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Short Report
The emergence of SARS-CoV-2 by an unusual genome reconstitution
Seong-Tshool Hong
1. Department of Biomedical Sciences and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Jeonbuk 54907, South Korea.
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
SARS-CoV-2 has been spreading remarkedly fast around the world since its emergence while the origin of the virus remains ambiguous. Here, we constructed all of the original prototype genome sequences of SARS-CoV-2 by selecting the common nucleotide among the different virus strains with species. Phylogenetic analysis on the prototype sequences showed that SARS-CoV-2 was a direct descendant of Bat-CoV and was closely related to Pan-CoV, Bat-SL-CoV, and SARS-CoV. The pairwise comparison of SARS-CoV-2 with Bat-CoV showed an unusual replacement of the motif consisting of 7 amino acids within the spike protein of SARS-CoV-2. Database searches showed that the motif originated from a surface protein of Plasmodium malariae, suggesting that the SARS-CoV-2 was emerged after acquiring the motif of the malaria surface protein.
Keywords
SARS-CoV-2, prototype, genome, phylogenetic analysis.
Figure 1
Figure 2
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Andras Szilagyi
commented on 07 June, 2020
The conclusion of this article is false. The short sequence in question (NNLDSKV) in SARS-CoV-2 is actually identical to that in the pangolin coronavirus, and it also has 2 (3) identical residues in the RaTG13 coronavirus (RsSHC014 coronavirus), so it is not a 7-residue consecutive mutation. Too bad that the authors do not show the sequence alignments because then the reader would immediately see that the claim of the authors is false. Also, the NNLDSKV sequence can be found in at least 100 proteins from a wide range of organisms including bacteria, plants, and animals (this can be checked by e.g. the Peptide Match server of PIR), so contrary to the authors' claim it is not specific to P. malariae. In addition, (hydroxy)chloroquine is a wide-spectrum antiviral which is effective against several different viruses including HIV, flaviviruses and other coronaviruses, thus its effect is not specific to SARS-CoV-2, and has nothing to do with the presence of the NNLDSKV sequence. In summary, this article contains several serious errors and flaws, and its conclusions are invalid.
View 3 replies
Mary Olsen
commented on 07 June, 2020
You are right. The commenter did not understand the manuscript. Fig 1 clearly showed sequence alignments.
View 1 reply
Andras Szilagyi
replied on 08 June, 2020
Fig 1 does not contain a sequence alignment.
Perez
commented on 08 June, 2020
They are right See &7 in perez, j., & Montagnier, L. (2020, April 25). COVID-19, SARS and Bats Coronaviruses Genomes Unexpected Exogeneous RNA Sequences. https://doi.org/10.31219/osf.io/d9e5g
Perez
commented on 08 June, 2020
This plasmodium inserts are trouve. Please see &7 in perez, j., & Montagnier, L. (2020, April 25). COVID-19, SARS and Bats Coronaviruses Genomes Unexpected Exogeneous RNA Sequences. https://doi.org/10.31219/osf.io/d9e5g
John F.Signus
commented on 08 February, 2021
https://zenodo.org/record/4450267#.YCFj7yQ3uEf Issue with NNLDSKV. All datasets containing the MP789 sequence have human sequences in it. Sequences that don’t have human in it don’t have fragments of MP789. So the idea of a pangolin RBD/RBM for NNLDSKV is false. Because it was really one of the two grant viruses (https://archive.is/D3db3) of the WIV, being studied in Humanized Mice, accidentally entering the samples that were stored together in the Chinese National Gene Bank (CNGB). Rack contamination or even intentional experimental inoculation is possible.
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This is a preprint. It has not completed peer review.
Short Report
The emergence of SARS-CoV-2 by an unusual genome reconstitution
Seong-Tshool Hong
1. Department of Biomedical Sciences and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Jeonbuk 54907, South Korea.
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 05 Jun, 2020
Community comments: 12
Metrics
Comments: 12
PDF Downloads: ...
HTML Views: ...
Subject Areas
Bioinformatics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
SARS-CoV-2 has been spreading remarkedly fast around the world since its emergence while the origin of the virus remains ambiguous. Here, we constructed all of the original prototype genome sequences of SARS-CoV-2 by selecting the common nucleotide among the different virus strains with species. Phylogenetic analysis on the prototype sequences showed that SARS-CoV-2 was a direct descendant of Bat-CoV and was closely related to Pan-CoV, Bat-SL-CoV, and SARS-CoV. The pairwise comparison of SARS-CoV-2 with Bat-CoV showed an unusual replacement of the motif consisting of 7 amino acids within the spike protein of SARS-CoV-2. Database searches showed that the motif originated from a surface protein of Plasmodium malariae, suggesting that the SARS-CoV-2 was emerged after acquiring the motif of the malaria surface protein.
Figure 1
Figure 2
Andras Szilagyi
commented on 07 June, 2020
The conclusion of this article is false. The short sequence in question (NNLDSKV) in SARS-CoV-2 is actually identical to that in the pangolin coronavirus, and it also has 2 (3) identical residues in the RaTG13 coronavirus (RsSHC014 coronavirus), so it is not a 7-residue consecutive mutation. Too bad that the authors do not show the sequence alignments because then the reader would immediately see that the claim of the authors is false. Also, the NNLDSKV sequence can be found in at least 100 proteins from a wide range of organisms including bacteria, plants, and animals (this can be checked by e.g. the Peptide Match server of PIR), so contrary to the authors' claim it is not specific to P. malariae. In addition, (hydroxy)chloroquine is a wide-spectrum antiviral which is effective against several different viruses including HIV, flaviviruses and other coronaviruses, thus its effect is not specific to SARS-CoV-2, and has nothing to do with the presence of the NNLDSKV sequence. In summary, this article contains several serious errors and flaws, and its conclusions are invalid.
