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I have been a tenured academic (Senior Lecturer) within the School of Pharmacy and Applied Science at La Trobe University, Australia teaching and researching in the areas of phage therapy (bacterial virology), pharmacy, environmental microbiology, bioinformatics and cancer.
"""
Since that seems easy enough to look up and call him out on if he were lying, I am inclined to believe that it's true.
I am inclined to believe his take on things over yours, given that the only info I can see immediately about you is your info blurb stating, "Damn kids, get off my lawn."
That said, I don't think anyone is treating what he says as gospel. But it's an interesting perspective.
At the risk of starting a flame war, lvs is mostly correct.
These are NOT whole gene deletions, they are nucleotide deletions. Genes are usually longer than 33 nucleotides, by my count the largest deletion he sees. For reference, that’s 11 amino acids, rule of thumb for an average protein length is about 200 amino acids.
The author highlights that many of these deletions are not codon aligned, which means that if you make this mutation, the resulting protein is highly unlikely to be translated properly. This is true, however devoid of context.
Most of the mutations are very rare. The highest frequency one occurs 400 or so out of at minimum 10,000 examples. Next one is 36/10,000. It’s possible these matter, it’s also possible these viral sequences are just low quality and the mutations are an artifact. It’s also possible that these mutations don’t actually matter to viral function for whatever reason. For example, if the mutation is at the end of a protein, it could screw up everything downstream but the protein before the mutation works just fine, i.e. mutation doesn’t matter. It’s just hard to tell with the data in this article.
The concept that maybe there are attenuated strains isn’t completely bogus, there is some thought a Singapore strain (with a massive deletion of 380 nucleotides, or 10x what we see here [1]) might be less infective. This is speculation and we don’t know yet, but that sounds maybe possible to me as a PhD Biochemist (if we’re gonna get all credential-spreading here).
However saying “The really interesting deletion mutations are those in the non-structural accessory genes. These are the genes that are likely to play an important role in pathogenicity and it would be expected that some of these mutations may make the virus less dangerous (attenuated).” Is really pushing it. I don’t know of any science to believe this one way or another, viruses are pathogenic for a variety of reasons, both accessory and core (whatever that means) proteins matter.
In short, given the uncertainty, we can hope there’s a less infectious strain out there, but this article provides precious little evidence to that effect.
Lvs is mostly wrong. I am not claiming any of these mutant strains are attenuated, I am saying that deletion mutants exists and we should investigate them to see if they are attenuated.
I am not providing evidence that an attenuated strain exists, just evidence that it could exist because the right type of mutations are found in SARS-CoV-2. The only way we are going to find out if there are attenuated strains is to look for them which as far as I know nobody is trying.
So let's remember how evolution works, shall we? Evolution selects for strains that reproduce the most and selects against ones with attenuated reproduction rates. That's the whole basis of biology. If you've observed a wild strain sequenced in a database, that should be considered direct evidence that it reproduces well enough to have been sampled as a representative isolate.
> as far as I know nobody is trying
Of course we are. We are deeply engaged in studying the key residues that mediate all aspects of viral infection, reproduction, and clinical pathology. That's another way of saying that an incredible number of researchers have dropped everything to study the genetic and molecular determinants of pathogenicity. Don't worry -- we are on it.
> we can hope there’s a less infectious strain out there
But how? We are able to surveil only a tiny fraction of genomes, relative to strains circulating. How would a "less infectious strain" ever emerge to the extent we'd have a high probability of sampling it? Darwin argues against this version of the idea.
Nevertheless, the OP is also wrong that it's faster to produce a live attenuated vaccine by finding one in the wild than it is to use tried-and-true viral vectors that are easy to reengineer, have previously received regulatory approval, and indeed are already in active trials (e.g. Oxford's adenoviral trial). It's also easier to trial heat-killed virus -- and indeed, that too is being trialed.
We can actually sample quite a large percentage of the strains out there if we actually try. COG-UK has already sampled 10,000 out of the few 100,000s in the UK without really trying.
Can you please stop saying I am arguing for things I am not arguing for? More time spent reading and less posting would improve your argument.
Yes, there are about 13k genomes deposited in the databses right now, but they are from all over the world -- not just the UK.
But yes, given infinite capacity it would be excellent to sequence from every single patient. It would be a dream, but sadly we're barely able to get enough cotton swabs and RNA isolation kits right now to run a basic qPCR for 10% of the population, let alone get all those viral genome sequences. It would be fascinating to have that many, of course.
You do realise that there are over a million positive samples sitting in freezers in the USA alone. You do know that a single modern DNA sequencing instruments can sequence more than 500,000 viral genomes in one 48 hour run?
It’s my understanding that viruses have a complex fitness function. If you think about it, the ideal virus spreads like crazy but doesn’t make anyone sick. If you make someone sick, you reduce the time they spend in the world so you spread less. Killing the host is definitely a no-no from the viral perspective, now you spread dramatically less. So viruses actually tend to evolve toward less intense disease. It’s why novel viruses kill so much more than viruses that have been around in the human population for a long time.
Forced evolution to lower infectivity is also a common way to make vaccines, so I’m quite certain one of the 100 or so vaccine efforts is trying this.
However, it’s not clear that the deletions in the OP are attenuating. If we end up with attenuated virus, it will likely come from a directed evolution experiment, not just getting lucky with a natural strain. Even such a natural strain would likely need to go through a fair bit of directed evolution to attenuated it to the point of harmlessness.
We don’t know if the deletions already seen in the current genome data set are attenuated or not as nobody has checked. I am suggesting that we check.
The bigger point I was making is that there are many deletion mutants out there. We should be looking for more and checking if they are attenuated or not. We might be very unlucky and find there are none, but that seems rather defeatist given we haven’t even tried.
I don’t know. It is a novel idea as it wasn’t possible more than 10 years ago to search. My personal experience is new ideas struggle to get any support until they are shown to be correct and then everyone says it was always obvious.
I don't know enough about any of it to consider arguments.
I apologize for the probably overly snarky comment. I woke up in the middle of the night and was having a hard time falling back to sleep.
I really wouldn't be surprised if the two of you are in more agreement than either of you realize. "Violent agreement" as I've sometimes heard it called.
Also for the record, I didn't downvote you. Just provided my response of why I was inclined to believe the author over you.
""" I have been a tenured academic (Senior Lecturer) within the School of Pharmacy and Applied Science at La Trobe University, Australia teaching and researching in the areas of phage therapy (bacterial virology), pharmacy, environmental microbiology, bioinformatics and cancer. """
Since that seems easy enough to look up and call him out on if he were lying, I am inclined to believe that it's true.
I am inclined to believe his take on things over yours, given that the only info I can see immediately about you is your info blurb stating, "Damn kids, get off my lawn."
That said, I don't think anyone is treating what he says as gospel. But it's an interesting perspective.