Discovery of a druggable pocket in the SARS-CoV-2 spike protein

https://medicalxpress.com/news/2020-09-discovery-druggable-pocket-sars-cov-spike.html

by virgilp • 6 years ago

87 59 6 years ago

jxcl• 6 years ago

In rhinovirus, a virus causing the common cold, a similar pocket was exploited to develop potent small molecules that bound tightly to the pocket distorting the structure of the rhinovirus, stopping its infectivity. These small molecules were successfully used as anti-viral drugs in human trials, defeating rhinovirus in the clinic.

So why isn't there a cure for the common cold? If there still isn't a cure for the common cold, why should we expect this drug target to be different?

Surely whoever wrote this article should have anticipated these questions?

(Edited to be less flippant)

gostsamo• 6 years ago

On the other hand, Oracle is mentioned twice, in case we didn't spot it the first time.

yobert• 6 years ago

The Oracle plugs are hilarious. "Enabled by Oracle high-performance cloud computing, a 3-D structure of SARS CoV-2 Spike protein was generated allowing the researchers to peer deep inside the Spike identifying its molecular composition." As if the cloud provider had anything to do with anything there.

Quarrelsome• 6 years ago

Oracle cloud must be absolute garbage given how hard its being marketed. Didn't part of the US deal with Tiktok _force_ the application into using Oracle cloud as part of the deal? I have a lot of sympathies for the TikTok devs if its not very good as its now mandatory.

Its like instead of building something good or getting techie buy in they've instead tried to lobby governments to make it mandatory for some enslaved customers.

stateofnounion• 6 years ago

Don't tug too hard at that thread, the entire narrative might unravel.

IgorPartola• 6 years ago

What does that mean?

skim_milk• 6 years ago

The common cold isn't any specific virus, it's a huge range of viruses that cause "cold" symptoms. Some coronaviruses cause "colds" as well. Common cold viruses are research targets to discover knowledge that can be weaponized to prevent pandemics.

mquirion2• 6 years ago

I almost never comment, but the answer here is simple: markets.

The common cold doesn't kill. There's almost no economic impetus for a cure. Note, I said "almost." There may be some, but there's still not enough to drive R&D in a corporate lab, and certainly not enough to drive policy in a government lab.

There are 100 other questions that would follow from science to logistic once you answer: Can we create a drug that kills infection in clinical tests?

newsbinator• 6 years ago

Surely there's a Nobel Prize in it though?

throwmeaway_pls3• 6 years ago

NyQuil’s and Alka Seltzer’s sales figures beg to differ.

epmaybe• 6 years ago

Cold can kill, viral pneumonia is real as our current pandemic can attest to. There's certainly a market to cure all sorts of viral illness. Take tamiflu as an example. Most people if they get a flu will use it once a year to reduce symptoms. Imagine a drug that would reduce all symptoms of cold that you take every time you get cold symptoms. That's potentially billions of dollars in revenue each year.

fiftyfifty• 6 years ago

I would actually argue that it should be the government's role to push the development of vaccines and drugs for treating even harmless diseases. We spend trillions of dollars on national defense in the US, when you look at the economic damage and cost in lives that the Covid-19 outbreak has cost us, the threat of disease outbreaks is every bit as damaging as a military attack, maybe even worse. If we had taken the time to develop and take all the way through the approval process a vaccine to previously encountered Coronaviruses such as SARS or MERS we would probably already have a vaccine against SARS-CoV-2 approved by the FDA and in distribution. Maybe we should be building a few less F-35s and instead be developing vaccines against otherwise harmless viruses, because you never know when a close relative of a harmless virus is going to turn into a deadly outbreak. In the US at least that seems like it should fall under the protective role of the federal government.

eximius• 6 years ago

https://journals.plos.org/plosbiology/article?id=10.1371/jou...

It might be from 2019 so there may simply have not been enough time.

whymauri2• 6 years ago

Definitely not enough time for traditional pharma to have actionable, public insights.

wittyreference3• 6 years ago

> So why isn't there a cure for the common cold?

The "common cold" refers to a benign, self-limited upper respiratory viral infection by over 200 viral subtypes, including many strains of coronavirus (causing collectively 10-15% of colds), adenovirus, enteroviruses (echovirus, coxsackievirus) rhinovirus (over 100 serotypes, collectively causing 30-50% of colds), metapneumovirus, bocavirus, influenza and parainfluenza viruses (~5% of colds each), and respiratory syncytial virus (another 5%).

I think this is general lay knowledge. Certainly, any article that uses the words "glycoprotein" is aiming at the sort of audience that knows "common cold is a syndrome caused by a buncha different viruses."

nashequilibrium• 6 years ago

When I go for the usual flu vaccine in November, how would I know which strains its protecting me against?

nradov4• 6 years ago

Not always benign. HCoV-OC43 may be roughly as deadly as SARS-CoV-2 (COVID-19) to immunologically naive patients. It is suspected to have caused a deadly worldwide pandemic in 1889. Now most people are infected during childhood and build up immunity which protects them later in life. But even today it kills immunocompromised patients.

leptons2• 6 years ago

These small molecules were successfully used as anti-viral drugs in human trials, defeating rhinovirus in the clinic.

Because it's still in trials, and not widely available, due to the long process of approving such medicines.

It still seems possible that there will be a drug that can be used to combat rhinovirus, as well as coronavirus someday, possibly sooner rather than later.

DoofusOfDeath2• 6 years ago

"Enabled by Oracle high-performance cloud computing, ..."

