Scientists discover receptor that blocks Covid-19 infection
sydney.edu.au
sydney.edu.au
India has just released it's intranasal sars-cov-2 vaccine for use as of a month ago (https://www.bbc.com/news/world-asia-india-64421961). I'm waiting anxiously on those large scale public results. Especially as a booster after intramuscular.
What you consistently hear from medical professionals is, "we have this proven technology, it works, the objections to it are irrational, can we please just be sensible?" So far, so good… (I'm a bit of a technocrat myself)
But why are people so afraid of vaccines in particular? There are all sorts of arguments about autism and turning frogs gay or whatever, but people are still happy to take whatever pills the doctor prescribes and hormone-enriched fast food… what makes vaccines different? It seems pretty clear that people are just afraid of needles, and from an evolutionary biology perspective, that's not irrational at all!
But "maybe we should make vaccines that won't scare people" just won't get you anywhere in the US medical establishment. Frightened patients aren't Serious Medicine.
Can't believe anyone is still pushing what's basically a shame tactic that is typically aimed at pre-adolescents. Do you feel smart or virtuous having posted that dismissive and insulting reductive view of people who don't blindly follow "THE SCIENCE" like you do? It's not the needles! It's the contents! How is that not incredibly obvious?
The same people who refuse the vaccine take unknown substances in 'supplements' which have no regulation at all. It makes no sense. Explain it.
Maybe these "same people" that you're describing exist, but they definitely aren't everyone in the set of people who refused the vaccine. They might just be the loud people.
The parent comment said 'it's not needles, don't insult me! it is because this specific vaccine is [same argument against other things which aren't outrage fodder and not addressing any of the other established vaccines which are subject to outrage]. '
It did nothing to explain away the needle aspect except 'needle phobia is uncommon', which explains nothing since a phobia is DSM classified as a 'disorder' and an 'aversion to needles' wouldn't count.
Thanks for telling me about yourself, though. It was interesting.
Not everyone who refuses the vaccine takes supplements. Your comparison is like saying "why don't you take this research chemical ('molly'), you smoke cannabis already".
I didn't ask why specifically about tylenol and supplements, I said explain why the outrage over vaccines and not other things.
The "outrage over vaccines and not other things" is in part because the mrna vaccines are new technology. People are hesitant to try something totally new on themselves.
>> The "outrage over vaccines and not other things" is in part because the mrna vaccines are new technology. People are hesitant to try something totally new on themselves.
> The MMR vaccines are not mRNA. You are completely missing the point.
Ironic, as you now choose to ignore the explanation.
If you failed to explain an implicit assumption, that's ok, as it's hard to communicate over forums. Introducing MMR (there is no reference to this in "another post") as if there was a misunderstanding on the poster's part is a non-sequitor at best and dishonest at worst.
I didn't 'introduce' anything. The grandparent post is about 'vaccines' in general. the mRNA vaccine is one of them.
The entire comment section of this article can be perused in a few minutes. Cntrl-f and I find all your comments. At this moment there are 5 (4 of which are this thread). There hasn't been some elaborate discussion that's hard to follow.
> replying to a specific part of my response to another person is not a miscommunication,
Plainly dishonest. Got it.
Let's break this down with an example:
P1: What don't you like about milks?
P2: I don't like cows.
P1: Goats are not cows.
Is P1 dishonest? If you say yes, I would disagree with you and say that you are attributing to dishonesty what is for you reading comprehension problem. If you say no then I say you are grasping at straws in order to find flaws in my argument because you cannot find a real one.
Those people maybe not being specialist cannot differentiate those remedies which are "safe" as the poster writes (which equals to "no risks or some risk of mild impact") and those which can have catastrophic impact in the relatively small set of the unlucky.
Now, however, they’re considerably less mysterious than you say they are. Several billion people have now received them, and any honest reading of the evidence from that would strongly support them being very very safe. If there were serious safety problems, we would have seen them undeniably by now.
