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RaTG13

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BatCoV RaTG13
Virus classification e
(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 that infects 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. As of 2020, it is the closest known relative of SARS-CoV-2, the virus that causes COVID-19.[4][5]

History

In spring 2012, three miners cleaning bat feces in an abandoned copper mine near the town of Tongguan in Mojiang Hani Autonomous County developed fatal pneumonia.[6] Out of concerns that the miner's cases could represent a novel disease,[7] 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][8][6]

In order to discover the possible cause of the infection, different animals (including bats, rats, and musk shrews) were sampled in and around the mining cave. Between 2012 and 2015, Shi Zhengli and her group isolated 293 diverse coronaviruses (284 alphacoronaviruses and 9 betacoronaviruses) from bat feces samples in the cave. One of the samples collected in 2013 from Rhinolophus affinis bat feces was the bat coronavirus RaTG13. The strain name was derived from the originating bat species, geographic location, and year collected.[3][8]

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 virus was renamed from the original Ra4991 to RatG13, to reflect the species of bat from which the virus was collected (Rhinolophus affinis), the location where it was collected (Tongguan) and the year of the sample’s collection (2013).[9] The change of name of the virus has been considered as innuendo by lab leak advocates.[9]

Virology

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 helper nonstructural proteins, including NS3, NS6, NS7a, NS7b and NS8, which are common in coronaviruses.[10]

RaTG13 bears strong resemblance to the SARS-CoV-2 virus (it shares 96.1% nucleotide similarity), and its existence is a supporting piece of evidence for SARS-CoV-2's natural origin.[11] The difference 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, indicating that the RaTG13 virus might not use angiotensin-converting enzyme 2 (ACE2) as its entry site into the cell as does SARS-CoV-2.[12] Further, the S protein of RaTG13 virus lacks the furin cleavage motif RRAR↓S.[12]

The binding affinity between RATG13 and hACE2 is lower than that between SARS-CoV-2 RBD and hACE2.[13]

Phylogenetics

Phylogenetic tree

A phylogenetic tree based on whole-genome sequences of SARS-CoV-2 and related coronaviruses is:[14][15]

SARS‑CoV‑2 related coronavirus
 

Rc-o319, 81% to SARS-CoV-2, Rhinolophus cornutus, Iwate, Japan[16]

 
 
 
 

SL-ZXC21, 88% to SARS-CoV-2, Rhinolophus pusillus, Zhoushan, Zhejiang[17]

 
 

SL-ZC45, 88% to SARS-CoV-2, Rhinolophus pusillus, Zhoushan, Zhejiang[17]

 
 
 
 

Pangolin SARSr-CoV-GX, 89% to SARS-CoV-2, Manis javanica, Smuggled from Southeast Asia[18]

 
 
 

Pangolin SARSr-CoV-GD, 91% to SARS-CoV-2, Manis javanica, Smuggled from Southeast Asia[19]

 
 
 
 

RshSTT182, 92.6% to SARS-CoV-2, Rhinolophus shameli, Steung Treng, Cambodia[20][unreliable source?]

 
 

RshSTT200, 92.6% to SARS-CoV-2, Rhinolophus shameli, Steung Treng, Cambodia[20][unreliable source?]

 
 
 
 

RacCS203, 91.5% to SARS-CoV-2, Rhinolophus acuminatus, Chachoengsao, Thailand[15]

 
 

RmYN02, 93.3% to SARS-CoV-2, Rhinolophus malayanus Mengla, Yunnan[21]

 
 
 

RpYN06, 94.4% to SARS-CoV-2, Rhinolophus pusillus, Xishuangbanna, Yunnan[14]

 
 
 

RaTG13, 96.1% to SARS-CoV-2, Rhinolophus affinis, Mojiang, Yunnan

 
 

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. ^ Jump up to: a b c d 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. PMID 33199918.
  4. ^ Poudel U, Subedi D, Pantha S, Dhakal S (October 2020). "Animal coronaviruses and coronavirus disease 2019: Lesson for One Health approach". Open Veterinary Journal. 10 (3): 239–251. doi:10.4314/ovj.v10i3.1. PMC 7703617. PMID 33282694.
  5. ^ Xiao C, Li X, Liu S, Sang Y, Gao SJ, Gao F (2020). "HIV-1 did not contribute to the 2019-nCoV genome". Emerging Microbes & Infections. 9 (1): 378–381. doi:10.1080/22221751.2020.1727299. PMC 7033698. PMID 32056509.
  6. ^ Jump up to: a b Wu Z, Yang L, Yang F, Ren X, Jiang J, Dong J, et al. (June 2014). "Novel Henipa-like virus, Mojiang Paramyxovirus, in rats, China, 2012". Emerging Infectious Diseases. 20 (6): 1064–6. doi:10.3201/eid2006.131022. PMC 4036791. PMID 24865545.
  7. ^ "The 'Occam's Razor Argument' Has Not Shifted in Favor of a Lab Leak". Snopes.com. Snopes. Retrieved 18 July 2021.
  8. ^ Jump up to: 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.
  9. ^ Jump up to: a b "The 'Occam's Razor Argument' Has Not Shifted in Favor of a COVID Lab Leak". Snopes.com. Snopes.
  10. ^ "Bat coronavirus RaTG13, complete genome". NCBI. Retrieved 2020-03-28.
  11. ^ Hakim MS (February 2021). "SARS-CoV-2, Covid-19, and the debunking of conspiracy theories". Reviews in Medical Virology (Review): e2222. doi:10.1002/rmv.2222. PMC 7995093. PMID 33586302.
  12. ^ Jump up to: 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.
  13. ^ 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.
  14. ^ Jump up to: a b Zhou H, Ji J, Chen X, Bi Y, Li J, Wang Q, et al. (June 2021). "Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses". Cell: S0092867421007091. doi:10.1016/j.cell.2021.06.008. PMC 8188299. PMID 34147139.
  15. ^ Jump up to: a b Wacharapluesadee S, Tan CW, Maneeorn P, Duengkae P, Zhu F, Joyjinda Y, et al. (February 2021). "Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia". Nature Communications. 12 (1): 972. doi:10.1038/s41467-021-21240-1. PMC 7873279. PMID 33563978.
  16. ^ 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.
  17. ^ Jump up to: 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.
  18. ^ 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. doi:10.1038/s41586-020-2169-0. PMID 32218527. S2CID 214683303.
  19. ^ Liu P, Jiang JZ, Wan XF, Hua Y, Li L, Zhou J, et al. (May 2020). "Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)?". PLOS Pathogens. 16 (5): e1008421. doi:10.1371/journal.ppat.1008421. PMC 7224457. PMID 32407364.
  20. ^ Jump up to: a b Hul V, Delaune D, Karlsson EA, Hassanin A, Tey PO, Baidaliuk A, et al. (26 January 2021). "A novel SARS-CoV-2 related coronavirus in bats from Cambodia". bioRxiv 10.1101/2021.01.26.428212.
  21. ^ 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.
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