Investigation of protein-protein interactions and hotspot region on the NSP7-NSP8 binding site in NSP12 of SARS-CoV-2.

Background: The RNA-dependent RNA polymerase (RdRp) complex, essential in viral transcription and replication, is a key target for antiviral therapeutics. The core unit of RdRp comprises the nonstructural protein NSP12, with NSP7 and two copies of NSP8 (NSP81 and NSP82) binding to NSP12 to enhance its affinity for viral RNA and polymerase activity. Notably, the interfaces between these subunits are highly conserved, simplifying the design of molecules that can disrupt their interaction. Methods: We conducted a detailed quantum biochemical analysis to characterize the interactions within the NSP12-NSP7, NSP12-NSP81, and NSP12-NSP82 dimers. Our objective was to ascertain the contribution of individual amino acids to these protein-protein interactions, pinpointing hotspot regions crucial for complex stability. Results: The analysis revealed that the NSP12-NSP81 complex possessed the highest total interaction energy (TIE), with 14 pairs of residues demonstrating significant energetic contributions. In contrast, the NSP12-NSP7 complex exhibited substantial interactions in 8 residue pairs, while the NSP12-NSP82 complex had only one pair showing notable interaction. The study highlighted the importance of hydrogen bonds and π-alkyl interactions in maintaining these complexes. Intriguingly, introducing the RNA sequence with Remdesivir into the complex resulted in negligible alterations in both interaction energy and geometric configuration. Conclusion: Our comprehensive analysis of the RdRp complex at the protein-protein interface provides invaluable insights into interaction dynamics and energetics. These findings can guide the design of small molecules or peptide/peptidomimetic ligands to disrupt these critical interactions, offering a strategic pathway for developing effective antiviral drugs.

Magnetic behavior of a ferroferrimagnetic ternary alloy AB_{ρ}C_{1-ρ} with a selective site disorder: Case study of a mixed-spin Ising model on a honeycomb lattice.

Phase transitions, compensation phenomenon, and magnetization of a ferroferrimagnetic ternary alloy AB_{ρ}C_{1-ρ} composed of three different kinds of magnetic ions A, B, and C with the spin magnitudes 1/2, 1, and 3/2 are examined within the framework of a mixed-spin Ising model on a honeycomb lattice with a selective annealed site disorder on one of its two sublattices. It is supposed that the first sublattice of a bipartite honeycomb lattice is formed by the spin-1/2 magnetic ions, while the sites of the second sublattice are randomly occupied either by the spin-1 magnetic ions with a probability ρ or the spin-3/2 magnetic ions with a probability 1-ρ, both being subject to a uniaxial single-ion anisotropy. The model under investigation can be exactly mapped into an effective spin-1/2 Ising model on a triangular lattice through the generalized star-triangle transformation. For a specific concentration of the spin-1 (spin-3/2) magnetic ions, it is shown that the ferroferrimagnetic version of the studied model may display a compensation temperature at which the total magnetization vanishes below a critical temperature. The critical temperature strikingly may also become independent of the concentration of the randomly mixed spin-1 and spin-3/2 magnetic ions for a specific value of a uniaxial single-ion anisotropy. The spontaneous magnetic order may be notably restored at finite temperatures through the order-by-disorder mechanism above a disordered ground state, which results in an anomalous temperature dependence of the total magnetization with double reentrant phase transitions.

Universality and quasicritical exponents of one-dimensional models displaying a quasitransition at finite temperatures.

Quasicritical exponents of one-dimensional models displaying a quasitransition at finite temperatures are examined in detail. The quasitransition is characterized by intense sharp peaks in physical quantities such as specific heat and magnetic susceptibility, which are reminiscent of divergences accompanying a continuous (second-order) phase transition. The question whether these robust finite peaks follow some power law around the quasicritical temperature is addressed. Although there is no actual divergence of these quantities at a quasicritical temperature, a power-law behavior fits precisely both ascending as well as descending parts of the peaks in the vicinity but not too close to a quasicritical temperature. The specific values of the quasicritical exponents are rigorously calculated for a class of one-dimensional models (e.g., Ising-XYZ diamond chain, coupled spin-electron double-tetrahedral chain, Ising-XXZ two-leg ladder, and Ising-XXZ three-leg tube), whereas the same set of quasicritical exponents implies a certain "universality" of quasitransitions of one-dimensional models. Specifically, the values of the quasicritical exponents for one-dimensional models are: α=α^{'}=3 for the specific heat, γ=γ^{'}=3 for the susceptibility and ν=ν^{'}=1 for the correlation length.