Are you sure? Do you have numbers to show that (a critical number would be skeptical on one side and careless or trusting on the other)?
Plus intranasal influenza a vaccines have been around since the 1960s. I alternate getting intramuscular and intranasal influenza vaccines for best protection of myself and others.
I'm very hopeful for this full scale intranasal roll out of a proven intranasal vaccine for sars-cov-2. I am seriously considering a trip to India to get it as a booster to my 4x mRNA intramusculars from Moderna and BioNTech(Pfizer). I just wish they'd use nebulizers instead of a simple spray. Simple sprays work for the fluid dynamics scales involved in small animal models but as large humans we need nebulizers to get the most complete upper respiratory protection.
In short, we have to consider that other viruses like OC43 and HKU1 either do not have durable mucosal responses, or the response of the immune system is to slow for the viral dynamics of some viruses.
I’m not sure what to think about this.
A year+ ago, I would have worried that folks would treat a low-risk evaluation as a permission slip to say “the pandemic is over for me,” stop masking/etc, and thus increase the aggregate spread of the virus to folks who are high risk.
But now everyone is already doing that anyway. So yeah, it would be nice to know whether we are high risk or should just let it all go and say whatever.
I have a hard time believing that after 2 years of messaging about why people should take a vaccine that this is an “honest question”
You must have forgotten that they have been two years of communicational failures.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9832587
Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses David M. Morens, Jeffery K. Taubenberger, and Anthony S. Fauci
'Because these viruses generally do not elicit complete and durable protective immunity by themselves, they have not to date been effectively controlled by licensed or experimental vaccines. In this review, we examine challenges that have impeded development of effective mucosal respiratory vaccines ...'
Actually, the full text is:
"Viruses that replicate in the human respiratory mucosa without infecting systemically, including influenza A, SARS-CoV-2, endemic coronaviruses, RSV, and many other “common cold” viruses, cause significant mortality and morbidity and are important public health concerns. Because these viruses generally do not elicit complete and durable protective immunity by themselves, they have not to date been effectively controlled by licensed or experimental vaccines."
The authors of the paper (not just Fauci) named off a group of different viruses, not just a single one. Taken in the stated context, it should make a lot more sense to anyone who reads this stuff.
It is horrifying that the person who has lead the response to this virus for the US is a coauthor of this factually incorrect statement 3 years into the pandemic.
Not that I don't believe you, but source?
> this factually incorrect statement
Exactly which factually incorrect statement?
For full disclosure I don't vaccinate anymore (waiting until the mucosal vaccines are available). But I understand those who do, especially if they are around other people when maskless more than I am.
Here's a much older article about the original omicron (quite distinct from the BA.2 descendants we have now): https://www.cdc.gov/mmwr/volumes/71/wr/mm7109e1.htm
> The ARs among household contacts of index patients who had received a COVID-19 booster dose, of fully vaccinated index patients who completed their COVID-19 primary series within the previous 5 months, and of unvaccinated index patients were 42.7% (47 of 110), 43.6% (17 of 39), and 63.9% (69 of 108), respectively.
Basically this article doesn't show that vaccines prevent transmission. It doesn't show they don't either, although that there wasn't a more dramatic effect is a negative finding in my opinion. I wish the authors had analyzes the AR in vaccinated vs unvaccinated household contacts.
> Your eyes are exposed to the air.
I'm not the person you're responding to. Just what I do.
The mask covers the mucus membranes, except around the eyes. And I've got glasses with side-shields for the eyes. And an ASTM-III mask over the N95 mask so that I can touch and manipulate the masks without touching the breathing surface of the N95.
> You're still breathing the same air as everyone. You're still moving through clouds of expelled vapor from everyone who has walked in front of you recently. There is no hermetic seal around your nose and mouth if you wear a mask.
It's a virucidal N95, so besides the filtering also kills much of the virus that it traps. While the filtering is not 100%, the killing on top of the filtering should greatly reduce risk of infection or transmission in the unlikely event I'm infected but don't know it.
