Bat coronaviruses related to SARS-CoV-2 and infectious for human cells

Sarah Temmam, Khamsing Vongphayloth, Eduard Baquero, Sandie Munier, Massimiliano Bonomi, Béatrice Regnault, Bounsavane Douangboubpha, Yasaman Karami, Delphine Chrétien, Daosavanh Sanamxay, Vilakhan Xayaphet, Phetphoumin Paphaphanh, Vincent Lacoste, Somphavanh Somlor, Khaithong Lakeomany, Nothasin Phommavanh, Philippe Pérot, Océane Dehan, Faustine Amara, Flora Donati, Thomas Bigot, Michael Nilges, Félix A. Rey, Sylvie van der Werf, Paul T. Brey and Marc Eloit ()
Additional contact information
Sarah Temmam: Université de Paris, Pathogen Discovery Laboratory
Khamsing Vongphayloth: Institut Pasteur du Laos
Eduard Baquero: Université de Paris, CNRS UMR 3569, Structural Virology Unit
Sandie Munier: Université de Paris, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit
Massimiliano Bonomi: Université de Paris, CNRS UMR 3528, Structural Bioinformatics Unit
Béatrice Regnault: Université de Paris, Pathogen Discovery Laboratory
Bounsavane Douangboubpha: National University of Laos
Yasaman Karami: Université de Paris, CNRS UMR 3528, Structural Bioinformatics Unit
Delphine Chrétien: Université de Paris, Pathogen Discovery Laboratory
Daosavanh Sanamxay: National University of Laos
Vilakhan Xayaphet: National University of Laos
Phetphoumin Paphaphanh: National University of Laos
Vincent Lacoste: Institut Pasteur du Laos
Somphavanh Somlor: Institut Pasteur du Laos
Khaithong Lakeomany: Institut Pasteur du Laos
Nothasin Phommavanh: Institut Pasteur du Laos
Philippe Pérot: Université de Paris, Pathogen Discovery Laboratory
Océane Dehan: Université de Paris, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit
Faustine Amara: Université de Paris, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit
Flora Donati: Université de Paris, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit
Thomas Bigot: Université de Paris, Pathogen Discovery Laboratory
Michael Nilges: Université de Paris, CNRS UMR 3528, Structural Bioinformatics Unit
Félix A. Rey: Université de Paris, CNRS UMR 3569, Structural Virology Unit
Sylvie van der Werf: Université de Paris, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit
Paul T. Brey: Institut Pasteur du Laos
Marc Eloit: Université de Paris, Pathogen Discovery Laboratory

Nature, 2022, vol. 604, issue 7905, 330-336

Abstract: Abstract The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV-2-related viruses in Asian Rhinolophus bats1–4, including the closest virus from R. affinis, RaTG13 (refs. 5,6), and pangolins7–9. SARS-CoV-2 has a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host range10–12. SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 (hACE2) pathway have not yet been identified, although they would be key in understanding the origin of the epidemic. Here we show that such viruses circulate in cave bats living in the limestone karstic terrain in northern Laos, in the Indochinese peninsula. We found that the receptor-binding domains of these viruses differ from that of SARS-CoV-2 by only one or two residues at the interface with ACE2, bind more efficiently to the hACE2 protein than that of the SARS-CoV-2 strain isolated in Wuhan from early human cases, and mediate hACE2-dependent entry and replication in human cells, which is inhibited by antibodies that neutralize SARS-CoV-2. None of these bat viruses contains a furin cleavage site in the spike protein. Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses that are potentially infectious for humans circulate in Rhinolophus spp. in the Indochinese peninsula.

Date: 2022
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DOI: 10.1038/s41586-022-04532-4

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