site as in wt N, and an increased flexibility of the BA5 variant, enabling substance P binding. The binding sites of some ligands deduced from modeling in wt N were assessed by mutation studies in surface plasmon resonance experiments. Dynamic light scattering showed that the ligands impeded RNA binding to N, which likely inhibited replication. We suggest that the physiological role of these neuropeptides in neurotransmission, pain and vasodilation for cholecystokinin and substance P could be altered by binding to N. We speculate that N may link between viral replication and multiple pathways leading to long COVID-19 symptoms. Therefore, N may constitute a “danger hub” that needs to be inhibited, even at high cost for the host. Antivirals targeted to N may therefore reduce the risk of brain fog and stroke, and improve patients’ health.     

Novel Polymer‐Bound Aminoalcohol Ligands for the Asymmetric Addition of Diethylzinc to Aldehydes

The synthesis of several novel polymer‐supported aziridine‐containing aminoalcohol chiral ligands has been accomplished, and the polymers have been used as ligands for the catalytic asymmetric addition of diethylzinc to benzaldehyde, giving up to 89% ee. Incorporation onto a polymer support prevents the variation of ee with time that is observed in reactions of one unsupported ligand, perhaps as a result of site isolation of the ligand within the polymer, preventing cooperative effects.     

Vortex lattice transitions in YNi2B2C

We have performed extensive small-angle neutron scattering (SANS) diffraction studies of the vortex lattice in single crystal YNi₂B₂C for B‖c. High-resolution SANS, combined with a field-oscillation vortex lattice preparation technique, allows us to separate Bragg scattered intensities from two orthogonal domains and accurately determine the unit cell angle, β. The data suggest that upon increasing field there is a finite transition width where both low- and high-field distorted hexagonal vortex lattice phases, mutually rotated by 45°, coexist. The smooth variation of diffracted intensity from each phase through the transition corresponds to a redistribution of populations between the two types of domains.     

Centred TVD schemes for hyperbolic conservation laws

New first- and high-order centred methods for conservation lawsare presented. Convenient TVD conditions for constructing centredTVD schemes are then formulated and some useful results areproved. Two families of centred TVD schemes are constructedand extended to nonlinear systems. Some numerical results arealso presented.     

Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus

There is an urgent need for specific antiviral treatments directed against SARS-CoV-2 to prevent the most severe forms of COVID-19. By drug repurposing, affordable therapeutics could be supplied worldwide in the present pandemic context. Targeting the nucleoprotein N of the SARS-CoV-2 coronavirus could be a strategy to impede viral replication and possibly other essential functions associated with viral N. The antiviral properties of naproxen, a non-steroidal anti-inflammatory drug (NSAID) that was previously demonstrated to be active against Influenza A virus, were evaluated against SARS-CoV-2. Intrinsic fluorescence spectroscopy, fluorescence anisotropy, and dynamic light scattering assays demonstrated naproxen binding to the nucleoprotein of SARS-Cov-2 as predicted by molecular modeling. Naproxen impeded recombinant N oligomerization and inhibited viral replication in infected cells. In VeroE6 cells and reconstituted human primary respiratory epithelium models of SARS-CoV-2 infection, naproxen specifically inhibited viral replication and protected the bronchial epithelia against SARS-CoV-2-induced damage. No inhibition of viral replication was observed with paracetamol or the COX-2 inhibitor celecoxib. Thus, among the NSAID tested, only naproxen combined antiviral and anti-inflammatory properties. Naproxen addition to the standard of care could be beneficial in a clinical setting, as tested in an ongoing clinical study.     

Vacuum moulding of a superplastic in two dimensions

A mathematical model is proposed for the process of vacuum superplasticforming. The model exploits the fact that in most industrialapplications the sheet aspect ratio (thickness/sheet width)is small. After an initial consideration of some of the moregeneral properties and the literature of superplastic materials,the elastic/plastic deformation of an internally-inflated thin-walledcylinder is examined. Plates of arbitrary geometry are thenconsidered. A quasisteady model in which the sheet moves througha sequence of steady states is developed. Some simplified closed-formsolutions are examined, but for general cases a system of nonlinearpartial differential equations must be solved numerically. Anefficient and accurate semi-explicit numerical scheme is proposedand a simplified stability analysis is presented; the methodis then used to compute properties of superplastic vacuum mouldedsheets in a number of practically motivated cases.     

The true potential energy curves for different states of SiO and SiS molecules

The true potential energy curves forX ¹ Σ ⁺, a³ π _r,A ¹ π,e ³ Σ ⁻,E ¹ Σ ⁺,c ³ π _i states of astrophysically important molecule SiO, whose spectra were observed in the sunspots, have been constructed using the method of Lakshman and Rao. Dissociation energy and ionization potential have been estimated as 65,350 cm⁻¹ and 92,854 cm⁻¹ respectively and found to be in good agreement with the values cited in literature. The true potential energy curves forX ¹ Σ ⁺,D ¹ π andE ¹ Σ ⁺ states of SiS molecule have been constructed by the same method and its dissociation energy in the ground state has been estimated using Hulburt-Hirschfelder potential function as 54,765 cm⁻¹ in good agreement with 53,250.9 cm⁻¹ given by Herzberg.     

Second-order Raman scattering in MgO

We have applied our recently formulated deformable-ion model, which encompasses both the shell model and the deformation-dipole model, to compute the lattice dynamics of MgO which is in very good overall agreement with the elastic constant, dielectric constant, and neutron scattering data. We use this lattice dynamics in the second-order Raman spectra calculations where the polarizability tensor constants are fitted to the experimental spectra. Our calculated spectra agree quite well with the experimental data.