> Masks are mostly theater in everything but controlled environments.
I used to get a respiratory infection about yearly. I haven't had a contagious illness that I am aware of since January 2020.
Edit to add: And I take my daily shower after coming home for the day. I have never used a delivery service to grocery shop. I got about one month of work from home before coming back to the job part-time, and was fully back to the job by September or October of 2020.
I don't even wear a mask everywhere (not since I got vaccinated). I don't once I sit at a table at a restaurant, or at certain social functions. But somehow I still haven't gotten Covid yet (that I'm aware of at least), even after a few known exposures, so I'm guessing either it's helping at least a little bit or I had an asymptomatic case a while back.
As far as I know, though, I could still have a moderate-to-bad case of it when I get it. My parents just both got it recently, for example, (that was one of my exposures, since they were helping me clean out my flooded basement just before they got symptoms) and it took both of them over a month before they got over it, and we share genes, so in theory I should have a somewhat rough time once I get it as well.
I have masked every time I leave the house since COVID started impacting Wuhan (we had Chinese operations, so saw early impact on the business side. If you saw me masking on BART in early 2020, wave) and I haven’t gotten a single illness of any type since then.
It’s glorious.
I am often close to the only person I see all day masking, and it blows my mind why people don’t get this advantage.
Which line, what time? :) I only started riding BART in late 2019, so only had a few months of it before stopping. I'm sure I would have been ill more often than yearly if my ridership had continued.
I agree. Additionally the masks will more than pay for themselves when it comes time to cash out my accumulated sick leave when I leave this job.
Surface area of lungs: 100 m².
Surface area of eyes: 0.0004 m².
Difference: 6 orders of magnitude.
> [Covid] primarily uses a protein called the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. Lung cells have high levels of ACE2 receptors, which is why the COVID-19 virus often causes severe problems in this organ of infected people.
> Like ACE2, LRRC15 is a receptor for coronavirus, meaning the virus can bind to it. But unlike ACE2, LRRC15 does not support infection. It can, however, stick to the virus and immobilise it. In the process, it prevents other vulnerable cells from becoming infected.
> “We think it acts a bit like Velcro, molecular Velcro, in that it sticks to the spike of the virus and then pulls it away from the target cell types,” Dr Loo said.
> “Basically, the virus is coated in the other part of the Velcro, and while it's trying to get to the main receptor, it can get caught up in this mesh of LRRC15,” Mr Waller said.
Given then that this protein is synthesized by our body, and in people with less severe COVId more of this protein was found, and less in more severe cases, could mRNA injections be used to stimulate/ramp up production?
The approach mentioned in the article is a nasal spray which I suppose is easier to manufacture.
This then begs the question, could mRNA injections be used in place of traditional medication?
Probably no if the medication needs to be targeted at a specific region, yes?
Could it be that the complexity of the protein affects our capacity to produce medication for it?
Or is it that the means of administration is the main factor on how we select our approach?
With mRNA vaccines we get the cells to produce the protein. Does this imply that synthesis of the spike protein is difficult, or is it that administration is?
It's that the mechanism of production of spike (inside infected cells) parallels the mechanism of production of spike protein in a natural infection. This stimulates the immune response against spike without need for additional adjuvants.
> This then begs the question, could mRNA injections be used in place of traditional medication?
Not my specialty, but as you say targeting may be difficult. There are various lipid carriers that I believe can target certain cell types or tissues, but I don't know how well these work, and of course actually distributing them so that they will reach lung tissue is also a matter. And then how well would they work in already infected lung tissue versus just spraying the lungs with the protein?
As for the second segment. I only have more questions now. Could it be that requesting that the cells produce additional proteins of a particular kind "overloads" them or simply "asks too much" in a fashion similar to a virus?
That seems unlikely unless the administered medication is simply "too much". I wonder, is there a saturation point? ie a point where additional mRNA medication does not result in more cells producing the target protein? Seems likely.
