Virological characteristics of SARS-CoV-2-related coronaviruses dynamically circulating in Southeast Asia.

Supaporn Wacharapluesadee1 Wilaiporn Saikruang2 Spyros Lytras3,4 Kanata Matsumoto5 Keiya Uriu2 Alfredo Hinay2 Ziyi Guo2 Khwankamon Rattanatumhi6 Ananporn Supataragul6 Sasiprapa Ninwattana6 Nattakarn Thippamom6 Tanawut Srisuk6 Patarapol Maneeorn7 Kirana Noradechanon7 Prateep Duengkae8 Nutthinee Sirichan8 Yusuke Kosugi3,9 Shigeru Fujita3,9 Maximilian Stanley Yo3,10 Ryo Matsunaga11,12 Bingjie Hu13 Lianzhao Du13 Lei Wang14,15 Masumi Tsuda14,15 Yoshitaka Oda16 Hesham Nasser17,18 Kanako Terakado Kimura19 Hiroaki Akasaka5 Hiroyuki Asakura20 Mami Nagashima20 Kenji Sadamasu20 Kazuhisa Yoshimura20 Yuki Yamamoto21 Tetsuharu Nagamoto21 Takanori Asakura22,23 Wataru Shihoya5 Takao Hashiguchi19 Terumasa Ikeda24 Shinya Tanaka14,25,26 Hin Chu13 Kouhei Tsumoto11,27,28 Osamu Nureki5 Genotype to Phenotype Japan (G2P-Japan) Consortium Genotype to Phenotype Asia (G2P-Asia) Consortium Arnon Plianchaisuk2 Opass Putcharoen29,30 Kei Sato3,31,32,33,34,35,36,37,38
Affiliations 38 institutions
  1. Thai Red Cross Emerging Infectious Diseases Clinical Center, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Electronic address: [email protected].
  2. Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  3. Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  4. MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
  5. Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  6. Thai Red Cross Emerging Infectious Diseases Clinical Center, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  7. Department of National Parks, Wildlife and Plant Conservation, Ministry of Natural Resources and Environment, Bangkok, Thailand.
  8. Department of Forest Biology, Faculty of Forestry, Kasetsart University, Bangkok, Thailand.
  9. Department of Pathology, Immunology and Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  10. Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
  11. Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan
  12. Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, Japan.
  13. State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  14. Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan
  15. Institute for Chemical Reaction Design and Discovery (ICReDD), Hokkaido University, Sapporo, Japan.
  16. Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
  17. Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan
  18. Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
  19. Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
  20. Tokyo Metropolitan Institute of Public Health, Tokyo, Japan.
  21. HiLung Inc., Kyoto, Japan.
  22. Laboratory of Bioregulatory Medicine, Department of Clinical Medicine, Kitasato University School of Pharmacy, Tokyo, Japan
  23. Department of Respiratory Medicine, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
  24. Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan.
  25. Institute for Chemical Reaction Design and Discovery (ICReDD), Hokkaido University, Sapporo, Japan
  26. Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.
  27. Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, Japan
  28. Medical Proteomics Laboratory, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  29. Thai Red Cross Emerging Infectious Diseases Clinical Center, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  30. Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Electronic address: [email protected].
  31. MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
  32. Department of Pathology, Immunology and Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  33. Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan
  34. International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  35. International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  36. Collaboration Unit for Infection, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan
  37. Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  38. Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore. Electronic address: [email protected].

Abstract

By sampling horseshoe bats-the reservoir hosts of SARS-CoV-2-related coronaviruses (SC2r-CoVs)-in Thailand, we present two clades of SC2r-CoVs co-circulating in the same bat population. Through a comprehensive set of experimental approaches, including cryo-electron microscopy (cryo-EM), pseudovirus and live virus assays, and hamster experiments, we characterize the virological properties of these new viruses. We show that one of the two clades discovered in this study is able to bind the human angiotensin converting enzyme 2 (ACE2) receptor; however, it exhibits reduced fusogenicity and replication in vitro and lower pathogenicity and transmissibility compared with SARS-CoV-2. Phylogeography and recombination analyses reveal a complex evolutionary history for these viruses characterized by extensive, recent geographic movement and recombination with co-circulating virus lineages. Our findings provide new insights into the diversity of SC2r-CoVs dynamically co-circulating in Southeast Asia as well as the virological characteristics of these viruses relative to SARS-CoV-2.

