OmniVira

Literature detail

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

Sarah Temmam1,2 Khamsing Vongphayloth3 Eduard Baquero4 Sandie Munier5 Massimiliano Bonomi6 Béatrice Regnault1,2 Bounsavane Douangboubpha7 Yasaman Karami6 Delphine Chrétien1,2 Daosavanh Sanamxay7 Vilakhan Xayaphet7 Phetphoumin Paphaphanh7 Vincent Lacoste3 Somphavanh Somlor3 Khaithong Lakeomany3 Nothasin Phommavanh3 Philippe Pérot1,2 Océane Dehan5,8 Faustine Amara5 Flora Donati5,8 Thomas Bigot1,9 Michael Nilges6 Félix A Rey4 Sylvie van der Werf5,8 Paul T Brey3 Marc Eloit10,11,12
Affiliations 12 institutions
  1. Institut Pasteur, Université de Paris, Pathogen Discovery Laboratory, Paris, France.
  2. Institut Pasteur, Université de Paris, The OIE Collaborating Center for the Detection and Identification in Humans of Emerging Animal Pathogens, Paris, France.
  3. Institut Pasteur du Laos, Vientiane, Lao People's Democratic Republic.
  4. Institut Pasteur, Université de Paris, CNRS UMR 3569, Structural Virology Unit, Paris, France.
  5. Institut Pasteur, Université de Paris, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit, Paris, France.
  6. Institut Pasteur, Université de Paris, CNRS UMR 3528, Structural Bioinformatics Unit, Paris, France.
  7. Faculty of Environmental Sciences, National University of Laos, Vientiane, Lao People's Democratic Republic.
  8. Institut Pasteur, Université de Paris, National Reference Center for Respiratory Viruses, Paris, France.
  9. Institut Pasteur, Université de Paris, Bioinformatic and Biostatistic Hub - Computational Biology Department, Paris, France.
  10. Institut Pasteur, Université de Paris, Pathogen Discovery Laboratory, Paris, France. [email protected].
  11. Institut Pasteur, Université de Paris, The OIE Collaborating Center for the Detection and Identification in Humans of Emerging Animal Pathogens, Paris, France. [email protected].
  12. Ecole Nationale Vétérinaire d'Alfort, University of Paris-Est, Maisons-Alfort, France. [email protected].
PMID 35172323 2022 Nature eng ppublish
PubMed DOI Browse context

Article

Publication summary

The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV-2-related viruses in Asian Rhinolophus bats<sup>1-4</sup>, including the closest virus from R. affinis, RaTG13 (refs. <sup>5,6</sup>), and pangolins<sup>7-9</sup>. 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 range<sup>10-12</sup>. 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.

Chiroptera COVID-19 Angiotensin-Converting Enzyme 2 Animals Asia Caves Disease Reservoirs Humans Protein Binding SARS-CoV-2 Spike Glycoprotein, Coronavirus spike protein, SARS-CoV-2

Structured evidence records

Evidence records

3 total
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Bat SARS-CoV-2-like viruses with spike receptor-binding domain substitutions enhance binding to human ACE2 and support hACE2-dependent entry and replication, indicating molecular adaptation for potential human infection.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

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.

Genes or proteins
spike protein; receptor-binding domain
Receptors
ACE2; human ACE2 (hACE2)
Mechanism types
receptor_binding; cell_entry; replication_efficiency; host_range
Receptor Usage 1 records
Receptor Usage Extraction confidence 1.00
Key finding

Bat SARS-CoV-2-related coronaviruses from Rhinolophus bats in Laos show enhanced binding to human ACE2 and mediate hACE2-dependent entry and replication in human cells.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

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.

Method
binding assay; cell-entry assay
Receptors
ACE2
Zoonotic Surveillance 1 records
Zoonotic Surveillance Extraction confidence 0.90
Key finding

SARS-CoV-2-related coronaviruses were detected circulating in Rhinolophus bats in northern Laos, indicating active viral surveillance of bat populations.

Virus
SARS-CoV-2
Location
Laos northern Laos, Laos
Supporting text

Here we show that such viruses circulate in cave bats living in the limestone karstic terrain in northern Laos, in the Indochinese peninsula.

Geographic raw
northern Laos
Country inferred
Laos