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"Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag" https://biorxiv-cache.s3-us-west-2.amazonaws.com/2020.01.30.927871

"Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag" https://biorxiv-cache.s3-us-west-2.amazonaws.com/2020.01.30.927871.full.pdf https://biorxiv-cache.s3-us-west-2.amazonaws.com/2020.01.30.... > [ABSTRACT] We are currently witnessing a major epidemic caused by the 2019 novel coronavirus (2019-nCoV). The evolution of 2019-nCoV remains elusive. We found 4 insertions in the spike glycoprotein (S) which are unique to the 2019-nCoV and are not present in other coronaviruses. Importantly, amino acid residues in all the 4 inserts have identity or similarity to those in the HIV1 gp120 or HIV-1 Gag. Interestingly, despite the inserts being discontinuous on the primary amino acid sequence, 3D-modelling of the 2019-nCoV suggests that they converge to constitute the receptor binding site. The finding of 4 unique inserts in the 2019-nCoV, all of which have identity /similarity to amino acid residues in key structural proteins of HIV-1 is unlikely to be fortuitous in nature. This work provides yet unknown insights on 2019-nCoV and sheds light on the evolution and pathogenicity of this virus with important implications for diagnosis of this virus.

zozbot234 7y ago
FWIW, https://old.reddit.com/user/BurrShotFirst1804 https://old.reddit.com/user/BurrShotFirst1804 is claiming that this (preprint, unreviewed) paper is very misleading, speaking as (supposedly) someone highly familiar with at least one of these HIV proteins. Not sure what to make of either the paper itself or this response to it.
- m_alexgr 7y ago
  Difficult to properly peer review when things are moving so quickly.
  - Fomite 7y ago
    Plenty of things are being peer reviewed properly with this outbreak. But you can't take preprints in biology as any more holy writ than you can the occasional post on arXiv where someone claims to have come up with a complete unified model for physics, or solved a previously intractable problem.
    - m_alexgr 7y ago
      True about the complete theory. I would suggest that proper review takes time though. Many eyes.
- rococode 7y ago
  Copying /u/BurrShotFirst1804's main response here for easier reference: ===== This study is crap. My comment from another thread. This paper isn't peer reviewed or published. It's just an online journal. I've worked pretty closely with gag in my PhD thesis. Gag is the conglomerate protein that gets cut by the protease to generate the hiv capsid, matrix, and carrier proteins. Gp120 is the receptor protein. This is a really fucking dumb study and these scientists should be ashamed. Those amino acids are so short. They just went and looked for a virus to match. You can go and blast the amino acids yourself. Just copy and paste from the journal entry into NCBIs BLASTp. I did it and there's hundreds of matches to those sequences. HIV didn't even come up in the first 100. The 4th residue is missing like 6 amino acids. There are conserved regions in viruses. Their "gp120" match compares 6 amino acids out of 850 in the whole protein for example. They found 4 sections that were in the new virus but not SARS. They then took these differences and ran them against all known viral proteins. They only looked at proteins with 100% matches, but if you look at the table they didn't match 100% for alignment. So like one is ABCEFG and they match it to an HIV protein that is ABCXYZEFG and they are calling those total matches. There's also tons of viruses that match these tiny sequences, they just noticed all 4 have HIV matches so they ignore the other matches and only looked at HIV. Go blast it yourself if you want.
