Molecular In-Depth on the Epidemiological Expansion of SARS-CoV-2 XBB.1.5

Area of Science:

• Virology
• Genomics
• Immunoinformatics

Background:

• The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, such as XBB.1.5, is a recurring challenge during the pandemic.
• Understanding the potential hazard of novel subvariants is crucial for public health preparedness.

Purpose of the Study:

• To assess the potential risk and viral expansion capabilities of the SARS-CoV-2 XBB.1.5 subvariant.
• To provide a comprehensive viewpoint by integrating genetic, structural, and immunoinformatic analyses.

Main Methods:

• Genome-based integrative approach combining phylodynamics and structural/immunoinformatic analyses.
• Bayesian Skyline Plot (BSP) analysis to infer population dynamics and evolutionary rates.
• Detailed molecular analysis of key domains (NTD, RBD) and mutations.

Main Results:

• The viral population size and lineage count for XBB.1.5 peaked around November 24, 2022, with a relatively low evolutionary rate (6.9 × 10^-4 subs/sites/years).
• Key differences between XBB.1 and XBB.1.5 are located in the RBD, specifically at position 486.
• XBB.1.5 exhibits slower spread compared to other concerning 2022 subvariants and lacks features indicating a high risk of global expansion.

Conclusions:

• The multidisciplinary analysis of XBB.1.5 does not support evidence of a particularly high risk for viral expansion.
• Based on its current molecular characteristics, XBB.1.5 is unlikely to become a new global public health threat and is not the most dangerous variant.