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RaTG13

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BatCoV RaTG13
Virus classification Edit this classification
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Pisuviricota
Class: Pisoniviricetes
Order: Nidovirales
Family: Coronaviridae
Genus: Betacoronavirus
Subgenus: Sarbecovirus
Species:
Severe acute respiratory syndrome–related coronavirus
Strain:
BatCoV RaTG13
Synonyms[1]
  • Bat coronavirus Ra4991

Bat coronavirus RaTG13 is a SARS-like betacoronavirus identified in the droppings of the horseshoe bat Rhinolophus affinis.[2][3] It was discovered in 2013 in bat droppings from a mining cave near the town of Tongguan in Mojiang county in Yunnan, China.[4] In February 2020,[5] it was identified as the closest known relative of SARS-CoV-2, the virus that causes COVID-19, sharing 96.1% nucleotide identity.[6][7] However, in 2022, scientists found three closer matches in bats found 530 km south, in Feuang, Laos, designated as BANAL-52 (96.8% identity), BANAL-103 and BANAL-236.[8][9][10]

History

In the spring of 2012, three miners cleaning bat feces in an abandoned copper mine near the town of Tongguan in Mojiang Hani Autonomous County developed fatal pneumonia.[11] Out of concerns that the miner's cases could represent a novel disease,[12] serum samples collected from the miners were sent to the Wuhan Institute of Virology and tested by Shi Zhengli and her group for Ebola virus, Nipah virus, and bat SARSr-CoV Rp3. The samples tested negative.[3][13][11]

To uncover a possible cause of the infection, different animals (including bats, rats, and musk shrews) were also sampled in and around the mining cave. Between 2012 and 2015, Shi Zhengli and her group isolated 293 different coronaviruses (284 alpha- and 9 beta-coronaviruses) from bat feces samples in the cave. One of the samples collected in 2013 from Rhinolophus affinis (the intermediate horseshoe bat) contained a novel sequence of ribonucleic acids later identified as "RaTG13".[3][13]

In 2020, Shi and her group retested the serum samples from the miners for SARS-CoV-2. The samples tested negative.[3]

In 2020, the strain identified in the sample was renamed from the original Ra4991 (4991st sample collected from Rhinolophus affinis) to "RaTG13", to reflect the originating bat species (Ra from Rhinolophus affinis), geographic location (TG from Tongguan), and year collected (13 from 2013).[14] The name change has been considered innuendo by advocates of the lab leak theory for the COVID-19 pandemic.[14]

Virology

The sequence of RaTG13 was reconstructed from metagenomic sampling (a common practice in environmental virology),[15] and as such, could potentially be an in-silico chimera.[16] RaTG13 has not been confirmed to exist in nature, to have been cultured or isolated in any laboratory,[12] or to be a viable human pathogen.[16] A live virus "RaTG13" has never been detected in any laboratory sample from the WIV or elsewhere.[16]

Based on its sequence, RaTG13 is a positive-strand RNA virus with an outer membrane. Its genome is approximately 29,800 nucleotides. The genome encodes a replicase (ORF1a/1b) and four structural proteins; including a spike protein (S), membrane protein (M), envelope protein (E) and nucleocapsid protein (N); and five viral accessory proteins, including ORF3a (NS3), ORF6 (NS6), ORF7a (NS7a), ORF7b (NS7b) and ORF8 (NS8).[3][17]

RaTG13 bears strong resemblance to the SARS-CoV-2 genome (it shares 96.1% nucleotide similarity), and its identification in animal droppings is a supporting piece of evidence for SARS-CoV-2's natural origin.[7] The main area of divergence between RaTG13 and SARS-CoV-2 is in the receptor-binding domain (RBD) of the spike protein (S), which is the portion that binds to the receptor protein on the surface of the host cell and causes infection. The divergence in this domain indicates that, unlike SARS-CoV-2, the RaTG13 virus might not use angiotensin-converting enzyme 2 (ACE2) as its entry site into the cell.[18] Further, the S protein of RaTG13 virus lacks the furin cleavage motif RRAR↓S.[18]