Anyone know why that phrase is in there? It sounds very much like product marketing, but I can't see why the researchers or this story's author would be motivated to promote Oracle.

peeters• 6 years ago

Funding: ... This work received generous support from the Oracle Higher Education and Research program to enable cryo-EM data processing using Oracle’s high-performance public cloud infrastructure (https://cloud.oracle.com/en_US/cloud-infrastructure) ...

https://science.sciencemag.org/content/early/2020/09/18/scie...

Why this summary of the work includes it prominantly, rather than in the footnotes like in the original paper, I'm not sure. Perhaps it was a condition the authors had for contributing to the article. Or perhaps it was Oracle's PR that got them the article in the first place. There is a comment from Oracle later in the article.

DoofusOfDeath2• 6 years ago

Thanks. I didn't think to look in the original sciencemag.org article.

leptons2• 6 years ago

Also possible Oracle donated the resources with the stipulation that they get mentioned in any articles about the research.

tyingq• 6 years ago

"Should I acknowledge Oracle support for my research project work, for example, in publications or on websites? Please acknowledge the “Oracle for Research” program in any publications or on websites."

https://www.oracle.com/oracle-for-research/faq.html

Apparently pushed as a requirement for the "free" Oracle cloud resources researchers can apply for.

shellac• 6 years ago

I think the medicalxpress article might have been pushed by Oracle PR?

The article itself includes Oracle in the acknowledgements, together with the various University of Bristol HPC systems used, and Archer.

gojomo• 6 years ago

Indeed, 'Medicalexpress' appears to be nothing more than reprints of press-releases about medical research. The PR teams of Bristol & Oracle probably coordinated on the authorship. This is nearly pure promotion, with a thin veneer of reporting-like language.

est31• 6 years ago

There are plenty of covid-19 vaccine trackers, but I can't find trackers for antivirals, especially novel, non-repurposed ones. E.g. what happened to compound 11a from this paper? https://science.sciencemag.org/content/368/6497/1331

The best I could find was an overview in this survey paper: https://www.sciencedirect.com/science/article/pii/S0960894X2...

whymauri2• 6 years ago

The best I have a Lancet review for repurposed drugs found via computational methods (published last week). Ignore the "AI;" most of these are just graph algorithms or vanilla neural networks. I haven't seen anything this comprehensive for novel therapeutics.

https://www.thelancet.com/action/showPdf?pii=S2589-7500%2820...

ourmandave• 6 years ago

Like drag and drop isn't complicated enough, they have to add a Druggable event?

Oracle's cloud API really is expanding.

rossdavidh4• 6 years ago

So, it's great that they're investigating, but this reads a bit too breathless to be taken entirely seriously: "stop virus in its tracks" "a potential game changer" "ground-breaking study"

...but further down: "The question now is how to turn this new knowledge against the virus itself and defeat the pandemic."

Yes, that would be the question, which is much closer to the beginning of the process of developing and producing and rolling out a new treatment, than it is to the end.

In other words, while it's great that this kind of thing is being investigated, it is extraordinarily unlikely to impact _this_ pandemic. No doubt Covid-19 will come back again, several years after this pandemic has run its course, and it's great to investigate how to be better prepared for that. But this is not going to result in a treatment fast enough that this pandemic will not already have spread to its (historically normal, typical, well-nigh-inevitable) conclusion.

nradov4• 6 years ago

COVID-19 (SARS-CoV-2) won't "come back again" because it will never go away in the first place. It has already spread so widely that it is now endemic in the worldwide human population (plus some other mammal species). Just like at least 4 other coronaviruses.

FuckButtons• 6 years ago

But we made no attempt to eliminate those corona viruses and we have, the last I checked, something like 20 vaccines in development for this one, if anything is a candidate for going the way of smallpox it’s sars cov 2, there’s too much inertia behind our efforts to stamp it out, it might just take a while.

rossdavidh4• 6 years ago

Technically, you're correct, but the 1957 flu "came back" in 1968, and again in 2009 if I recall correctly. Yes, I'm sure they were never completely gone, but at some point there are enough non-resistant people and it flares up again, and we would want to have better options for that "next time". But yes, technically, you're correct, it will never quite go away.

booleandilemma• 6 years ago

I'm left wondering, can AWS generate 3-D structures of SARS CoV-2 Spike proteins?

jmpman• 6 years ago

I’m wondering if a long strip of tape, the ability to move left or right, and the ability to write a symbol to the tape could generate 3-D structures of SARS CoV-2 Spike proteins.

0n34n7• 6 years ago

Does this mean a diet rich in linoleic acid could lessen the symptoms?

lioeters• 6 years ago

My impression is that they've only just begun to study the correlation.

Following my curiosity, I found a list of dietary sources of linoleic acid:

https://en.wikipedia.org/wiki/Linoleic_acid#Dietary_sources

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Here are the relavant passages from the article:

Unexpectedly, the research team's analysis revealed the presence of a small molecule, linoleic acid (LA), buried in a tailor-made pocket within the Spike protein.
LA is a free fatty acid, which is indispensable for many cellular functions. The human body cannot produce LA. Instead, the body absorbs this essential molecule through diet.
Intriguingly, LA plays a vital role in inflammation and immune modulation, which are both key elements of COVID-19 disease progression. LA is also needed to maintain cell membranes in the lungs so that we can breathe properly.
From other diseases we know that tinkering with LA metabolic pathways can trigger systemic inflammation, acute respiratory distress syndrome and pneumonia. These pathologies are all observed in patients suffering from severe COVID-19.
A recent study of COVID-19 patients showed markedly reduced LA levels in their sera.

Discovery of a druggable pocket in the SARS-CoV-2 spike protein

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