Comprehensive analysis of liquid-liquid phase separation propensities of HSV-1 proteins and their interaction with host factors.

In recent years, it has been shown that the liquid-liquid phase separation (LLPS) of virus proteins plays a crucial role in their life cycle. It promotes the formation of viral replication organelles, concentrating viral components for efficient replication and facilitates the assembly of viral particles. LLPS has emerged as a crucial process in the replication and assembly of herpes simplex virus-1 (HSV-1). Recent studies have identified several HSV-1 proteins involved in LLPS, including the myristylated tegument protein UL11 and infected cell protein 4; however, a complete proteome-level understanding of the LLPS-prone HSV-1 proteins is not available. We provide a comprehensive analysis of the HSV-1 proteome and explore the potential of its proteins to undergo LLPS. By integrating sequence analysis, prediction algorithms and an array of tools and servers, we identified 10 HSV-1 proteins that exhibit high LLPS potential. By analysing the amino acid sequences of the LLPS-prone proteins, we identified specific sequence motifs and enriched amino acid residues commonly found in LLPS-prone regions. Our findings reveal a diverse range of LLPS-prone proteins within the HSV-1, which are involved in critical viral processes such as replication, transcriptional regulation and assembly of viral particles. This suggests that LLPS might play a crucial role in facilitating the formation of specialized viral replication compartments and the assembly of HSV-1 virion. The identification of LLPS-prone proteins in HSV-1 opens up new avenues for understanding the molecular mechanisms underlying viral pathogenesis. Our work provides valuable insights into the LLPS landscape of HSV-1, highlighting potential targets for further experimental validation and enhancing our understanding of viral replication and pathogenesis.

Amyloid Cross-Seeding: Mechanism, Implication, and Inhibition.

Most neurodegenerative diseases such as Alzheimer's disease, type 2 diabetes, Parkinson's disease, etc. are caused by inclusions and plaques containing misfolded protein aggregates. These protein aggregates are essentially formed by the interactions of either the same (homologous) or different (heterologous) sequences. Several experimental pieces of evidence have revealed the presence of cross-seeding in amyloid proteins, which results in a multicomponent assembly; however, the molecular and structural details remain less explored. Here, we discuss the amyloid proteins and the cross-seeding phenomena in detail. Data suggest that targeting the common epitope of the interacting amyloid proteins may be a better therapeutic option than targeting only one species. We also examine the dual inhibitors that target the amyloid proteins participating in the cross-seeding events. The future scopes and major challenges in understanding the mechanism and developing therapeutics are also considered. Detailed knowledge of the amyloid cross-seeding will stimulate further research in the practical aspects and better designing anti-amyloid therapeutics.