New Antibody Neutralizes All Known SARS-CoV-2 Variants in Lab Tests
August 18, 2022 3:46 PM   Subscribe

New antibody neutralizes all known SARS-CoV-2 variants in lab tests. An antibody from Single Human VH-rearranging mouse neutralizes all SARS-CoV-2 variants through BA.5 by inhibiting membrane fusion.

"What made SP1-77 so good at neutralizing the virus? Structural biology studies...showed that this antibody works in a unique way. [...] The SP1-77 antibody also binds to the [RBD], but in a different way that does not prevent the virus from binding to ACE2 receptors. [...] SP1-77 binds the spike protein at a site that so far has not been mutated in any variant, and it neutralizes these variants by a novel mechanism" that inhibits viral-host membrane fusion." (/r/Science discussion.)
posted by MollyRealized (23 comments total)

This post was deleted for the following reason: Poster's Request -- loup



 
I love the Twitter account In Mice to the point that I now hear "in mice" every time I read any announcement of potentially interesting new medical research. That said, I live in hope.
posted by Peach at 3:51 PM on August 18, 2022 [19 favorites]


Relevant XKCD
posted by Harvey Kilobit at 4:03 PM on August 18, 2022 [11 favorites]


Endless rounds of ERB meetings to determine exactly which box to check for research subject #10344: Little, Stuart.
posted by NoThisIsPatrick at 4:28 PM on August 18, 2022 [7 favorites]


I don't understand a lick of this, but does this mean there's actual hope this nightmare might end?
I know better to than believe, of course....
posted by jenfullmoon at 5:38 PM on August 18, 2022 [4 favorites]


Boston Children’s Hospital, with whom many of the researchers are associated, has also been in the news lately due to a barrage of threats they’ve been receiving from right wing extremists regarding their pediatric/adolescent trans health program.
posted by dephlogisticated at 5:40 PM on August 18, 2022 [15 favorites]


If Covid is a Coronavirus and the common cold is also a Coronavirus, is there a reason why a vaccine for the common cold cannot be developed?

That's something that's baffled me ever since effective Covid vaccines have been produced.
posted by chmmr at 6:28 PM on August 18, 2022 [2 favorites]


CBC ran an article today about another group's work with a broadly-neutralizing antibody fragment which was published (open-access!) in Nature Communications. I actually thought this post was about their work, until I read more closely. I'm encouraged to see how much better we're understanding SARS-CoV-2 two-plus years in.
posted by invokeuse at 6:56 PM on August 18, 2022 [6 favorites]


I don't understand a lick of this, but does this mean there's actual hope this nightmare might end?

So I hate to be negative, but as someone whose spent decades around antiviral pharmaceutical research this is evoking zero excitement in me. I mean maybe? But there's nothing inherently special that strikes me about this (outside some of the scientific novelty of some development techniques.)

For one thing, we have drugs that work in lab tests already. Some are even approved and used in human treatment! I actually think people are overly pessimistic about what these drugs actually already accomplish. But regardless of whether you believe me on that or not, I don't see any reason at this point to think this would translate better.

In addition, fusion inhibitors have generally not been sought-after anti-viral treatments. For example, despite enormous research and many successful drugs for HIV I think there was only one ever approved fusion inhibitor (Fuzeon) and it's generally of minor clinical importance--as a class, only one means no one thought it was worth trying to copy or improve. Other examples I know of for other viruses haven't performed well either; in general the knock is that it's easy to develop resistance. (I know the Harvard write up talks effusively about how this works on "all strains" but the virus hasn't had evolutionary pressure to evolve resistance to fusion inhibitors and there are no tests I saw in the paper on this point.)

I'm not super knowledgeable on the specifics of coronaviruses structural biology, so maybe there's some reason to be more excited for fusion inhibitors in this one virus. If there is I'll probably hear about it from colleagues next week and I'll update here--but don't wait for anything.

It says something about human nature--or maybe university press offices--that people always seem to get more excited about cures in a test tube or a mouse than they do about anything that gets to the point of helping treat people.
posted by mark k at 7:30 PM on August 18, 2022 [28 favorites]


I'm with jenufullmoon... I don't know what phrases like "Inhibiting Membrane Fusion" actually mean, but as someone who just missed teaching my first three days of this school year because of COVID, this gives me hope.

(And a quick shout out to the people who make the antiviral that I cannot spell. THANK YOU!! -DFM500)
posted by dfm500 at 7:31 PM on August 18, 2022 [3 favorites]


... in general the knock is that it's easy to develop resistance.

