A researcher at University of Tsukuba analyzed mutation patterns in the spike protein of the SARS-CoV-2 Delta variant. Two of the seven amino acid substitutions that emerged with the Delta variant resulted from cytosine-to-guanine (C-to-G) nucleotide substitutions, a mutation type that is among the rarest observed during SARS-CoV-2 evolution. A comparison with other major variants and within-lineage viral evolution revealed that the frequency was significantly higher than expected, indicating an unusual mutational pattern in the Delta spike protein. These findings offer new insight into the evolutionary processes associated with the emergence of highly transmissible SARS-CoV-2 variants.

Despite advances in computational biology and regulatory moves to reduce animal use, a coherent framework for AI-driven polypharmacology as a bridge between animal models and human drug development is still missing. The shift from "cage" to "code" brings opportunities but also unresolved issues in biological interpretation, regulation, and education. This review critically examines this transition within the 3R framework, focusing on: (i) regulatory and ethical drivers for non-animal methods, (ii) gaps left by reduced animal use, and (iii) AI's potential to reconstruct biological complexity via multi-omics and predictive modelling. The review suggests that AI-driven polypharmacology offers a scalable, ethical, and precision-oriented path forward.