ArticlebioRxiv : the preprint server for biology2025
Structural and phenotypic plasticity of the RBD loop2 region is a key determinant for HKU5r-CoVs' emergence in mink.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
7 authors.
Funding
Abstract
The emergence of novel coronaviruses from animal reservoirs continues to pose a significant zoonotic threat. Here, we investigate the evolutionary origins and virological properties of a recently reported mink-derived HKU5-related coronavirus (nvHKU5r-CoV). Phylogenetic and recombination analyses reveal that nvHKU5r-CoV originated from bat HKU5-like viruses circulating in southeastern China. We characterize the spike loop2 region as a critical determinant of ACE2 receptor specificity, directly interacting with the receptor, and show that the bat HKU5r-CoV with the closest loop2 sequence to nvHKU5r-CoV could already utilize mink ACE2. Using AlphaFold3, we predicted spike-ACE2 binding interfaces consistent with our experimental infectivity results. Targeted mutagenesis demonstrates that a single amino acid substitution (R548S) enables robust entry of nvHKU5r-CoV via human ACE2. We further show that this substitution can arise
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