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Updated: Jan 10, 2026

CRISPR-Mediated Reorganization of Chromatin Loop Structure
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CRISPR-Mediated Reorganization of Chromatin Loop Structure

Published on: September 14, 2018

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Structural and phenotypic plasticity of the RBD loop2 region is a key determinant for HKU5r-CoVs' emergence in mink

Jarel Elgin Tolentino1,2, Victoria A Jefferson3, Nicholas J Catanzaro4

  • 1Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Biorxiv : the Preprint Server for Biology
|November 24, 2025
PubMed

Insights

Novel bat coronaviruses (CoVs) can jump to humans, with mink farming identified as a key risk factor. A single mutation in the spike protein allows bat HKU5r-CoVs to infect human cells, highlighting zoonotic potential.

Area of Science:

  • Virology
  • Evolutionary Biology
  • Zoonotic Diseases

Background:

  • Novel coronaviruses emerging from animal reservoirs present a significant zoonotic threat.
  • Mink-derived HKU5-related coronavirus (nvHKU5r-CoV) has been recently identified.

Purpose of the Study:

  • To investigate the evolutionary origins and virological properties of nvHKU5r-CoV.
  • To identify the molecular determinants of ACE2 receptor specificity and zoonotic potential.

Main Methods:

  • Phylogenetic and recombination analyses were used to determine viral origins.
  • Spike protein loop2 region function was characterized through experimental assays and targeted mutagenesis.
  • AlphaFold3 was employed to predict spike-ACE2 binding interfaces.
  • Molecular dating was utilized to estimate transmission timelines.

Main Results:

  • nvHKU5r-CoV originated from bat HKU5-like viruses in China.
  • The spike loop2 region is a critical determinant of ACE2 receptor specificity.
  • A single amino acid substitution (R548S) in the spike protein enables efficient human ACE2 entry.
  • Bat HKU5r-CoVs can utilize mink ACE2, and transmission to mink occurred within the last decade.
  • Fur farming in China is associated with increased risk of bat coronavirus spillover.

Conclusions:

  • nvHKU5r-CoV possesses significant zoonotic potential, originating from bats and capable of infecting humans via a single mutation.
  • The study highlights fur farming as a critical risk factor for bat coronavirus spillover into farmed animals and potentially humans.
  • Understanding the molecular and structural basis of viral zoonosis is crucial for pandemic preparedness.

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