  - dekhn 7y ago
    A significant part of my postdoc training involved carefully determining what BLAST hits are likely to be true or not. However, I saw some scientists (often bored, or inexperienced) who would set their E-value threshold to 10 (IE, expect 9 false positives for every true positive) and just sort of mine the results until they had some other data that seemed "significant" and published. A lot of science is done this way :(
  - flycaliguy 7y ago
    I’m think they might be aiming at HIV because China has also been in the news for genetically modifying two babies to prevent HIV. Disinformation designed to send people down a hole, linking stuff together to make it seem more plausible.
chiefalchemist 7y ago
Can someone translate this?
- coolspot 7y ago
  Parts of 2019-nCoV are similar to Human Immunodeficiency Virus . [HIV] - https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV [gp120] - https://en.wikipedia.org/wiki/Gp120 https://en.wikipedia.org/wiki/Gp120
gravelc 7y ago
This is laughable. Table 1 shows four alignments. The first two are only six contiguous residues, so can easily happen by chance. Three has multiple mistmatches as well as the gap (red). Four has an even larger gap to get the alignment. Take any two viruses and there's a decent likelihood of finding similar alignments.
- KaoruAoiShiho 7y ago
  Thanks honestly reassuring. - Some layman.
  - dylz 7y ago
    They don't appear to even be matching entire sequences. An analogy might be "these two web pages both contain <div>*</div>! oh no!" while completely disregarding everything in the middle.
    - KaoruAoiShiho 7y ago
      If it's as bad as it sounds, would this be a neophyte mistake or deliberate conspiracy mongering?
      - dekhn 7y ago
        Based on my read, it's inexperienced bioinformaticists.
      - dylz 7y ago
        I don't know, nor am I in a position to really have an opinion on this, but it might even be as small of a reason as "hey I want to get published" The PDF itself is MS Word, has numerous typos/little care (words like 'alingment'), random font changes back and forth between Times New Roman and the default MS Word font (Calibri?)) For HIV related fearmongering about "well, why would they know to treat it with HIV meds??", people are looking at this already because previous SARS-CoV has previous investigation with HIV medication, it is not unique to nCOV: https://www.ncbi.nlm.nih.gov/pubmed/14985565 https://www.ncbi.nlm.nih.gov/pubmed/14985565, https://www.ncbi.nlm.nih.gov/pubmed/15144898 https://www.ncbi.nlm.nih.gov/pubmed/15144898, https://www.ncbi.nlm.nih.gov/pubmed/14519691 https://www.ncbi.nlm.nih.gov/pubmed/14519691 - these are from 2003-2006.
LoSboccacc 7y ago
and China is testing HIV related drugs for treatment since well before this paper came out https://www.news.com.au/lifestyle/health/health-problems/china-tests-hiv-drug-for-treatment-of-coronavirus-symptoms/news-story/f794bca13f4cfcb9798f9dc2de63beb5#.u5nqy https://www.news.com.au/lifestyle/health/health-problems/chi... but it's just a lucky hunch, right? not like they would try to hide knowing more about it, right?
- dylz 7y ago
  It was done for other coronavirus: https://www.ncbi.nlm.nih.gov/pubmed/15144898 https://www.ncbi.nlm.nih.gov/pubmed/15144898
  - LoSboccacc 7y ago
    so it's a string of random hunches, all rotating around novel Chinese viruses and hiv damn they're lucky!
gkarthik92 7y ago
A simple BLAST search of those inserts shows matches to MANY different organisms. No reason to conclude HIV.
justinzollars 7y ago
This paper is not yet peer reviewed. I'm sure this claim will be studied exhaustively in the coming days/weeks.

