The Omicron (B.1.1.529) variant of SARS-CoV-2 binds to the hACE2 receptor more strongly and escapes the antibody response: Insights from structural and simulation data.

As SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) continues to inflict chaos globally, a new variant officially known as B.1.1.529 was reported in South Africa and was found to harbor 30 mutations in the spike protein. It is too early to speculate on transmission and hospitalizations. Hence, more analyses are required, particularly to connect the genomic patterns to the phenotypic attributes to reveal the binding differences and antibody response for this variant, which can then be used for therapeutic interventions. Given the urgency of the required analysis and data on the B.1.1.529 variant, we have performed a detailed investigation to provide an understanding of the impact of these novel mutations on the structure, function, and binding of RBD to hACE2 and mAb to the NTD of the spike protein. The differences in the binding pattern between the wild type and B.1.1.529 variant complexes revealed that the key substitutions Asn417, Ser446, Arg493, and Arg498 in the B.1.1.529 RBD caused additional interactions with hACE2 and the loss of key residues in the B.1.1.529 NTD resulted in decreased interactions with three CDR regions (1-3) in the mAb. Further investigation revealed that B.1.1.529 displayed a stable dynamic that follows a global stability trend. In addition, the dissociation constant (KD), hydrogen bonding analysis, and binding free energy calculations further validated the findings. Hydrogen bonding analysis demonstrated that significant hydrogen bonding reprogramming took place, which revealed key differences in the binding. The total binding free energy using MM/GBSA and MM/PBSA further validated the docking results and demonstrated significant variations in the binding. This study is the first to provide a basis for the higher infectivity of the new SARS-CoV-2 variants and provides a strong impetus for the development of novel drugs against them.

Study of p-SiC/n-GaN Hetero-Structural Double-Drift Region IMPATT Diode.

Nowadays, the immature p-GaN processes cannot meet the manufacturing requirements of GaN impact ionization avalanche transit time (IMPATT) diodes. Against this backdrop, the performance of wide-bandgap p-SiC/n-GaN heterojunction double-drift region (DDR) IMPATT diode is investigated in this paper for the first time. The direct-current (DC) steady-state, small-signal and large-signal characteristics are numerically simulated. The results show that compared with the conventional GaN single-drift region (SDR) IMPATT diode, the performance of the p-SiC/n-GaN DDR IMPATT proposed in this design, such as breakdown voltage, negative conductance, voltage modulation factor, radio frequency (RF) power and DC-RF conversion efficiency have been significantly improved. At the same time, the structure proposed in this design has a larger frequency bandwidth. Due to its greater potential in the RF power density, which is 1.97 MW/cm2 in this study, indicates that the p-SiC/n-GaN heterojunction provides new possibilities for the design and manufacture of IMPATT diode.