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Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor
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The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.
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“SARS-related coronaviruses appear frequently in bats (proximal source) [30].”
From Waves and variants of SARS-CoV-2: understanding the causes and effect of the COVID-19 catastrophe (2022) · cites this paper as [30]
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Metadata
- Authors
- Ge, X.-Y., Li, J.-L., Yang, X.-L., Chmura, A. A., Zhu, G., Epstein, J. H., Mazet, J. K., Hu, B., Zhang, W., Peng, C., Zhang, Y.-J., Luo, C.-M., Tan, B., Wang, N., Zhu, Y., Crameri, G., Zhang, S.-Y., Wang, L.-F., Daszak, P., & Shi, Z.-L.
- Affiliations
- Chinese Academy of Sciences (CN)
- EcoHealth Alliance (US)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Corresponding author
- Daszak, Peter
- Shi, Zheng-Li
- ORCID
- Venue
- Nature
- Published
- 2013-10-30
- Volume
- 503
- Issue
- 7477
- Pages
- 535-538
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5389864
- OpenAlex
- W1993577573
- Cited by
- 1,778
- References
- 30
- Citations by year
- 2026: 39 · 2025: 67 · 2024: 83 · 2023: 120 · 2022: 205 · 2021: 356 · 2020: 580 · 2019: 48 · 2018: 46 · 2017: 54 · 2016: 60 · 2015: 55 · 2014: 55 · 2013: 7
- FWCI
- 43.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons - University of South Florida (University of South Florida) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- U.S. Department of Health and Human Services
- United States Agency for International Development
- Commonwealth Scientific and Industrial Research Organisation
- National Natural Science Foundation of China (2013FY113500, 81290341, 2010CB530100, 31321001)
- Southern Medical University
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI110964, R01AI079231)
- Fogarty International Center (R01TW005869, R56TW009502)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Zoonotic diseases and public health
- Keywords
- SARS-like coronaviruses, bat coronaviruses, Chinese horseshoe bat, horseshoe bats, ACE2 receptor, bat-to-human transmission, spike protein receptor-binding domain, MERS-CoV, coronavirus phylogeny, Yunnan
- MeSH terms
- Angiotensin-Converting Enzyme 2, Animals, Chlorocebus aethiops, China, Chiroptera, Disease Reservoirs, Feces, Fluorescent Antibody Technique, Humans, Peptidyl-Dipeptidase A, Molecular Sequence Data, Receptors, Virus, Species Specificity, Vero Cells, Virion, Genome, Viral, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Viverridae, Virus Internalization, Host Specificity, Pandemics, Real-Time Polymerase Chain Reaction, Spike Glycoprotein, Coronavirus
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