Supporting text Virus Host Location
bat coronavirus 8 pathogenicity 54 phylogeography 35 Rhinolophus bats 3 sarbecovirus 19 SARS-CoV-2 550 spillover 105 transmissibility 13 Betacoronavirus 78 Coronavirus Infections 171 Angiotensin-Converting Enzyme 2 177 Animals 1948 Asia, Southeastern 10 Chiroptera 371 COVID-19 425 Cricetinae 41 Cryoelectron Microscopy 37 Humans 1440 Peptidyl-Dipeptidase A 57 Phylogeny 805 Phylogeography 30 Recombination, Genetic 59 SARS-CoV-2 453 Spike Glycoprotein, Coronavirus 274

Evidence records

6 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type
1 records
OVE11812
Key finding

Two clades of SARS-CoV-2-related coronaviruses were detected co-circulating in a horseshoe bat population in Thailand.

Virus
Host
Location
Supporting text

By sampling horseshoe bats... in Thailand, we present two clades of SC2r-CoVs co-circulating in the same bat population.

Method
sampling
Geographic raw
Thailand
Country inferred
THA
Experimental Infection
2 records · 2 evidence types
Evidence type
1 records
OVE11815
Key finding

In hamster experiments, one newly identified SC2r-CoV clade showed lower pathogenicity than SARS-CoV-2.

Virus
Host
Location
Not specified
Supporting text

hamster experiments ... we show that one of the two clades ... exhibits ... lower pathogenicity and transmissibility compared with SARS-CoV-2.

Method
hamster experiments
Experimental system
hamster experiments
Evidence type
1 records
OVE11814
Key finding

One clade of newly identified SARS-CoV-2-related coronaviruses from Thai horseshoe bats can use human ACE2 but shows reduced fusogenicity and replication in vitro compared with SARS-CoV-2.

Virus
Host
Experimental system
Location
Not specified
Supporting text

We show that one of the two clades discovered in this study is able to bind the human angiotensin converting enzyme 2 (ACE2) receptor; however, it exhibits reduced fusogenicity and replication in vitro...

Method
pseudovirus assay | live virus assay
Experimental system
pseudovirus and live virus in vitro assays assessing ACE2-mediated entry, fusion, and replication
Functional Mechanism
1 records · 1 evidence types
Evidence type
1 records
OVE11813
Key finding

One of the two SC2r-CoV clades identified in Thai horseshoe bats can bind the human ACE2 receptor.

Virus
Host
Location
Not specified
Supporting text

We show that one of the two clades discovered in this study is able to bind the human angiotensin converting enzyme 2 (ACE2) receptor

Method
cryo-electron microscopy (cryo-EM) | pseudovirus assays | live virus assays
Receptors
human angiotensin converting enzyme 2 (ACE2)
Genomic Evolution
2 records · 2 evidence types
Evidence type
1 records
OVE11817
Key finding

SARS-CoV-2-related coronaviruses from Thailand show recombination with co-circulating virus lineages.

Virus
Host
Not specified
Location
Not specified
Supporting text

Phylogeography and recombination analyses reveal a complex evolutionary history for these viruses characterized by ... recombination with co-circulating virus lineages.

Event type
recombination
Evidence type
1 records
OVE11816
Key finding

Phylogeographic analysis indicates SARS-CoV-2-related coronaviruses in Southeast Asia have a complex evolutionary history with extensive, recent geographic movement.

Virus
Host
Not specified
Location
Not specified
Supporting text

Phylogeography and recombination analyses reveal a complex evolutionary history for these viruses characterized by extensive, recent geographic movement

Analysis methods
Phylogeography