Multiscale Modeling and Dynamic Mutational Profiling of Binding Energetics and Immune Escape for Class I Antibodies with SARS-CoV-2 Spike Protein: Dissecting Mechanisms of High Resistance to Viral Escape Against Emerging Variants.

The rapid evolution of SARS-CoV-2 has underscored the need for a detailed understanding of antibody binding mechanisms to combat immune evasion by emerging variants. In this study, we investigated the interactions between Class I neutralizing antibodies-BD55-1205, BD-604, OMI-42, P5S-1H1, and P5S-2B10-and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein using multiscale modeling, which combined molecular simulations with the ensemble-based mutational scanning of the binding interfaces and binding free energy computations. A central theme emerging from this work is that the unique binding strength and resilience to immune escape of the BD55-1205 antibody are determined by leveraging a broad epitope footprint and distributed hotspot architecture, additionally supported by backbone-mediated specific interactions, which are less sensitive to amino acid substitutions and together enable exceptional tolerance to mutational escape.

Dynamic mutational profiling of binding interactions and allosteric networks in conformational ensembles of the SARS-CoV-2 spike protein complexes with classes of antibodies targeting cryptic binding sites: confluence of binding and allostery determines molecular mechanisms and hotspots of immune escape.

The ongoing evolution of SARS-CoV-2 variants has underscored the need to understand not only the structural basis of antibody recognition but also the dynamic and allosteric mechanisms that could be the underlying contributors to their complex broad and escape-resistant neutralization activities. In this study, we employed a multi-scale approach integrating structural analysis, hierarchical molecular simulations, mutational scanning and network-based allosteric modeling to dissect how class 4 antibodies (represented by S2X35, 25F9, and SA55) and class 5 antibodies (represented by S2H97, WRAIR-2063 and WRAIR-2134) can modulate conformational behavior, binding energetics, allosteric interactions and immune escape patterns of the SARS-CoV-2 spike protein. Using hierarchical simulations of the antibody complexes with the spike protein and ensemble-based mutational scanning of binding interactions we showed that these antibodies through targeting conserved cryptic sites can exert allosteric effects that influence global conformational dynamics in the RBD functional regions.

Unique genetic signatures in HIV-1 subtype A1 and A1D recombinant envelope glycoprotein distinguish contemporary transmitted/founder viruses from historical strains in East Africa.

Introduction: The envelope glycoprotein (Env) of HIV-1 Transmitted/Founder (T/F) viruses in subtypes B and C carries distinct genetic signatures that enhance transmission fitness, augment infectivity and immune evasion. However, there is limited data on such signatures in T/F subtypes A1, D and A1D recombinants that predominate East Africa's HIV epidemic.

Methods: We used phylogenetically corrected approaches to detect distinct genetic signatures by comparing 44 contemporary HIV-1 T/F Envs with 229 historical Envs of the same subtype in East Africa.

"Predictors of Increased Mortality in Facial Trauma Patients Over 65".

Background: The overall rate of death in facial trauma patients is <1%; however, this figure increases significantly in the elderly, with estimates as high as 15 times greater than the general population. While the majority of facial fractures occur in young males, there is a dearth of literature regarding morbidity and mortality trends associated with elderly populations. Here, our group analyzes the complication rates and mortality data of elderly patients receiving care for facial fractures.