Which then raises the question, if such a saturation point exists, then what is causing cells to explode due to virus replication? Is it that the viral particles can not escape the cell and thus they "use" pressure? If so, have we encountered a virus that "opens up" a cell without damaging it and eventually becomes parasitic to the host?
It's probably the case that when cells die prematurely, they leave traces for our immune system to trigger an issue, so not destroying the cell seems like a beneficial evolutionary advantage. Otoh, the additional code required for this is likely very "expensive".
I hope a virologist drops by and clarifies on this.
> Could it be that requesting that the cells produce additional proteins of a particular kind "overloads" them or simply "asks too much" in a fashion similar to a virus?
It could be. I believe that most of the cells that express from the mRNA vaccine do indeed die (from the immune response against them). I'm not positive about this though. In general if a cell is preferentially producing protein from a particular mRNA it doesn't have to resources left to do what is expected of it (including cellular maintenance).
> then what is causing cells to explode due to virus replication?
https://bio.libretexts.org/Bookshelves/Introductory_and_Gene... "During release, the newly-created viruses are released from the host cell, either by causing the cell to break apart, waiting for the cell to die, or by budding off through the cell membrane."
According to the video below it can be caused by crowding. I think it can also be caused by virus proteins, or an apoptotic response - programmed cell death done to hinder the viruses ability to replicate more infectious particles. Often enough the cell does not burst, but simply buds off new virus. This is still very detrimental because the cell isn't doing what it is supposed to do, instead having been hijacked to create new viruses.
> If so, have we encountered a virus that "opens up" a cell without damaging it and eventually becomes parasitic to the host?
What I'm going to say won't directly answer your question, but it will answer the question you would have had if you knew a bit more. You want to look up lytic versus lysogenic viral replication. A basic overview: https://www.khanacademy.org/science/high-school-biology/hs-h...
A more general overview of viruses linking directly to the part talking about retroviruses (the most common route of viral lysogens in animals): https://bio.libretexts.org/Courses/Mansfield_University_of_P...
A bridge like protein is created by removing parts of the spike protein through the cascade. The bridge connects the virus and the cell, and folds into itself to cause the two cells to merge.
I am not sure why it is called spike but I’d guess it’s because it looks like tiny spikes on the virus.
So when what we do with mRNA vaccines is produce the mRNA that encodes this protein, and wrap it in lipids which allow it to enter the cells and the cells manufacture it.
Now, our cells don’t naturally produce the spike protein, so this triggers our immune system to build antibodies which bind onto the proteins and render them useless, or flags for certain parts of our immune system. This results in increased production of certain cells and proteins for this specific protein.
Our immune system has the capacity to create antibodies for and bind onto all sorts of different proteins. This is because it the immune system is allowed to recombine and order its DNA. In order to avoid wrecking havoc at our own body, the immune system passes through filters which filter out proteins that would bind to the naturally occurring proteins in our body.
So natural immunity is a real thing.
I'm overburdened right now, I can't deal with any more COVID studies. But when I read the title and seeing some comments I wonder if the prior art is related.
There are still a few holdouts here on naturally acquired immunity being inferior to being given the injections but most of them hinge on a theoretical fraction of a percentage increase in potential protection from having both or upset at the prospect that someone might lie about having had covid previously and use it as an excuse to not get injected. Mostly those who rushed headfirst into mindless authoritarianism are trying to pretend they never participated in the hysteria.
This was recognized in 1905 with the Jacobson v Massachusetts decision, in the 1950s-1960s with mass polio immunization (resulting in the deaths of hundreds of children to prevent the infection of hundreds of thousands in the US), and today with required MMR vaccines to attend public schools. The view that one should be able to opt out of vaccination programs is the novel one.
[1] - https://archive.ph/FiE2r
Our [unvaccinated] 8 year-old had Covid last Spring and his symptoms lasted exactly one entire morning.
PCR swab tests were done in school on day 1, on day 2 I got a frantic phone call from his school at 7am saying "keep him home, he has Covid!".