The binding affinity between RATG13 and hACE2 is lower than that between SARS-CoV-2 RBD and hACE2.[19]

Phylogenetics

Phylogenetic tree

A phylogenetic tree based on whole-genome sequences of SARS-CoV-2 and related coronaviruses is:[20][21]

SARS‑CoV‑2 related coronavirus

(Bat) Rc-o319, 81% to SARS-CoV-2, Rhinolophus cornutus, Iwate, Japan[22]

Bat SL-ZXC21, 88% to SARS-CoV-2, Rhinolophus pusillus, Zhoushan, Zhejiang[23]

Bat SL-ZC45, 88% to SARS-CoV-2, Rhinolophus pusillus, Zhoushan, Zhejiang[23]

Pangolin SARSr-CoV-GX, 85.3% to SARS-CoV-2, Manis javanica, smuggled from Southeast Asia[24]

Pangolin SARSr-CoV-GD, 90.1% to SARS-CoV-2, Manis javanica, smuggled from Southeast Asia[25]

Bat RshSTT182, 92.6% to SARS-CoV-2, Rhinolophus shameli, Steung Treng, Cambodia[26]

Bat RshSTT200, 92.6% to SARS-CoV-2, Rhinolophus shameli, Steung Treng, Cambodia[26]

(Bat) RacCS203, 91.5% to SARS-CoV-2, Rhinolophus acuminatus, Chachoengsao, Thailand[21]

(Bat) RmYN02, 93.3% to SARS-CoV-2, Rhinolophus malayanus, Mengla, Yunnan[27]

(Bat) RpYN06, 94.4% to SARS-CoV-2, Rhinolophus pusillus, Xishuangbanna, Yunnan[20]

(Bat) RaTG13, 96.1% to SARS-CoV-2, Rhinolophus affinis, Mojiang, Yunnan[28]

(Bat) BANAL-52, 96.8% to SARS-CoV-2, Rhinolophus malayanus, Vientiane, Laos[29]