I'm no scientist but I did wonder about that just from the FPP quote. I'll reserve hope and wait to hear more from the experts, but I regret to say that I won't be surprised if mark k is right.
posted by Greg_Ace at 7:56 PM on August 18, 2022


Next up... New battery technology triples power of current generation!
posted by fairmettle at 8:09 PM on August 18, 2022 [2 favorites]


If Covid is a Coronavirus and the common cold is also a Coronavirus, is there a reason why a vaccine for the common cold cannot be developed?

Estimates vary, but many colds are due to rhinoviruses, with only a small proportion due to coronaviruses (1/5 or so) and the remainder due to RSV and other known and unknown viruses. Of those colds that are due to coronaviruses, there are four main viruses in two separate families, alpha and beta. We only actually identified some of these recently, after SARS1 caused scientists to be much more interested in coronaviruses.

Right now, we're struggling to keep up with the evolution of one coronavirus, so it would be quite difficult to keep up with four and even then we'd only cut down on colds by a relatively small amount, especially since our coronavirus vaccine would probably not be that effective at preventing infection (there would be lots of evolutionary pressure to escape immunity, just like there is driving Covid variants).

There are theories about the possibility of pan-coronaviruses vaccines (or at least pan beta-coronaviruses vaccines, which would cover Covid, SARS1, MERS and two of the common cold viruses), but it seems like that's a long way off, if it is even possible — though this is well beyond my understanding of the subject.
posted by ssg at 9:09 PM on August 18, 2022 [22 favorites]


That's so informative ssg, I was unaware of any of that. Appreciate the comprehensive reply.
posted by chmmr at 9:29 PM on August 18, 2022 [1 favorite]


in general the knock is that it's easy to develop resistance

Would a fusion inhibitor generally be used as a therapy on its own? Common HIV ARTs and PrEPs have multiple targets, and defeating them requires separate mutations that are much less likely to happen together. Enfuvirtide is used in conjunction with other antivirals, for instance.
posted by They sucked his brains out! at 10:25 PM on August 18, 2022


Would a fusion inhibitor generally be used as a therapy on its own? Common HIV ARTs and PrEPs have multiple targets, and defeating them requires separate mutations that are much less likely to happen together

Probably alone, if it worked. Even as a second agent, one that has a low barrier to resistance is less useful than one that has a high barrier.

I have a much longer answer to this if you want, but the fact that HIV is a chronic virus means it's a very different beast than an acute virus like influenza or coronavirus. With HIV you have to deal with the fact that it's got a long time to evolve resistance after you get infected; this isn't what's going on with Covid.
posted by mark k at 11:50 PM on August 18, 2022


Coming at this from a TV Tropes angle - this sounds like the beginning of a disaster movie.
posted by Bee'sWing at 3:19 AM on August 19, 2022 [2 favorites]



Coming at this from a TV Tropes angle - this sounds like the beginning of a disaster movie.


I am forever annoyed with the Will Smith I Am Legend for its clever bit of fear mongering where the engineered virus promised to cure cancer (with ensuing breathless media tour) becomes the zombie-virus.

No matter how much rigor and materialist empiricism I employ in current events, whenever I read about a "wide spectrum cure" like this I think of those laudatory scenes from that so-so movie.

I would love some kind of clearing house for news like this where we can track and collate the claims with what eventually pans out.
posted by abulafa at 4:56 AM on August 19, 2022 [3 favorites]


Probably alone, if it worked.

Enfuvirtide, for instance, is generally not prescribed on its own, to the best of my knowledge.
posted by They sucked his brains out! at 9:07 AM on August 19, 2022


I am forever annoyed with the Will Smith I Am Legend for its clever bit of fear mongering
Does the novel use the same premise? You can be annoyed with Richard Matheson, too, if it does.
posted by soelo at 10:07 AM on August 19, 2022


The Newsflesh series does the same thing with the cure for cancer, combined with the cure for the common cold, causing zombieism. However, ah, that is more based on real life than you'd think (Wired link).
“I read enough books on viruses to qualify for some kind of horrible extra-credit program, audited a bunch of courses at UC Berkeley and at the California Academy of Sciences, and then started phoning the CDC persistently and asking them horrible questions,” says McGuire in this week’s episode of the Geek’s Guide to the Galaxy podcast. (mp3 link, free).

