when the R0 goes up is that due to changes in the spike protein that increase binding affinity with the ACE2 receptors?
do any of these new mutations result in more virus shedding?
what happens when the virus becomes deadlier? how does it change to do that?
These questions are well worth addressing, but at the same time very difficult to answer meaningfully off the cuff.
Virtually every article about COVID mutations that are addressed to the layman cover the material far too superficially to even begin to speak to @Wesley_Clark 's questions. Still, a perusal of some of the better ones can at least lend a Cat-in-the-Hat level of understanding the topic: Johns Hopkins, Scientific American, BBC. All are from January of this year, and so likely don’t represent the very bleeding edge of the research into how mutations microbiologically make COVID variants more contagious, more deadly, etc. The explanations are very high-level – the spike proteins are “stickier”, antibodies are “less effective”, and so on.
But we’re still left wondering “What’s really going on way down deep?”
I tooled around a bit and found a promising publication in the journal Cell Press (cell.com). It’s titled The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity, was peer-reviewed last summer and published in July 2020. Sure, that was before news about variants really started getting any kind of traction. But an article with a title like that seemed like a good bet to help explain what’s going on at the level of individual virions, molecules, and so forth.
Then I read the summary. And I apologize to the house … but this went straight over my head:
The spike protein of SARS-CoV-2 has been undergoing mutations and is highly glycosylated. It is critically important to investigate the biological significance of these mutations. Here, we investigated 80 variants and 26 glycosylation site modifications for the infectivity and reactivity to a panel of neutralizing antibodies and sera from convalescent patients. D614G, along with several variants containing both D614G and another amino acid change, were significantly more infectious. Most variants with amino acid change at receptor binding domain were less infectious, but variants including A475V, L452R, V483A, and F490L became resistant to some neutralizing antibodies. Moreover, the majority of glycosylation deletions were less infectious, whereas deletion of both N331 and N343 glycosylation drastically reduced infectivity, revealing the importance of glycosylation for viral infectivity. Interestingly, N234Q was markedly resistant to neutralizing antibodies, whereas N165Q became more sensitive. These findings could be of value in the development of vaccine and therapeutic antibodies.
So … yeah.
I picked the word “glycosylated” from the first sentence, hoping looking that up would help me understand what the summary was covering. Wikipedia says:
Glycosylation (see also chemical glycosylation) is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor). In biology, glycosylation mainly refers in particular to the enzymatic process that attaches glycans to proteins, or other organic molecules, but actually this chemical reaction can also be non-enzymatic. The enzymatic process produces one of the fundamental biopolymers found in cells (along with DNA, RNA, and proteins). Glycosylation is a form of co-translational and post-translational modification. Glycans serve a variety of structural and functional roles in membrane and secreted proteins.
At this point … it was clear I’d have to get a lot of instruction in the field before I could even begin to helpfully address anything approaching the OP’s questions. 99 times out of 100, some Google-fu and some reading can clear up a lot of esoteric topics. However, it looks like structural virology is made of sterner stuff.
Thank you. I would’ve also accepted ‘Gods will’ as the correct answer too.