SARS-CoV-2

SARS-CoV-1, 79% to SARS-CoV-2

See also

References

  1. ^ "Taxonomy browser (Bat coronavirus RaTG13)". www.ncbi.nlm.nih.gov. Retrieved 2021-01-02.
  2. ^ Ge XY, Wang N, Zhang W, Hu B, Li B, Zhang YZ, et al. (February 2016). "Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft". Virologica Sinica. 31 (1): 31–40. doi:10.1007/s12250-016-3713-9. PMC 7090819. PMID 26920708.
  3. ^ a b c d e Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. (December 2020). "Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 588 (7836): E6. Bibcode:2020Natur.588E...6Z. doi:10.1038/s41586-020-2951-z. PMC 9744119. PMID 33199918.
  4. ^ Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. (December 2020). "Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 588 (7836): E6. Bibcode:2020Natur.588E...6Z. doi:10.1038/s41586-020-2951-z. PMC 9744119. PMID 33199918.
  5. ^ Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. (March 2020). "A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 579 (7798): 270–273. Bibcode:2020Natur.579..270Z. doi:10.1038/s41586-020-2012-7. PMC 7095418. PMID 32015507.
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  8. ^ Temmam S, Vongphayloth K, Baquero E, Munier S, Bonomi M, Regnault B, et al. (April 2022). "Bat coronaviruses related to SARS-CoV-2 and infectious for human cells". Nature. 604 (7905): 330–336. Bibcode:2022Natur.604..330T. doi:10.1038/s41586-022-04532-4. PMID 35172323. S2CID 246902858.
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  13. ^ a b Ge XY, Wang N, Zhang W, Hu B, Li B, Zhang YZ, et al. (February 2016). "Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft". Virologica Sinica. 31 (1): 31–40. doi:10.1007/s12250-016-3713-9. PMC 7090819. PMID 26920708.
  14. ^ a b "The 'Occam's Razor Argument' Has Not Shifted in Favor of a COVID Lab Leak". Snopes.com. Snopes. 16 July 2021.
  15. ^ Harvey E, Holmes EC (June 2022). "Diversity and evolution of the animal virome". Nature Reviews. Microbiology. 20 (6): 321–334. doi:10.1038/s41579-021-00665-x. PMID 34983966. S2CID 245703661.
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  17. ^ "Bat coronavirus RaTG13, complete genome". NCBI. Retrieved 2020-03-28.
  18. ^ a b Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF (April 2020). "The proximal origin of SARS-CoV-2". Nature Medicine. 26 (4): 450–452. doi:10.1038/s41591-020-0820-9. PMC 7095063. PMID 32284615.
  19. ^ Liu K, Pan X, Li L, Yu F, Zheng A, Du P, et al. (June 2021). "Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species". Cell. 184 (13): 3438–3451.e10. doi:10.1016/j.cell.2021.05.031. PMC 8142884. PMID 34139177.
  20. ^ a b Zhou H, Ji J, Chen X, Bi Y, Li J, Wang Q, et al. (August 2021). "Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses". Cell. 184 (17): 4380–4391.e14. doi:10.1016/j.cell.2021.06.008. PMC 8188299. PMID 34147139.
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  22. ^ Murakami S, Kitamura T, Suzuki J, Sato R, Aoi T, Fujii M, et al. (December 2020). "Detection and Characterization of Bat Sarbecovirus Phylogenetically Related to SARS-CoV-2, Japan". Emerging Infectious Diseases. 26 (12): 3025–3029. doi:10.3201/eid2612.203386. PMC 7706965. PMID 33219796.
  23. ^ a b Zhou H, Chen X, Hu T, Li J, Song H, Liu Y, et al. (June 2020). "A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein". Current Biology. 30 (11): 2196–2203.e3. doi:10.1016/j.cub.2020.05.023. PMC 7211627. PMID 32416074.
  24. ^ Lam TT, Jia N, Zhang YW, Shum MH, Jiang JF, Zhu HC, et al. (July 2020). "Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins". Nature. 583 (7815): 282–285. Bibcode:2020Natur.583..282L. doi:10.1038/s41586-020-2169-0. PMID 32218527. S2CID 214683303.
  25. ^ Xiao K, Zhai J, Feng Y, Zhou N, Zhang X, Zou JJ, et al. (July 2020). "Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins". Nature. 583 (7815): 286–289. Bibcode:2020Natur.583..286X. doi:10.1038/s41586-020-2313-x. PMID 32380510. S2CID 256822274.
  26. ^ a b Delaune D, Hul V, Karlsson EA, Hassanin A, Ou TP, Baidaliuk A, et al. (November 2021). "A novel SARS-CoV-2 related coronavirus in bats from Cambodia". Nature Communications. 12 (1): 6563. Bibcode:2021NatCo..12.6563D. doi:10.1038/s41467-021-26809-4. PMC 8578604. PMID 34753934.
  27. ^ Zhou H, Chen X, Hu T, Li J, Song H, Liu Y, et al. (June 2020). "A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein". Current Biology. 30 (11): 2196–2203.e3. doi:10.1016/j.cub.2020.05.023. PMC 7211627. PMID 32416074.
  28. ^ Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. (March 2020). "A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 579 (7798): 270–273. Bibcode:2020Natur.579..270Z. doi:10.1038/s41586-020-2012-7. PMC 7095418. PMID 32015507.
  29. ^ Temmam S, Vongphayloth K, Baquero E, Munier S, Bonomi M, Regnault B, et al. (April 2022). "Bat coronaviruses related to SARS-CoV-2 and infectious for human cells". Nature. 604 (7905): 330–336. Bibcode:2022Natur.604..330T. doi:10.1038/s41586-022-04532-4. PMID 35172323. S2CID 246902858.
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