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Discovery of a novel SARS-related coronavirus in bats

 


Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the 2019 coronavirus disease (COVID-19) pandemic, is a relatively recently identified coronavirus that has since spread worldwide. doing.

SARS-CoV-2 is considered a zoonotic disease in that at some point in late 2019 the virus is likely to have spilled from animals to human hosts.The exact origin of this virus is unknown, but it comes from a horseshoe-shaped bat or pangolin. Coronavirus.. Both of these zoonotic strains of coronavirus have many similarities to SARS-CoV-2 in that they differ. Therefore, ratifying which of these first caused SARS-CoV-2 remains a challenge.

In a recent study (Not peer-reviewed*). Published to bioRxiv* Server, Peng Zhou, Zheng-Li Shi, and colleagues at the Wuhan Institute of Virology have identified a new strain of SARS-related coronavirus that utilizes bat angiotensin converting enzyme with the help of scientists from the Chinese Academy of Sciences in China. did. 2 (ACE2) Cell invasion receptor. This is the same receptor that SARS-CoV-2 uses to infect host cells.

Study: Identification of a new strain of bat SARS-related coronavirus that uses the bat ACE2 receptor. Image Credit: Binturong-tonoscarpe / Shutterstock

RaTG13, RatG15, and other SARS-related coronaviruses

ACE2 is an enzyme present mainly in the cell membranes of respiratory, heart and liver cells in animals and is responsible for controlling blood pressure. SARS-CoV-2 uses ACE2 as a site of entry into host cells. SARS-CoV-2, followed by COVID-19, often causes respiratory symptoms after infection, as ACE2 is found primarily in the lungs and respiratory system.

Guo et al. Sampled bats captured in Yunnan in 2015 and used an anal swab to extract and store viral ribonucleic acid (RNA) for sequencing. Of the viruses found to be present in these bats, the team identified a virus strain, RaTG13, that is very similar to SARS-CoV-2, which shares 96.2% of genomic identity.