View 3 replies
Seong-Tshool Hong
replied on 07 June, 2020
The 7-aa motif (NNLDSKV ) is not present in pangolin CoV and Plant and not in 100 proteins. I am not quite sure whether you searched database correctly. However, the same motif is present in some bacteria. Also we did not say that the motif is specific to P. malariae. All we said was the motif is also present in P. malariae. I think you over-and mis-interpreted the paper.
View 1 reply
Andras Szilagyi
replied on 08 June, 2020
Yes, the pangolin CoV does contain the NNLDSKV motif. See Fig. 5 in https://pubs.acs.org/doi/10.1021/acs.jproteome.0c00129 or Fig. 3 in https://www.sciencedirect.com/science/article/pii/S0960982220303602 or Fig. 3 in https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008421 (published articles). Like I indicated, I ran the Peptide Match server at https://research.bioinformatics.udel.edu/peptidematch/index.jsp with the NNLDSKV sequence, and it hits 101 proteins, 63 from bacteria, 11 from plants, 9 from animals, etc.
Oluvan
replied on 09 June, 2020
The “ pangolin” sequence came from samples with human derived contamination in it. Up to 17% on Trace. Look up the SRA and see if you can correlate the virus reads to the first animal traced on the result.
View 1 reply
Andras Szilagyi
replied on 09 June, 2020
Too little information. Please provide links to database records and analyses to back up your claim.
View 1 reply
Oluvan
replied on 08 July, 2020
https://www.ncbi.nlm.nih.gov/bioproject/PRJNA573298 Which was where the raw sequences came from. See it with your own eyes.
Shannon
replied on 08 August, 2020
The preponderance of evidence is that an ancestral virus jumped from bats to pangolin and it is an offshoot otherwise unrelated to SARS-2. The exploitation of furin cleavage is the hot-spot to research right now. No other β-CoV has this feature. Mouse Hepatitis and Infectious Bronchitis virus are the closest ones.
Mary Olsen
commented on 07 June, 2020
You are right. The commenter did not understand the manuscript. Fig 1 clearly showed sequence alignments.
View 1 reply
Andras Szilagyi
replied on 08 June, 2020
Fig 1 does not contain a sequence alignment.
Perez
commented on 08 June, 2020
They are right See &7 in perez, j., & Montagnier, L. (2020, April 25). COVID-19, SARS and Bats Coronaviruses Genomes Unexpected Exogeneous RNA Sequences. https://doi.org/10.31219/osf.io/d9e5g
Perez
commented on 08 June, 2020
This plasmodium inserts are trouve. Please see &7 in perez, j., & Montagnier, L. (2020, April 25). COVID-19, SARS and Bats Coronaviruses Genomes Unexpected Exogeneous RNA Sequences. https://doi.org/10.31219/osf.io/d9e5g
John F.Signus
commented on 08 February, 2021
https://zenodo.org/record/4450267#.YCFj7yQ3uEf Issue with NNLDSKV. All datasets containing the MP789 sequence have human sequences in it. Sequences that don’t have human in it don’t have fragments of MP789. So the idea of a pangolin RBD/RBM for NNLDSKV is false. Because it was really one of the two grant viruses (https://archive.is/D3db3) of the WIV, being studied in Humanized Mice, accidentally entering the samples that were stored together in the Chinese National Gene Bank (CNGB). Rack contamination or even intentional experimental inoculation is possible.
Seong-Tshool Hong
replied on 07 June, 2020
The 7-aa motif (NNLDSKV ) is not present in pangolin CoV and Plant and not in 100 proteins. I am not quite sure whether you searched database correctly. However, the same motif is present in some bacteria. Also we did not say that the motif is specific to P. malariae. All we said was the motif is also present in P. malariae. I think you over-and mis-interpreted the paper.
View 1 reply
Andras Szilagyi
replied on 08 June, 2020
Yes, the pangolin CoV does contain the NNLDSKV motif. See Fig. 5 in https://pubs.acs.org/doi/10.1021/acs.jproteome.0c00129 or Fig. 3 in https://www.sciencedirect.com/science/article/pii/S0960982220303602 or Fig. 3 in https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008421 (published articles). Like I indicated, I ran the Peptide Match server at https://research.bioinformatics.udel.edu/peptidematch/index.jsp with the NNLDSKV sequence, and it hits 101 proteins, 63 from bacteria, 11 from plants, 9 from animals, etc.
Oluvan
replied on 09 June, 2020
The “ pangolin” sequence came from samples with human derived contamination in it. Up to 17% on Trace. Look up the SRA and see if you can correlate the virus reads to the first animal traced on the result.
View 1 reply
Andras Szilagyi
replied on 09 June, 2020
Too little information. Please provide links to database records and analyses to back up your claim.
View 1 reply
Oluvan
replied on 08 July, 2020
https://www.ncbi.nlm.nih.gov/bioproject/PRJNA573298 Which was where the raw sequences came from. See it with your own eyes.
Shannon
replied on 08 August, 2020
The preponderance of evidence is that an ancestral virus jumped from bats to pangolin and it is an offshoot otherwise unrelated to SARS-2. The exploitation of furin cleavage is the hot-spot to research right now. No other β-CoV has this feature. Mouse Hepatitis and Infectious Bronchitis virus are the closest ones.