We would not otherwise have known, since he had precisely a bit of a headache. No cough, no fever. He took a paracetamol and sat in front of the TV. By the afternoon the headache was gone.
He tested PCR positive again on day 6, so got to enjoy the full 10 days' mandatory isolation, thanks to the rules in place here at that time.
The interesting question is: what percentage of young and/or healthy people actually had a severe case of Covid? We know an awful lot of people who've had mild-to-insignificant cases...
Something between “almost nothing” and “nobody leaving the house” would be nice. At the moment we’re at “almost nothing”.
Kids of wealthy families with parents with flexible jobs will be fine. Not every kid is in a home situation like that.
Like if isolating that kid doesn't prevent any further infections, then it isn't doing any good. If isolating them for 3 days prevents a couple other kids from getting infected, it's less clear.
Using PCR tests to evaluate clearance doesn't make sense though, since they can be positive if there are fragments but no viable virus.
It's a cost and time issue. The cost of filtering snot, inoculating a culture dish of infectable cells with the filtered snot, waiting a couple of days for the cells to show signs of infection (cell swelling or bursting), and then running a PCR test on the cells in the culture dish. With high enough throughput you could probably do this for $50 or there about, and maybe three days, to verify whether they were technically still infected three days ago.
Just waiting a couple days after symptoms abate is also going to bring most of the benefit of testing for clearance.
The weekends do count, out of the 10 days they'd be out, up to 4 would be weekend days. So, really they'd have missed around 6 or 7 days of actual school. But it could also happen to fall in a public holiday, which will reduce the number of days even more. And there are school breaks throughout the year.
I find it hard to believe that many people are living such in the edge that, if their kid has to miss a week or so of school in a year their finance and jobs fully crumble.
I think you're vastly underestimating how often kids exhibit symptoms potentially consistent with Covid during a school year.
Catch C19, recover, get the sniffles in the next 2 months, get PCR tested, require a parent to take off work and the kid to sit out 10 days [possibly more than once] is not a reasonable policy IMO.
Which is why the EU issued the "recovery certificate" and put it on the same basis as a negative test, and why our schools didn't test recovered children (to clarify: were mandated not to test recovered children) after they returned to school after having Covid.
This was always true, and we never sent an obviously poorly child to daycare/preschool/school.
I've lost count of the number of times I've picked up one of our kids from daycare/preschool/school before Covid after a phone call along the lines of "your child has spiked a fever/vomited/has had an accident and should probably see a doctor".
Wasn't this typically based on common sense by the parties involved, though?
Is there any evidence this is different for Covid-19 than the vast sea of other viruses kids catch but we don’t PCR test for?
The kids around the world ended up having to take nearly two years off of school and it was shown to have a massive effect on their development.
Example had COVID, not a one-day mild illness so it might affect other children worse than the kid. I'd like to know what the negative effect of that really is, my gut feeling is that it's zero. People often make it sound like they end up insufficiently educated and socially isolated which is bs in my opinion.
Unless we are doubting the description of the parent, example had mild illness (the patient's experience of ill health) for less than one day: https://news.ycombinator.com/item?id=34752442
To a first-order approximation based on data from my three kids and their classes/schools, pretty much all the children in all the kindergarten and school classes got Covid last year. All their teachers got it, too, including the vaccinated ones.
Early last year I recall talking to my (then) 8 year-old about his best friend, who was stuck at home for a fortnight after testing positive Covid [this was before we'd all had it]:
me: "How is he?" son: "What do you mean?" me: "Is he OK?" son: "Why wouldn't he be?" me: "Is he getting better?" son: "He's not poorly, he's just positive, Daddy!"
Based on who tested postive (and indeed negative) when, it appears our 8 year-old gave it to my OH, but not to his 12 year-old brother (with whom he shares a bedroom). When my OH had it, she didn't give it to me, either, and I was testing very frequently back then due to work & travel requirements.
