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Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity

View ORCID ProfileYong Jia, View ORCID ProfileGangxu Shen, View ORCID ProfileStephanie Nguyen, Yujuan Zhang, Keng-Shiang Huang, Hsing-Ying Ho, Wei-Shio Hor, Chih-Hui Yang, View ORCID ProfileJohn B Bruning, View ORCID ProfileChengdao Li, Wei-Lung Wang
doi: https://doi.org/10.1101/2020.04.09.034942
Yong Jia
1College of Science, Health, Engineering and Education, Murdoch University, Murdoch, WA, 6150, Australia
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  • For correspondence: y.jia@murdoch.edu.au c.li@murdoch.edu.au wlwang@cc.ncue.edu.tw
Gangxu Shen
2School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan
3National Changhua University of Education, Changhua, Taiwan
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Stephanie Nguyen
4Institute of Photonics and Advanced Sensing (IPAS), School of Biological Sciences, University of Adelaide, Adelaide 5005, Australia
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Yujuan Zhang
1College of Science, Health, Engineering and Education, Murdoch University, Murdoch, WA, 6150, Australia
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Keng-Shiang Huang
2School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan
5College of Medicine, I-Shou University, Kaohsiung, Taiwan
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Hsing-Ying Ho
6Guo-Yuan Clinic, Taichung, Taiwan
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Wei-Shio Hor
7TOPO Pharmaceutical Co., Ltd, Taichung, Taiwan
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Chih-Hui Yang
5College of Medicine, I-Shou University, Kaohsiung, Taiwan
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John B Bruning
4Institute of Photonics and Advanced Sensing (IPAS), School of Biological Sciences, University of Adelaide, Adelaide 5005, Australia
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Chengdao Li
1College of Science, Health, Engineering and Education, Murdoch University, Murdoch, WA, 6150, Australia
8Department of Primary Industry and Regional Development, Government of Western Australia, South Perth, WA, 6155, Australia
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  • For correspondence: y.jia@murdoch.edu.au c.li@murdoch.edu.au wlwang@cc.ncue.edu.tw
Wei-Lung Wang
3National Changhua University of Education, Changhua, Taiwan
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  • For correspondence: y.jia@murdoch.edu.au c.li@murdoch.edu.au wlwang@cc.ncue.edu.tw
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Summary

Monitoring the mutation dynamics of SARS-CoV-2 is critical for the development of effective approaches to contain the pathogen. By analyzing 106 SARS-CoV-2 and 39 SARS genome sequences, we provided direct genetic evidence that SARS-CoV-2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a receptor binding domain mutation that leads to weaker ACE2 binding capability based on in silico simulation, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. This represents the first report of a significant SARS-CoV-2 mutant, and requires attention from researchers working on vaccine development around the world.

Highlights

  • Based on the currently available genome sequence data, we provided direct genetic evidence that the SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002-2003 outbreak.

  • The spike (S) protein encoding gene of SARS-COV-2 is found relatively more conserved than other protein-encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development.

  • Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history.

  • We confirmed a previously reported rearrangement in the S protein arrangement of SARS-COV-2, and propose that this rearrangement should have occurred between human SARS-CoV and a bat SARS-CoV, at a time point much earlier before SARS-COV-2 transmission to human.

  • We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ORCID added for one author

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 19, 2021.
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Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity
Yong Jia, Gangxu Shen, Stephanie Nguyen, Yujuan Zhang, Keng-Shiang Huang, Hsing-Ying Ho, Wei-Shio Hor, Chih-Hui Yang, John B Bruning, Chengdao Li, Wei-Lung Wang
bioRxiv 2020.04.09.034942; doi: https://doi.org/10.1101/2020.04.09.034942
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Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity
Yong Jia, Gangxu Shen, Stephanie Nguyen, Yujuan Zhang, Keng-Shiang Huang, Hsing-Ying Ho, Wei-Shio Hor, Chih-Hui Yang, John B Bruning, Chengdao Li, Wei-Lung Wang
bioRxiv 2020.04.09.034942; doi: https://doi.org/10.1101/2020.04.09.034942

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