zozbot234 7y ago

FWIW, https://old.reddit.com/user/BurrShotFirst1804 https://old.reddit.com/user/BurrShotFirst1804 is claiming that this (preprint, unreviewed) paper is very misleading, speaking as (supposedly) someone highly familiar with at least one of these HIV proteins. Not sure what to make of either the paper itself or this response to it.

m_alexgr 7y ago
Difficult to properly peer review when things are moving so quickly.
- Fomite 7y ago
  Plenty of things are being peer reviewed properly with this outbreak. But you can't take preprints in biology as any more holy writ than you can the occasional post on arXiv where someone claims to have come up with a complete unified model for physics, or solved a previously intractable problem.
  - m_alexgr 7y ago
    True about the complete theory. I would suggest that proper review takes time though. Many eyes.
rococode 7y ago
Copying /u/BurrShotFirst1804's main response here for easier reference: ===== This study is crap. My comment from another thread. This paper isn't peer reviewed or published. It's just an online journal. I've worked pretty closely with gag in my PhD thesis. Gag is the conglomerate protein that gets cut by the protease to generate the hiv capsid, matrix, and carrier proteins. Gp120 is the receptor protein. This is a really fucking dumb study and these scientists should be ashamed. Those amino acids are so short. They just went and looked for a virus to match. You can go and blast the amino acids yourself. Just copy and paste from the journal entry into NCBIs BLASTp. I did it and there's hundreds of matches to those sequences. HIV didn't even come up in the first 100. The 4th residue is missing like 6 amino acids. There are conserved regions in viruses. Their "gp120" match compares 6 amino acids out of 850 in the whole protein for example. They found 4 sections that were in the new virus but not SARS. They then took these differences and ran them against all known viral proteins. They only looked at proteins with 100% matches, but if you look at the table they didn't match 100% for alignment. So like one is ABCEFG and they match it to an HIV protein that is ABCXYZEFG and they are calling those total matches. There's also tons of viruses that match these tiny sequences, they just noticed all 4 have HIV matches so they ignore the other matches and only looked at HIV. Go blast it yourself if you want.
- dekhn 7y ago
  A significant part of my postdoc training involved carefully determining what BLAST hits are likely to be true or not. However, I saw some scientists (often bored, or inexperienced) who would set their E-value threshold to 10 (IE, expect 9 false positives for every true positive) and just sort of mine the results until they had some other data that seemed "significant" and published. A lot of science is done this way :(
- flycaliguy 7y ago
  I’m think they might be aiming at HIV because China has also been in the news for genetically modifying two babies to prevent HIV. Disinformation designed to send people down a hole, linking stuff together to make it seem more plausible.

chiefalchemist 7y ago

Can someone translate this?

coolspot 7y ago
Parts of 2019-nCoV are similar to Human Immunodeficiency Virus . [HIV] - https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV [gp120] - https://en.wikipedia.org/wiki/Gp120 https://en.wikipedia.org/wiki/Gp120

gravelc 7y ago

This is laughable. Table 1 shows four alignments. The first two are only six contiguous residues, so can easily happen by chance. Three has multiple mistmatches as well as the gap (red). Four has an even larger gap to get the alignment. Take any two viruses and there's a decent likelihood of finding similar alignments.

KaoruAoiShiho 7y ago
Thanks honestly reassuring. - Some layman.
- dylz 7y ago
  They don't appear to even be matching entire sequences. An analogy might be "these two web pages both contain <div>*</div>! oh no!" while completely disregarding everything in the middle.
  - KaoruAoiShiho 7y ago
    If it's as bad as it sounds, would this be a neophyte mistake or deliberate conspiracy mongering?
    - dekhn 7y ago
      Based on my read, it's inexperienced bioinformaticists.
    - dylz 7y ago
      I don't know, nor am I in a position to really have an opinion on this, but it might even be as small of a reason as "hey I want to get published" The PDF itself is MS Word, has numerous typos/little care (words like 'alingment'), random font changes back and forth between Times New Roman and the default MS Word font (Calibri?)) For HIV related fearmongering about "well, why would they know to treat it with HIV meds??", people are looking at this already because previous SARS-CoV has previous investigation with HIV medication, it is not unique to nCOV: https://www.ncbi.nlm.nih.gov/pubmed/14985565 https://www.ncbi.nlm.nih.gov/pubmed/14985565, https://www.ncbi.nlm.nih.gov/pubmed/15144898 https://www.ncbi.nlm.nih.gov/pubmed/15144898, https://www.ncbi.nlm.nih.gov/pubmed/14519691 https://www.ncbi.nlm.nih.gov/pubmed/14519691 - these are from 2003-2006.

LoSboccacc 7y ago

and China is testing HIV related drugs for treatment since well before this paper came out https://www.news.com.au/lifestyle/health/health-problems/china-tests-hiv-drug-for-treatment-of-coronavirus-symptoms/news-story/f794bca13f4cfcb9798f9dc2de63beb5#.u5nqy https://www.news.com.au/lifestyle/health/health-problems/chi... but it's just a lucky hunch, right? not like they would try to hide knowing more about it, right?

dylz 7y ago
It was done for other coronavirus: https://www.ncbi.nlm.nih.gov/pubmed/15144898 https://www.ncbi.nlm.nih.gov/pubmed/15144898
- LoSboccacc 7y ago
  so it's a string of random hunches, all rotating around novel Chinese viruses and hiv damn they're lucky!

gkarthik92 7y ago

A simple BLAST search of those inserts shows matches to MANY different organisms. No reason to conclude HIV.

justinzollars 7y ago

This paper is not yet peer reviewed. I'm sure this claim will be studied exhaustively in the coming days/weeks.