There is a hypothesis that the risk of catching Covid from someone may be related to the relative blood types. Based on the veeery small sample size of our immediate family it's definitely not the case that Covid always spreads quickly round a family group, despite us not having changed anything about our family routine when somone in the house was positive. We didn't send anyone to a separate bedroom, no-one wore a mask at home, and we all sat at the meal table together just as normal.
FWIW My 12 year-old and I had Covid approximately two months later, when he caught it in his school and brought it home.
According to the authors the protein binds “like velcro” effectively immobilising and preventing infection.
Symptoms would occur if sufficient cells were infected thus the second case sounds plausible to a degree.
I am not a virologist so take everything with a huge grain kf salt.
https://en.wikipedia.org/wiki/Leucine_rich_repeat_containing...
But maybe different people generate different amounts at different speeds?
https://journals.plos.org/plosbiology/article?id=10.1371/jou...
Just to cover the basics, the virus normally accesses cells by binding to ACE2.
> "The interactions between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and human host factors enable the virus to propagate infections that lead to Coronavirus Disease 2019 (COVID-19). The spike protein is the largest structural component of the virus and mediates interactions essential for infection, including with the primary angiotensin-converting enzyme 2 (ACE2) receptor."
There is a key role played in viral production by furin in ACE2-receptor-binding, which is an 'ubiquitous serine protease' in mammalian cells which plays key roles in processing hormones, growth factors, etc. and which is also exploited by many infectious diseases. This feature of Sars-CoV-2 is of course directly related to the notion that the virus was engineered, because:
> "The presence of a multibasic site (Arg-Arg-Ala-Arg) located at the S1–S2 junction, which is cleaved by furin (Fig. 1), distinguishes SARS-CoV-2 from SARS-CoV and all other known sarbecoviruses whose S protein is not cleaved by furin-like proteases during virus maturation in the infected cell. Cleavage of the S1–S2 boundary is a prerequisite for the cleavage of the S2′ site126, and both cleavage events are essential to initiate the membrane-fusion process."
https://www.nature.com/articles/s41580-021-00418-x
Accounting for the appearance of this furin cleavage site is a problem for anyone promoting a 'natural origin theory'.
Getting back to this new protein and its potential role, the other paper (first source above) seems to have a different conclusion:
> "Levels of LRRC15 were greatly elevated by inflammatory signals in the lungs of COVID-19 patients. Although infection assays demonstrated that LRRC15 alone is not sufficient to permit viral entry, we present evidence that it can modulate infection of human cells. This unexpected interaction merits further investigation to determine how SARS-CoV-2 exploits host LRRC15 and whether it could account for any of the distinctive features of COVID-19."
Their work seems to imply it might not block infection of cells, but instead enhance infection:
> "In order to examine whether LRRC15 might modulate the efficiency of viral entry into ACE2-expressing cells, we employed the naturally susceptible human lung cell line (CaLu-3) that is commonly used as a model for coronavirus infection [47]. We introduced LRRC15 ectopically to these cells to emulate the expression seen in other human lung cell populations we identified in our expression analysis. Compared to unmodified CaLu-3 cells that lack any detectable LRRC15, the expression of LRRC15 modestly enhanced viral infection"
Science is complicated, and popular media reports on recent science are often of very poor quality.
It also shows that what happens in cell culture doesn't necessarily translate to in vivo.
> Accounting for the appearance of this furin cleavage site is a problem for anyone promoting a 'natural origin theory'.
I very much think the lab leak origin is quite possible. Whether an engineered virus, or a natural chimeric virus due to bad lab practices (the Wuhan lab collected a large amount of viruses). That said it's not as if other betacoronaviruses don't have furin cleavage sites: https://www.news-medical.net/news/20230209/Assessing-the-zoo...
"The team analyzed 201 Alpha and Beta CoV strains for furin cleavage sites in their spikes. Cleavage sites in spikes were identified from 44 strains, 17 of which have bats as hosts, while 27 have other mammalian hosts. Domestic animals, including dogs, cats, cattle, horses, and rabbits, were also identified as hosts for potentially transmissible CoVs."