Still, it took more than a dozen calls to work out the details of her zombie contagion. “After about the 17th time,” says McGuire, “I called and said, ‘If I did this, this, this, this, this, this and this, could I raise the dead?’ And got, ‘Don’t … don’t do that.’ And at that point, I knew I had a viable virus.”

The final iteration, Kellis-Amberlee, is actually a chimera virus resulting from the union of a genetically engineered strain of Marburg, which is a filovirus — it’s related to Ebola — meeting up with a genetically engineered coronavirus, which is one of the common cold viruses. The Marburg was designed to cure cancer, basically. It’s something that you’re supposed to get in your body and just keep there, and anytime that you develop cancerous cells, the Marburg will wake up, begin reproducing and eat them. Then the coronavirus portion, which is the “Kellis” portion, was designed as a cure for the common cold, and it’s supposed to be a pernicious infection.

Basically, it’s a shifting-antigen base. It gets into your body and it never, ever leaves, because your immune system winds up treating the Kellis infection as a part of the immune system, and doesn’t fight it off. The Kellis infection is self-replicating, and that shifting antigen means that it’s continually finding new food sources. It’s supposed to prevent other infections from getting into your body, because it’s taking up all the available space. Well, when those two viruses met, they had babies, and what you got was a shifting-antigen flu that does not leave the body under any circumstances but is capable of turning into something that converts human tissue into more of the virus. And that’s how we got Kellis-Amberlee, which makes zombies.
posted by jenfullmoon at 10:08 AM on August 19, 2022 [1 favorite]


in mice
posted by neuron at 2:38 PM on August 19, 2022 [2 favorites]


Enfuvirtide, for instance, is generally not prescribed on its own, to the best of my knowledge.

So I should do the long version of my earlier comment I guess.

HIV is a chronic viral disease. Your immune system can't clear it on its own. It can hide in reservoirs in your body. That means the drug regimen for that disease is fighting the evolution of resistance within you, personally, in response to the drugs. Hitting it with a cocktail of drugs hard is critical, because if you have even low levels of replication it will figure you how to escape the drug you want. Giving multiple drugs, all highly active on their own, and with at least two different mechanisms of action, basically knocks replication to zero and reduces the chance of "lucky" sets of mutations keeping it around. Similar observations apply to other chronic viral diseases. Even then enfurvitide (Fuzeon) isn't a front line drug, partly because of the low barrier to resistance compared to other options.

Acute viral diseases like influenza or Covid are a different kettle of fish. The viral load actually drops rapidly in treatment--I think most people who know the drugs aren't that impressive clinically would be surprised by how well they knock down the virus. And your immune system is going to clear it anyway; it clears it more quickly with the drug. The problem with acute respiratory viruses is by the time you have symptoms, or soon thereafter, you've already locked yourself into a bad situation--I mean, by their nature they do damage quickly and at that point your immune system response is contributing to the ongoing symptoms and cascading damage.

So if you have good drugs you give a single agent, virus drops by over 99% in a few days, and stragglers and resistant populations are wiped out by the immune system before they can do damage*. As treatment, if your fusion inhibitor works, then it will work on its own. If a different drug works it doesn't need the fusion inhibitor. You can't drop viral concentrations faster than you are already, really. Resistance is really a population level worry rather than an individual concern.

Maybe you'd give a cocktail of drugs anyway to slow down the evolution of resistant strains in this case, but I'd guess more likely you'd want to minimize exposure of wild type virus to novel drugs too. I think we take the latter approach with antibiotics; I don't know that people have thought much about this in the pandemic context.

But either way the main point I was trying to make with the acute/chronic distinction is you can't look at HIV or Hep C treatments and think they'd be good models for coronavirus. Of course Fuzeon is not prescribed for HIV; it's not that it's a fusion inhibitor, it's that we've never had a successful monotherapy for HIV at all!

* The asterisk here is that the "paxlovid rebound" is probably caused by a partial exception here, but it's not the normal response to antiviral treatments for acute diseases.
posted by mark k at 4:07 PM on August 19, 2022 [3 favorites]


I love the Twitter account In Mice to the point that I now hear "in mice" every time I read any announcement of potentially interesting new medical research. That said, I live in hope.

I believe the FDA is accepting animal data for the planned BA-4/5 fall booster rather than human trials. So in October probably about a fifth to a quarter of the US population will be putting mouse data to the test (because booster uptake is dropping and dropping as we move on from covid-19 without covid-19 moving on from us).

So the hope will live in you!
posted by srboisvert at 6:45 AM on August 20, 2022 [4 favorites]


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