OmniVira

Molecular basis of sarbecovirus evolution and receptor tropism in natural hosts, potential intermediate hosts, and humans.

Yusuke Kosugi1,2 Kanata Matsumoto3 Spyros Lytras1,4 Arnon Plianchaisuk5 Jarel Elgin Tolentino1,6 Shigeru Fujita1,2 Maximilian Stanley Yo1,6 Chen Luo1,4 Yoonjin Kim7 Wataru Shihoya3 Jumpei Ito1,8 Osamu Nureki3 Kei Sato1,9,10,11,12,13,14,15,16
Affiliations 16 institutions
  1. Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  2. Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  3. Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  4. MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
  5. Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  6. Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
  7. Department of Life Sciences, Faculty of Natural Science, Imperial College London, London, UK.
  8. International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  9. Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  10. MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
  11. Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan
  12. International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  13. International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  14. Collaboration Unit for Infection, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan
  15. Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  16. Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore. Electronic address: [email protected].
PMID40934083 DOI10.1016/j.celrep.2025.116220 Year2025 Journal Cell reports Cell Rep Languageeng Publication statusActive
Active Last checked 2026-09-30 03:30:39 Source: NCBI PubMed

Abstract

The spike protein of many sarbecoviruses binds to the angiotensin-converting enzyme 2 (ACE2) receptor and facilitates viral entry. The diversification of the sarbecovirus spike gene and the mammalian ACE2 gene suggests that sarbecoviruses and their hosts have co-evolved, and the genetic diversity in these genes affects the host tropism of sarbecoviruses. Better comprehending the evolutionary potential of sarbecoviruses can lead to preparedness for the next pandemic. However, the host tropism of sarbecoviruses is not fully understood. Here, we performed pseudovirus infection assays using 53 sarbecoviruses and ACE2s from 17 mammals to elucidate the ACE2 tropism of sarbecoviruses in natural hosts, potential intermediate hosts, and humans. We determined the factors responsible for the ACE2 tropism of sarbecoviruses through structural and phylogenetic analyses and infection experiments, revealing which substitutions can expand the host range of sarbecoviruses. These results highlight the mechanisms modulating host tropism throughout sarbecovirus evolution.

Supporting text Virus Host Location
ACE2 55 CP: Microbiology 7 evolution 65 sarbecovirus 20 SARS-CoV-2 556 spillover 109 Evolution, Molecular 178 Receptors, Virus 208 Viral Tropism 46 Angiotensin-Converting Enzyme 2 178 Animals 1981 Host Specificity 135 Humans 1455 Phylogeny 826 ACE2 protein, human 87

Evidence records

1 total
Genomic Evolution
1 records · 1 evidence types
Evidence type Phylogenetic Evolution
1 records
OVE9852 Phylogenetic Evolution
Key finding

Phylogenetic analysis showed co-evolution between sarbecovirus spike genes and mammalian ACE2 genes, with diversification patterns affecting viral host tropism.

Virus
Sarbecovirus
Host
mammals Mammalia Context pending
Location
Not specified
Supporting text

The diversification of the sarbecovirus spike gene and the mammalian ACE2 gene suggests that sarbecoviruses and their hosts have co-evolved, and the genetic diversity in these genes affects the host tropism of sarbecoviruses.

Genes or proteins
spike gene | ACE2 gene
Analysis methods
phylogenetic analysis | comparative genomic analysis