> Science is complicated, and popular media reports on recent science are often of very poor quality.
"The University study is one of three independent papers that reveal this specific protein’s interaction with COVID-19."
> "For coronaviruses, furin cleavage sites at the interface of the S1 and S2 domain are not unusual, being found widely in betacoronaviruses in the embeco lineage (which are considered to be of rodent origin) as well as in avian-origin gammacoronaviruses and certain feline and canine alphacoronaviruses (with an unknown origin). Furin cleavage sites are also found in certain bat-origin MERS-like merbecovirises, but not—with the exception of SARS-CoV-2—in the sarbecovirus lineage."
For such a specific motif to arise naturally seems to require a scenario like multiple infection of a host species by several different wild-type coronaviruses.
Then there's this feature:
> "So far, a viable natural origin for the SARS-CoV-2 S1–S2 site through recombination or mutation of a bat-origin virus has proved to be elusive. Of note, the S1–S2 cleavage site of SARS-CoV-2 S does not comprise the pattern found in prototypical furin cleavage sites (it is RRxR and not RxK/RR),8 making its origin enigmatic. One feature of the S1–S2 junction for the SARS-CoV-2 spike from the original outbreak is the presence of a leading proline residue, which might have promoted furin cleavage."
https://www.thelancet.com/journals/lanmic/article/PIIS2666-5...
At this point, the lab-accident-theory looks more likely than the natural-origin-theory.
> For such a specific motif to arise naturally seems to require a scenario like multiple infection of a host species by several different wild-type coronaviruses.
Two would be enough. And we know that happens already (ala XBB, deltacron, etcetera).
> > "So far, a viable natural origin for the SARS-CoV-2 S1–S2 site through recombination or mutation of a bat-origin virus has proved to be elusive. Of note, the S1–S2 cleavage site of SARS-CoV-2 S does not comprise the pattern found in prototypical furin cleavage sites (it is RRxR and not RxK/RR),8 making its origin enigmatic. One feature of the S1–S2 junction for the SARS-CoV-2 spike from the original outbreak is the presence of a leading proline residue, which might have promoted furin cleavage."
This is interesting, indeed. I wonder why an engineered site wouldn't use the prototypical cleavage motif, instead using one that might need (if I'm reading the quote correctly) a leading proline residue in order to promote cleavage?
Regarding bat lineages and host viruses, this 2019 paper seems to indicate that the other betacoronavirus lineage with the furin site, the Merbecovirus, has a different bat host range from the Sarbecovirus lineage that gave rise to Sars-CoV-2:
https://www.mdpi.com/1999-4915/11/2/174
"Compared to Sarbecovirus and Nobecovirus, the bat hosts that harbor viruses from the Merbecovirus sub-genus are more diverse. This is in line with the presence of more CoV species belonging to Merbecovirus."
(I generally trust papers on this evolutionary origin stuff published before the pandemic a bit more than those published after, as there might be less conflicts-of-interest issues).
This makes sense.
I think here's the most relevant quote from that article: "So far, no betaCoVs from the sub-genus Merbecovirus have been detected in bats of suborder Yinpterochiroptera."
While the paper does mention one member of Yangochiroptera (Chaerephon plicatus) that has been discovered infected with sarbecoviruses, it looks like there's little room for infectious overlap of merbecoviruses and sarbecoviruses (which predominantly infect Yinpterochiropterans, at least as detected as of the paper publication).
So if the SARS-CoV-2 progenitor did get its furin cleavage site from a co-infection with a merbecovirus, this would have been a really rare event indeed. At least if the co-infection happened in a bat species, and not in another animal or a human who deals with bats.
Hard to search on with only a basic understanding of what is going on.
Since the protein (LRRC15) mentioned in the article binds to the virus, making it impossible for the virus to infect the cells, it does indeed block infection.