Discovery of a new strain of bat SARSr-CoV.  (A) Similarity plot analysis based on the full-length genome sequence of the bat SARSr-CoVRaTG15.  The complete 409-length genomic sequence of Pangolin CoV associated with SARS-CoV-1, SARS-CoV-2, bats and SARS-CoV-2 was used as the reference sequence. The analysis was performed on the Kimura model, window size 1500 base pairs, and step size 150 base pairs.  (B) A phylogenetic tree based on the complete genomic sequence of beta coronavirus. The tree was built by the neighbor-joining method using the Jukes-Cantor model with bootstrap values ​​determined by 1000 replications. Bootstrap /> 50% is displayed. The scale bar represents a 0.1 substitution per nucleotide position. The new SARSr-CoV characterized in this study is shown in bold.  Ra, Rhinolophus affinis; Rst, Rhinolophus stheno; Rsh, Rhinolophus shameli; Rs, Rhinolophus sinicus; Rac, Rhinolophus acuminatus; Rm, Rhinolophus malayanus; Rc, Murine coronavirus.” height =”2250″ src =”https://d2jx2rerrg6sh3.cloudfront.net/image-handler/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg” srcset =”https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/5421/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 5421w, https://d2jx2rerrg6sh3.cloudfront.net/image -handler / ts / 20210524115842 / ri / 5350 / picture / 2021/5 / Pages_from_2021.05.21.445091v1.full.jpg 5350w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/5150/ picture / 2021/5 / Pages_from_2021.05.21.445091v1.full.jpg 5150w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/4950/picture/2021/5/Pages_from_2021.05.21.445091v1 .full.jpg 4950w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/4750/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 4750w, https://d2jx2rerrg6sh3 .cloudfront.net/image-handler/ts/20210524115842/ri/4550/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 4550w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/ 20210524115842 / ri / 4350 / picture / 2021/5 / Pages_from_2021.05.21.445091v1.full.jpg 4350w, https://d2jx2rerrg6s  h3.cloudfront.net/image-handler/ts/20210524115842/ri/4150/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 4150w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts /20210524115842/ri/3950/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 3950w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/3750/picture/2021/ 5 / Pages_from_2021.05.21.445091v1.full.jpg 3750w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/3550/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 3550w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/3350/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 3350w, https://d2jx2rerrg6sh3.cloudfront.net /image-handler/ts/20210524115842/ri/3150/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 3150w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/ 2950 / picture / 2021/5 / Pages_from_2021.05.21.445091v1.full.jpg 2950w, https://d2jx2rerrg6sh3.cloudfront.net/im  age-handler / ts / 20210524115842/ri/2750/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 2750w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/2550 /picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 2550w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/2350/picture/2021/5/Pages_from_2021.05.21. 445091v1.full.jpg 2350w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/2150/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 2150w, https: // d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/1950/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 1950w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts /20210524115842/ri/1750/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 1750w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/1550/picture/2021/ 5 / Pages_from_2021.05.21.445091v1.full.jpg 1550w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210  524115842 / ri / 1350 / picture / 2021/5 / Pages_from_2021.05.21.445091v1.full.jpg 1350w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/1150/picture/2021/5 /Pages_from_2021.05.21.445091v1.full.jpg 1150w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/950/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 950w , https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/750/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 750w, https://d2jx2rerrg6sh3.cloudfront.net/ image-handler / ts / 20210524115842/ri/550/picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 550w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210524115842/ri/450 /picture/2021/5/Pages_from_2021.05.21.445091v1.full.jpg 450w” sizes =”(min-width: 1200px) 673px, (min-width: 1090px) 667px, (min-width: 992px) calc (66.6vw -60px), (min-width: 480px) calc (100vw -40px), calc (100vw) –30px)” title =”Discovery of a new strain of bat SARSr-CoV.  (A) Similarity plot analysis based on the full-length genome sequence of the bat SARSr-CoVRaTG15.  The complete 409-length genomic sequence of Pangolin CoV associated with SARS-CoV-1, SARS-CoV-2, bats and SARS-CoV-2 was used as the reference sequence. The analysis was performed on the Kimura model, window size 1500 base pairs, and step size 150 base pairs.  (B) A phylogenetic tree based on the complete genomic sequence of beta coronavirus. The tree was built by a neighbor-joining method using the Jukes-Cantor model with bootstrap values ​​determined by 1000 replications.  You will see over 50% bootstrap. The scale bar represents a 0.1 substitution per nucleotide position. The new SARSr-CoV characterized in this study is shown in bold.  Ra, Rhinolophus affinis; Rst, Rhinolophus stheno; Rsh, Rhinolophus shameli; Rs, Rhinolophus sinicus; Rac, Rhinolophus acuminatus; Rm, Rhinolophus malayanus; Rc, Murine coronavirus.” width =”5421″/></p>
<p><span style=Discovery of a new strain of bat SARSr-CoV. (A) Similarity plot analysis based on the full-length genome sequence of the bat SARSr-CoVRaTG15. The complete 409-length genomic sequence of Pangolin CoV associated with SARS-CoV-1, SARS-CoV-2, bats and SARS-CoV-2 was used as the reference sequence. The analysis was performed on the Kimura model, window size 1500 base pairs, and step size 150 base pairs. (B) A phylogenetic tree based on the complete genomic sequence of beta coronavirus. The tree was built by the neighbor-joining method using the Jukes-Cantor model with bootstrap values ​​determined by 1000 replications. You will see over 50% bootstrap. The scale bar represents a 0.1 substitution per nucleotide position. The new SARSr-CoV characterized in this study is shown in bold. Ra, Rhinolophus affinis; Rst, Rhinolophus stheno; Rsh, Rhinolophus shameli; Rs, Rhinolophus sinicus; Rac, Rhinolophus acuminatus; Rm, Rhinolophus malayanus; Rc, Murine coronavirus.

In addition, eight SARS-related coronaviruses were found to share 93.5% of genomic identity with SARS-CoV-2. These eight viruses were all nearly identical because they shared more than 99.7% of their genomic identity with each other.

One of these strains, RaTG15, is 95.3% similar to SARS-CoV-2 and 92.5% similar to SARS-CoV-1, the causative agent of SARS outbreaks from 2002 to 2003. I understand. Spike protein The sequences of RaTG15 and other strains showed deviations from other SARS-related coronaviruses and lacked the deletion present in SARS-CoV-2, which determines the use of ACE2.

Through further testing, the research team concluded that RaTG15 and its related strains could not have a potential zoonotic disease of SARS-CoV-2. This is in contrast to the pangoline coronavirus, which has a very high spillover effect on the use of cell receptors.

Conclusion

This new strain of SARS-related bat coronavirus sheds light on the potential origin of SARS-CoV-2. The RaTG13 and other SARS-related coronaviruses described in this article show minimal binding affinity for human ACE2, indicating that these viruses are unlikely to cause SARS-CoV-2. The likelihood of cross-species infection is significantly higher with the pangoline-related coronavirus, despite a high association (~ 99%) between SARS-CoV-2 and this new bat-CoV strain.

Researchers in this study emphasize that a more longitudinal sampling of bats and pangolins, as well as other intermediate animal hosts, is needed to fully understand the origin of the COVID-19 pandemic.

Important Notices

bioRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.

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