Integrated computational characterization of valosin-containing protein double-psi β-barrel domain: Insights into structural stability, binding mechanisms, and evolutionary significance.

Valosin-containing protein (VCP) plays a crucial role in various cellular processes, yet the molecular mechanisms and structural dynamics of its double-psi β-barrel (DPBB) domain, particularly in human, remain insufficiently explored. While previous studies have characterized the VCP_DPBB domain in other organisms, such as thermoplasma acidophilum and methanopyrus kandleri, its evolutionary conservation, binding potential, and stability in human require further investigation. To address this gap, we first employed all-atom molecular dynamics (AAMD) simulations to examine the structural dynamics of the human VCP_DPBB domain.

Bebtelovimab-bound SARS-CoV-2 RBD mutants: resistance profiling and validation with escape mutations, clinical results, and viral genome sequences.

The dynamic evolution of SARS-CoV-2 variants necessitates ongoing advancements in therapeutic strategies. Despite the promise of monoclonal antibody (mAb) therapies like bebtelovimab, concerns persist regarding resistance mutations, particularly single-to-multipoint mutations in the receptor-binding domain (RBD). Our study addresses this by employing interface-guided computational protein design to predict potential bebtelovimab-resistance mutations.

Interface design of SARS-CoV-2 symmetrical nsp7 dimer and machine learning-guided nsp7 sequence prediction reveals physicochemical properties and hotspots for nsp7 stability, adaptation, and therapeutic design.

The COVID-19 pandemic, driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates a profound understanding of the virus and its lifecycle. As an RNA virus with high mutation rates, SARS-CoV-2 exhibits genetic variability leading to the emergence of variants with potential implications. Among its key proteins, the RNA-dependent RNA polymerase (RdRp) is pivotal for viral replication.