Since the emergence of SARS-CoV-2, several animal species have been studied to identify potential reservoirs and/or intermediate hosts of the virus. Scientists from the Institut Pasteur du Laos and the National University of Laos recently set out to shed light on the evolution of SARS-CoV-2 and explore the potential presence of SARS-CoV-2-related coronaviruses in the natural environment by carrying out a field mission in northern Laos on various bat species living in limestone caves. By analyzing samples collected during the mission, scientists from the Institut Pasteur, Université de Paris and the Alfort National Veterinary School (EnvA) were able to identify the existence of SARS-CoV-2-like viruses in the bats. These viruses recognize human cells with an efficacy similar to that of the original strain of the SARS-CoV-2 virus. The findings were published as a preprint on Research Square on September 17, 2021, prior to peer review with a view to future publication in a scientific journal.
Previous studies have suggested that SARS-CoV-2 is likely to have come from insectivorous bats, given its genomic proximity with various bat coronaviruses. But until now no coronaviruses in bats had presented a receptor-binding domain that effectively recognizes the receptor in human cells, like the receptor-binding domain identified in SARS-CoV-2. To identify the existence of SARS-CoV-2-related animal coronaviruses in the natural environment, a team of Lao scientists carried out a field mission on bats living in limestone habitats in northern Laos.
Scientists from the Institut Pasteur du Laos and the Faculty of Environmental Sciences at the National University of Laos took samples from the bats. Their colleagues from the Institut Pasteur, Université de Paris and the Alfort National Veterinary School (EnvA) then sequenced the genomes of the viruses discovered. They identified three viruses in particular (BANAL-103, BANAL-236 and BANAL-52) with genomic similarities to SARS-CoV-2, especially in a key domain of the spike protein that enables the virus to bind to host cells. Using direct affinity measurements, crystallography and computational simulations of molecular dynamics, the scientists demonstrated that the affinity of these three bat coronaviruses for the human ACE2 receptor is similar to that of the SARS-CoV-2 virus, and that they are also able to enter human cells via the same receptor. The reserchers then proved that the BANAL-236 virus was effectively able to muliply within human cells.
But the scientists showed that the viruses do not have a furin cleavage site, as is found in SARS-CoV-2. Furin is a protease that cleaves the spike protein, allowing the virus membrane to fuse with the human cell membrane. This cleavage site plays a key role in mediating viral entry into respiratory epithelial cells.
"The existence of these viruses discovered in the bat animal reservoir backs up the theory that SARS-CoV-2 may originate from bats living in the vast karst highlands in the Indochina peninsula, which stretches across Laos, Vietnam and China. Our results suggest that other related viruses could represent a risk for human health," explains Marc Eloit, Head of the Pathogen Discovery laboratory at the Institut Pasteur and a Professor of Virology at the Alfort National Veterinary School.
The identification of these new coronaviruses opens up new avenues for investigation into host-virus interactions and could improve our understanding of the factors that led to the emergence of the SARS-CoV-2 virus.
These findings were published as a preprint prior to peer review with a view to future publication in a scientific journal.
 Furin mediates cleavage of the spike protein in order to activate it, thereby enabling newly synthesized viruses in the organism to infect their target cells more easily.
Bat sarbecoviruses from Upper Mekong harbor receptor-binding domains close to SARS-CoV-2 that mediate entry in human cells through an ACE2 pathway, article prépublié sur Research Square, Septembre 17, 2021
Sarah Temmam* (1,2), Khamsing Vongphayloth* (3), Eduard Baquero Salazar* (4), Sandie Munier * (5,7), Massimiliano Bonomi* (8), Beatrice Regnault (1,2), Bounsavane Douangboubpha (9), Yasaman Karami (8), Delphine Chrétien (1,2), Daosavanh Sanamxay (9), Vilakhan Xayaphet (9), Phetphoumin Paphaphanh (9), Vincent Lacoste (3), Somphavanh Somlor (3), Khaithong Lakeomany (3), Nothasin Phommavanh (3), Philippe Pérot (1,2), Flora Donati (5,6), Thomas Bigot (1,10), Michael Nilges (8), Félix Rey (4), Sylvie van der Werf (5,6,7), Paul T. Brey (3), Marc Eloit + (1,2,11).
1) Institut Pasteur, Pathogen Discovery Laboratory, 25-28 rue du Dr. Roux, 75015, Paris, France.
2) Institut Pasteur, The OIE Collaborating Center for the detection and identification in humans of emerging animal pathogens, 25-28 rue du Dr. Roux, 75015, Paris, France
3) Institut Pasteur du Laos, Samsenthai Road, Ban Kao-Gnot, Sisattanak District, 3560 Vientiane, Lao PDR
4) Institut Pasteur, Structural Virology Unit, CNRS UMR3569, 25-28 rue du Dr. Roux, 75015, Paris, France.
5) Institut Pasteur, Unit of Molecular Genetics of RNA Viruses, UMR 3569 CNRS, Université de Paris, Paris, France.
6) Institut Pasteur, National Reference Center for Respiratory Viruses, 25-28 rue du Dr. Roux, 75015, Paris, France.
7) Université de Paris, Sorbonne Paris Cité, Paris, France.
8) Institut Pasteur, Structural Bioinformatics Unit, Department of Structural Biology and Chemistry; CNRS UMR 3528; C3BI, CNRS USR 3756; 25-28 rue du Dr. Roux, 75015, Paris, France
9) Faculty of Environmental Sciences, National University of Laos, Dong Dok Campus, P.O. Box: 7322, Xaythany District, Vientiane Capital, Lao PDR
10) Institut Pasteur, Bioinformatic and Biostatistic Hub - Computational Biology Department, 25-28 rue du Dr. Roux, 75015, Paris, France.
11) École Nationale Vétérinaire d’Alfort, 94704 Maisons-Alfort, France