Early Wuhan Coronavirus: 3 Extra Mutations Discovered

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In summary: The Wang et al article that was tweeted is a 2019 article that discusses the mutations in the early SARS-CoV-2 sequences. The article was published in 2020, but was removed by the submitting investigator in June 2020. The article discusses the L and S types of SARS-CoV-2 and the classification of 50 NTS positive samples. The article also discusses the possibility that Huanan is not the origin of the SARS-CoV-2 pandemic.
  • #1
Tom.G
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The early partial sequences were posted to National Institutes of Health in March 2020, and removed at the request of the submitting investigator in June 2020.
... those [Wuhan] market viruses actually have three extra mutations that are missing from SARS-CoV-2 samples collected weeks later. In other words, those later viruses look more like coronaviruses found in bats, supporting the idea that there was some early lineage of the virus that did not pass through the seafood market.

https://www.nytimes.com/2021/06/23/science/coronavirus-sequences.html
[edit:]Which is a rewrite of:
https://www.livescience.com/deleted-covid-19-gene-sequences-found.html
[/edit]

There are several links in the article for further information.
https://www.biorxiv.org/content/10.1101/2021.06.18.449051v1
https://peerj.com/articles/9255/#supplementary-material
https://trace.ncbi.nlm.nih.gov/Traces/sra/
https://www.medrxiv.org/content/10.1101/2020.03.04.20029538v1.full-text
https://onlinelibrary.wiley.com/doi/full/10.1002/smll.202002169

Cheers,
Tom
 
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  • #2
As pointed out in a tweet by Stephen Goldstein, the original article by Wang et al (2020) https://onlinelibrary.wiley.com/doi/full/10.1002/smll.202002169 has been available since August 2020, and explicitly lists the key mutations in Table 1.

Wang et al also explicitly discuss "Tang et al. (2020) have found that SARS-CoV-2 genomes evolved into two major types (designated L and S) that are well defined by two different SNPs at position 8782 (T8782C, synonymous) and 28144 (T28144C, Leu→Ser).[37] Based on the classification of 50 NTS positive samples (Experimental Section), 31 samples had a ≥10× depth at position 28144 (Table S5, Supporting Information), of which 22 (71.0%) were classified as L type, 8 (25.8%) were classified as S type, and one (3.2%) was uncertain (Figure 7c). These results were consistent with those previously reported,[37] which indicated that the L type was more prevalent in the early stages of the outbreak in Wuhan."

The nomenclature used by Wang et al about L and S types is slightly different from that used by Rambaut et al (2020) https://www.nature.com/articles/s41564-020-0770-5. However, the S and L seem to map onto Rambaut's A and B respectively.

Rambaut had already commented that "Hence, although viruses from lineage B happen to have been sequenced and published first, it is likely (based on current data) that the most recent common ancestor (MRCA) of the SARS-CoV-2 phylogeny shares the same genome sequence as the early lineage A sequences (for example, Wuhan/WH04/2020)."

As noted by Robert Garry, from the WHO report, it seems that the Huanan market genomes are to date mainly from lineage B.

It is uncertain whether Rambaut et al's conjecture that lineage A is earlier is correct. But it points to extant data already suggesting scenarios in which Huanan is not the origin.

Further, as acknowledged by Bloom, one of the progenitors he suggests had already been suggested by Kumar et al (2021) by different methods. Kumar et al suggest "This progenitor genome differs from genomes of the first coronaviruses sampled in China by three variants, implying that none of the earliest patients represent the index case or gave rise to all the human infections."
 
  • #3
BTW, the thread title says earlier (November 2019) partial sequences found. The "recovered" sequences are thought to be from January 2020.

https://onlinelibrary.wiley.com/doi/full/10.1002/smll.202002169
"The samples were divided into two groups: i) 45 nasopharyngeal swabs from outpatients with suspected COVID-19 early in the epidemic (January 2020) ..."
 
  • #4
The "November 2019" date came from:
https://www.livescience.com/deleted-covid-19-gene-sequences-found.html
However, cases from early December and as far back as November 2019 had no ties to the market, indicating pretty early in the pandemic that the virus emerged from another spot.

The NYTIMES article seems to be an (incomplete) rewrite of the LIVESCIENCE article.

LIVESCIENCE link added to OP.

Cheers,
Tom
 
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  • #5
Earlier clusters and trying to figure out the relative importance of various markets or other places of early transmission will definitely be worth investigating further. The WHO report itself says:

"... but whereas the data provided no evidence for substantial SARS-CoV-2 transmission in the months preceding the outbreak in December 2019, sporadic transmission or minor clusters of SARS-CoV-2 cannot be ruled out."

"Many of the early cases were associated with the Huanan market, but a similar number of cases were associated with other markets and some were not associated with any markets. Transmission within the wider community in December could account for cases not associated with the Huanan market which, together with the presence of early cases not associated with that market, could suggest that the Huanan market was not the original source of the outbreak."

"Other milder cases that were not identified, however, could provide the link between the Huanan Market and early cases without an apparent link to the market. No firm conclusion therefore about the role of the Huanan Market can be drawn."
 
  • #6
Bloom's technical conclusion about a possible SARS-CoV-2 progenitor is "Second, given current data, there are two plausible identities for the progenitor of all known SARS-CoV-2. One is proCoV2 described by Kumar et al.(2021), and the other is a sequence that carries three mutations (C8782T, T28144C, and C29095T) relative to Wuhan-Hu-1."

As Bloom notes, C29095T is carried by the "recovered" data as well as by existing sequences from Wuhan-infected patients hospitalized in Guangdong. In terms of data processing, Bloom "recovered" data and also improved the annotation of sequences previously known to him. So it would be interesting to know whether the technical conclusion could have been reached with only the latter processing step.
 

Related to Early Wuhan Coronavirus: 3 Extra Mutations Discovered

1. What are the extra mutations discovered in the early Wuhan coronavirus?

The three extra mutations that have been discovered in the early Wuhan coronavirus are D614G, N501Y, and P681H. These mutations are located on the spike protein of the virus, which is responsible for attaching to and infecting human cells.

2. How do these mutations affect the virus?

The D614G mutation has been found to make the virus more infectious and easier to spread. The N501Y mutation may make the virus more resistant to certain treatments and vaccines. The P681H mutation may also increase the virus's ability to infect cells.

3. Where did these mutations come from?

It is believed that these mutations occurred naturally as the virus spread and replicated in human hosts. However, there is also a possibility that they may have originated in an animal host before being transmitted to humans.

4. Are these mutations cause for concern?

While these mutations may make the virus more transmissible and potentially more resistant to treatments, it is important to note that viruses naturally mutate over time. However, continued monitoring of these mutations is necessary to understand their impact on the virus and its spread.

5. Will the current vaccines be effective against these mutations?

There is not enough information yet to determine the effectiveness of current vaccines against these specific mutations. However, many experts believe that the vaccines should still provide some level of protection against the virus and its variants, including those with these mutations.

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